Duchenne Muscular DystrophyPhase 2NCT02310763
A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Duchenne Muscular Dystrophy
A Phase 2 study testing PF-06252616 in people with Duchenne Muscular Dystrophy, run by Pfizer at 66 sites in 8 countries.
Trial summary
This is a Phase 2 randomized, 2-period, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, efficacy, PK and PD of PF-06252616 administered to ambulatory boys diagnosed with Duchenne Muscular Dystrophy. Read more about this study
- Who is it for?
- Ages 6 to 15 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- PF-06252616
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 121 participants
- Where
- 66 sitesin 8 countries
- Study dates
- 24 Nov 2014to 23 Nov 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 15 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Ambulatory boys age 6 to <16 years old (at the time of randomization), diagnosed with DMD. Diagnosis must be confirmed in subject's medical history and by genetic testing obtained during routine clinical care for diagnostic purposes as reported from an appropriate regulated laboratory using a clinically validated genetic test (genetic testing is not provided by the sponsor).
- Subjects who are able to perform the 4 stair climb in > or = 0.33 but < or =1.6 stairs/second.
- Subjects must be receiving glucocorticosteroids for a minimum of 6 months prior to signing informed consent. There should be no significant change (>0.2 mg/kg) in dosage or dose regimen (not related to body weight change) for at least 3 months immediately prior to signing the informed consent and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
- Adequate hepatic and renal function on screening laboratory assessments.
- No underlying disposition for iron accumulation on screening laboratory assessments.
- Iron content estimate on the screening liver MRI is within the normal range.
Who cannot join
- Subjects with known cognitive impairment or behavioral issues that would impede the ability to follow instructions.
- History of major surgical procedure within 6 weeks of signing the informed consent or planned surgery during the study.
- Any injury which may impact functional testing. Previous injuries must be fully healed prior to consenting. Prior lower limb fractures must be fully healed and at least 3 months from injury date.
- Presence or history of other musculoskeletal or neurologic disease or somatic disorder not related to DMD including pulmonary and cardiac disease.
- Compromised cardiac function (left ventricular ejection fraction <55% as determined on a screening cardiac MRI or echocardiogram). Subjects may be receiving ACE (angiotensin converting enzyme) inhibitors or beta blockers, ARB (angiotensin II receptor antagonist) or aldosterone blocker/thiazide diuretic; however they must have initiated treatment more than 3 months prior to screening to ensure stable therapy.
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including uncontrolled hypertension), hepatic, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
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- Documented history of iron overload including hemochromatosis, beta thalassemia major, beta thalassemia intermedia or hemolytic anemia.
- Unwilling or unable (eg, metal implants, requires sedation) to undergo examination with closed MRI without sedation.
- Participation in other studies involving investigational drug(s) for a minimum of 30 days or within 5 half lives (whichever is longer) prior to signing the informed consent and/or during study participation.
- Current or prior treatment with anti-myostatin, exon skipping, nonsense mutation targeted therapies ever or more than 30 days of treatment with utrophin modifiers and treatment with utrophin modifiers within 30 days prior ot signing the informed consent and/or during study participation.
- Current or prior treatment within the past 3 months with androgens or human growth hormone.
- Current treatment with immunosuppressant therapies (other than glucocorticoid steroids), aminoglycosides (eg, gentamicin), multi vitamins with iron and iron supplements and other investigational therapies (including idebenone).
Trial locations and contacts
66 sites in 8 countries.
66 sites in 8 countries
United States30 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Kennedy Krieger Institute Out-patient center
Baltimore, Maryland, 21205
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Johns Hopkins Investigational Drug Service
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Duke University Medical Center,Lenox Baker Children's Hospital
Durham, North Carolina, 27705
Duke University, Investigational Drug Pharmacy
Durham, North Carolina, 27710
KU Clinical Research Center, Clinical and Translational Science Unit(CTSU)
Fairway, Kansas, 66205
University of Kansas-Clinical Research Center, Investigational Pharmacy
Fairway, Kansas, 66205
University of Iowa ICTS
Iowa City, Iowa, 52242
University of Kansas Medical Center, Landon Center on Aging
Kansas City, Kansas, 66160
University of Kansas Medical Center
Kansas City, Kansas, 66160
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
Ronald Reagan UCLA Pharmacy
Los Angeles, California, 90095
UCLA (David Geffen School of Medicine)
Los Angeles, California, 90095
University of Minnesota Masonic Children's Hospital
Minneapolis, Minnesota, 55455
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
University of California, Davis Medical Center
Sacramento, California, 95817
Center for Clinical and Translational Sciences
Salt Lake City, Utah, 84108
Utah Center for Advanced Imaging and Research (UCAIR)
Salt Lake City, Utah, 84108
Investigational Drug Services
Salt Lake City, Utah, 84112
University of Utah, Department of Neurology
Salt Lake City, Utah, 84112
University of Utah Medical Center
Salt Lake City, Utah, 84132
University of Utah School of Medicine
Salt Lake City, Utah, 84132
St Louis Children's Hospital
St Louis, Missouri, 63110
Shriners Hospitals for Children - Tampa
Tampa, Florida, 33612
Italy11 sites
UOC Farmacia-Istituto Gianna Gaslini, Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico
Genova, 16147
UOC Medicina Fisica Riabilitativa
Genova, 16147
UOC Neurologia Pediatrica e Malattie Muscolari
Genova, 16147
UOC Radiologia-Istituto Gianna. Gaslini, Istituto Pediatrico di Ricovero e Cura a Carattere
Genova, 16147
UOS Dipartimentale Endocrinologia Clinica Sperimentale
Genova, 16147
Dipartimento Pediatrico Universitario-Ospedaliero Endocrinologia
Rome, 00150
Farmacia Ospedaliera, IRCCS Ospedale Pediatrico Bambino Gesù, Padiglione Sant'Onofrio
Rome, 00165
Malattie Neuromuscolari e Neurodegenerative, IRCCS Ospedale Pediatrico Bambino Gesù
Rome, 00165
Ospedale Pediatrico Bambino Gesù - Centro Trial, DPUO - Padiglione Salviati
Rome, 00165
U.O.C Farmacia
Rome, 00168
U.O.C. Neuropsichiatria Infantile, Fondazione Policlinico
Rome, 00168
United Kingdom7 sites
Alder Hey Children's NHS Foundation Trust
Liverpool, L12 2AP
Alder Hey Children's NHS Foundation Trust
Liverpool, L14 5AB
Dubowitz Neuromuscular Centre Institute of Child Health
London, WC1N 3JH
Great Ormond Street Hospital
London, WC1N 3JH
Institute of Genetic Medicine, Muscle Team
Newcastle upon Tyne, NE1 3BZ
Clinical Research Facility
Newcastle upon Tyne, NE1 4LP
Royal Victoria Infirmary Research Pharmacy
Newcastle upon Tyne, NE1 4LP
Poland6 sites
Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie Apteka Szpitalna Blok F
Warsaw, 02-097
Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, I Katedra i Klinika Kardiologii
Warsaw, 02-097
Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, II Zaklad Radiologii Klinicznej
Warsaw, 02-097
Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, Klinika Neurologii
Warsaw, 02-097
Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, Laboratorium Centralne
Warsaw, 02-097
MTZ Clinical Research Sp.z o.o.
Warsaw, 02-106
Bulgaria5 sites
Clinical Densitometry and Bone Metabolic Disease Department, General and Clinical Pathology Clinic
Sofia, 1431
Hospital Pharmacy, UMHAT Alexandrovska
Sofia, 1431
Imaging Diagnostic Clinic,UMHAT Alexandrovska
Sofia, 1431
Neurology Disease Clinic,UMHAT Alexandrovska
Sofia, 1431
UMHAT Alexandrovska Cardiology Department,Internal Diseases Propaedeutic Clinic
Sofia, 1431
Canada4 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Children's Hospital- London Health Sciences Centre
London, Ontario, N6A 5W9
CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
UBC Children's and Women's Health Center of British Columbia
Vancouver, British Columbia, V6H3V4
Japan2 sites
Hyogo college of medicine hospital
Hyōgo, 663-8501
National Center of Neurology and Psychiatry
Tokyo, 187-8551
Australia1 site
Lady Cilento Children's Hospital
South Brisbane, Queensland, 4101
About this study
Official title: A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTIPLE ASCENDING DOSE STUDY TO EVALUATE THE SAFETY, EFFICACY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF-06252616 IN AMBULATORY BOYS WITH DUCHENNE MUSCULAR DYSTROPHY
This is a Phase 2 randomized, 2-period, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, efficacy, PK and PD of PF-06252616 administered to ambulatory boys diagnosed with Duchenne Muscular Dystrophy. Three intravenous (IV) dose levels will be investigated in a within subject dose escalating fashion. Subjects will be randomly assigned to 1 of 3 sequence groups for approximately 96 weeks (2 periods of 48 weeks each). In period 1, two of the sequence groups will receive PF-06252616 and one sequence group will receive placebo. In period 2, the placebo group will switch to PF-06252616 and the two remaining sequence groups will either receive placebo or PF-06252616. Efficacy will be based on an observed mean change from baseline on function (4 stair climb) of PF-06252616 as compared to the placebo at the end of period 1. Period 2 provides an opportunity to evaluate PK. Subjects will receive monthly IV infused doses of either PF-06252616 or placebo and will undergo safety evaluations (Laboratory, cardiac monitoring, physical exams, x-ray, MRI), functional evaluations (pulmonary function testing, 4 stair climb, range of motion, strength testing, Northstar Ambulatory Assessment, upper limb functional testing and the six minute walk test), pharmacokinetic testing and pharmacodynamic testing to evaluate changes in muscle volume (MRI).
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- PF-06252616, Placebo
- Keywords
- Duchenne Muscular Dystrophy, myostatin
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-06252616Biological
PF-06252616 IV Infusion, 3 dose levels (5mg/kg, 20 mg/kg and 40 mg/kg) will be investigated within each subject
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| PF-06252616 | Experimental | 3 dose levels (5mg/kg, 20mg/kg and 40 mg/kg) of IV infused PF-06252616 will be investigated within each subject Receives: Biological: PF-06252616 |
| Placebo | Placebo comparator | Matching Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator.
Measured: Study Day 1 to Week 49 visit
Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.
Measured: Study Day 1 to Week 49 visit
Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.
Measured: Study Day 1 to Week 49 visit
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology
Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils, absolute monocytes and absolute myelocytes.
Measured: Baseline to Week 49 visit
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation
Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT).
Measured: Baseline to Week 49 visit
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function
Liver function evaluation included: total/direct/indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase.
Measured: Baseline to Week 49 visit
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function
Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid.
Measured: Baseline to Week 49 visit
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes
Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate, bicarbonate, ferritin, transferrin saturation, iron, iron binding capacity and unsaturated iron binding capacity. Number of participants with iron abnormalities was reported in different age groups.
Measured: Baseline to Week 49 visit
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones
Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups.
Measured: Baseline to Week 49 visit
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry
Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, and amylase.
Measured: Baseline to Week 49 visit
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis
Urinalysis included: urine pH, qualitative urine glucose, qualitative urine ketones, qualitative urine protein, qualitative blood/hemoglobin, urine nitrite, urine leukocytes, urine RBC, urine WBC, urine granular casts, urine hyaline casts, urine urate (uric acid) acidic crystal, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam.
Measured: Baseline to Week 49 visit
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal
Number of participants with blood detected in fecal samples is presented.
Measured: Baseline to Week 49 visit
Categorical Summary of Liver Iron Accumulation by Week 49
Magnetic resonance imaging (MRI) of Liver was obtained to quantify liver iron accumulation for safety monitoring. MRIs were sent to an independent central radiology imaging facility for calculation of the average transverse relaxation rate (R2*) value which was used to monitor for iron accumulation in the liver. Number of participants meeting the following criteria is presented as follows: 1) normal: R2*<=75Hz at 1.5T or <=139 Hz at 3.0T; 2) above normal: R2*>75Hz and <=190Hz at 1.5T or R2* >139Hz and <=369Hz at 3.0T; 3) mild overload: R2*>190Hz at 1.5T or R2*>360Hz at 3.0T.
Measured: Screening, Weeks 13, 29 and 45
Number of Participants With Physical Examination Findings Reported as SAEs by Week 49
Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. A targeted nose and throat mucosal exam were also performed to monitor for any signs of mucosal telangiectasias. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which physical examination findings were reported as SAEs.
Measured: Baseline to Week 49 visit
Summary of Tanner Stage Rating by Week 49
Tanner staging was performed before the first dose of each dose escalation to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition.
Measured: Baseline, Weeks 17, 33 and 49
Number of Participants With Vital Signs Findings Reported as SAEs by Week 49
Vital signs evaluation included supine systolic and diastolic blood pressure (BP), pulse rate, and respiratory rate. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which vital signs findings were reported as SAEs.
Measured: Baseline to Week 49 visit
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49
Number of participants with ECG data meeting the following criteria are presented: 1) corrected QT interval using Fridericia's formula (QTcF interval) <450msec; 2) QTcF interval >=450 and <480msec; 3) QTcF interval >=480 and <500msec; 4) QTcF interval>=500msec; 5) QTcF interval increase from baseline<30msec; 6) QTcF interval increase from baseline >=30 and <60msec; 7) QTcF interval increase from baseline >=60msec.
Measured: Baseline to Week 49 visit
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49
The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance image (MRI) or echocardiogram. The same method of cardiac imaging was used consistently within a single participant. Cardiac MRIs were read by a central imaging vendor and echocardiograms were read locally at each site. The LVEF values measured by cardiac MRI and echocardiogram are combined in the following presentation. The analysis of covariance (ANCOVA) model was used to analyze the change from baseline for domagrozumab compared to placebo on LVEF. The baseline result, age, use of angiotensin receptor blocker (ARB)/beta blocker/angiotensin converting enzyme (ACE) inhibitor and treatment were included as fixed effects in the model.
Measured: Baseline to Week 49 visit
Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49
Bone mineral density (BMD) was evaluated by Dual energy X-ray Absorptiometry (DXA). The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was "below the expected range for age". If the Z-score was above -2 standard deviations, the result was "within the expected range for age".
Measured: Screening and Week 49
Bone Age to Chronological Age Ratio by Week 49
Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date-date of birth+1)/365.25.
Measured: Screening, Weeks 17, 33 and 49
Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. AEs of suicide ideation or behavior were determined by the investigator.
Measured: Baseline to Week 49 visit
Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49
The 4SC quantified the time required for a participant to ascend 4 standard steps. Mixed effect model for repeated measures (MMRM) was used to analyze the change from baseline on 4SC for domagrozumab compared to placebo. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Secondary outcomes (52)
Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49
FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49
The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49
ROM was evaluated by using goniometry to evaluate the loss of motion in the ankles. MMRM was used to analyze the change from baseline on ROM for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49
The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline to Week 49 on 4SC for Participants in Sequence 3 Compared to the Natural History Control Group
The 4SC quantified the time required for a participant to ascend 4 standard steps. MMRM was used to analyze the change from baseline on 4SC for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG (Cooperative International Neuromuscular Research Group) natural history database. Participants who met the following requirements at baseline and had evaluable 4SC data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.
Measured: Baseline, Week 49
Change From Baseline to Week 97 on 4SC for Participants in Sequence 1 Compared to the Natural History Control Group
The 4SC quantified the time required for a participant to ascend 4 standard steps. MMRM was used to analyze the change from baseline on 4SC for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 4SC data on Week 97 were included in this group: 1) age: 6 to <16 years; 2) treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.
Measured: Baseline, Week 97
Change From Baseline to Week 49 on FVC for Participants in Sequence 3 Compared to the Natural History Control Group
FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for the natural history control group compared to placebo group (Sequence 3). MMRM was used to analyze the change from baseline on FVC for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable FVC data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.
Measured: Baseline, Week 49
Change From Baseline to Week 97 on FVC for Participants in Sequence 1 Compared to the Natural History Control Group
FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable FVC data on Week 97 were included in this group: 1) age: 6 to <16 years; 2) treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.
Measured: Baseline, Week 97
Change From Baseline to Week 49 on NSAA for Participants in Sequence 3 Compared to the Natural History Control Group
The NSAA is a 17-item test that measured gross motor function. A total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline on NSAA for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on the using natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable NSAA data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.
Measured: Baseline, Week 49
Change From Baseline to Week 97 on NSAA for Participants in Sequence 1 Compared to the Natural History Control Group
The NSAA is a 17-item test that measured gross motor function. The total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline on NSAA for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable NSAA data on Week 97 were included in this group: 1) age: 6 to <16 years; 2) treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.
Measured: Baseline, Week 97
Change From Baseline to Week 49 on 6MWD for Participants in Sequence 3 Compared to the Natural History Control Group
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 6MWD data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.
Measured: Baseline, Week 49
Change From Baseline to Week 97 on 6MWD for Participants in Sequence 1 Compared to the Natural History Control Group
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 6MWD data on Week 97 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.
Measured: Baseline, Week 97
Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets
The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 17
Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets
The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds.MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 33
Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets
The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 49
Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets
FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 17
Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets
FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 33
Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets
FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 49
Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets
The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 17
Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets
The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 33
Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets
The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 49
Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets
The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline .The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 17
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets
The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items).Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline.The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 33
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets
The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items).Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline.The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 49
Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 17
Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 33
Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Week 49
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds)
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC <3.5 seconds are presented below.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds)
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC >=3.5 seconds and <=8 seconds are presented below.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds)
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC >8 seconds are presented below.
Measured: Baseline, Weeks 17, 33 and 49
Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49
The whole thigh muscle volume was measured by the proton density weighted sequence with magnetic resonance imaging (MRI) which was used to segment the entire thigh region into 3 primary regions for volumetric measure including 1) muscle; 2) inter/intra-muscular fat, 3) subcutaneous fat. MMRM was used to analyze the percent change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49
The thigh muscle volume index was derived from the thigh muscle volume measurements as the fraction of total thigh tissue that was the lean muscle. MMRM was used to analyze the percent change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Measured: Baseline, Weeks 17, 33 and 49
Change From Baseline in Whole Thigh Muscle Volume Through Week 97
The whole thigh muscle volume was measured by the proton density weighted sequence with magnetic resonance imaging (MRI) which was used to segment the entire thigh region into 3 primary regions for volumetric measure including 1) muscle; 2) inter/intra-muscular fat, 3) subcutaneous fat.
Measured: Baseline, Weeks 17, 33, 49 and 97
Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97
The thigh muscle volume index was derived from the thigh muscle volume measurements as the fraction of total thigh tissue that was the lean muscle.
Measured: Baseline, Weeks 17, 33, 49 and 97
Concentration of Growth Differentiation Factor 8 (GDF-8) at Time 0 (Pre-dose),(C0(GDF-8) )
GDF-8, also called myostatin, is the target of domagrozumab. C0(GDF-8) was observed directly from data.
Measured: Predose on Day 1 of Week 1
Trough Serum Concentration of GDF-8 (Ctrough,(GDF-8)) for Participants Receiving Domagrozumab in Period 1
GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data.
Measured: Every 4 weeks on dosing day (at predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 48
Ctrough,(GDF-8) for Participants of Sequence 3 in Period 2
GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data.
Measured: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 49 to Week 96
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab
Ctrough was observed directly from data.
Measured: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3
Maximum Serum Concentration (Cmax) of Domagrozumab
Cmax was observed directly from data.
Measured: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3
Time for Cmax (Tmax) of Domagrozumab
Tmax was observed directly from the data.
Measured: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3
Terminal Half-life (t1/2) of Domagrozumab for Participants in Sequence 2 After the Last Dose of Domagrozumab
t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Participants in Sequence 2 received the last dose of domagrozumab at Week 45.
Measured: At predose, end of 2-hour infusion and 6 hours since start of infusion at Week 45
Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab
The dosing interval tau was 672 hours (4 weeks). AUCtau was obtained by linear/log trapezoidal method. The AUCtau was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits.
Measured: At predose, end of 2-hour infusion,6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45
Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab
Cav was calculated by AUCtau/tau. The Cav was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits.
Measured: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45
Clearance (CL) of Domagrozumab
CL was calculated by Dose/AUCtau. The CL was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits.
Measured: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 13, 29 and 45
Volume of Distribution at Steady State (Vss) of Domagrozumab for Participants in Sequence 2 Required for Additional PK Assessment
Vss was calculated by CL*MRT, where MRT was the mean residence time. Vss was assessed to fully characterize PK data.
Measured: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Week 45
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97
The criterion for positive result of ADA samples was ADA titer >=1.88.
Measured: Baseline, every 4 weeks from Week 5 to Week 97 visit or early termination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2014 (estimated)
- Study start24 Nov 2014
- Primary completion30 Apr 2018
- Study completion23 Nov 2018
Why it stopped: Termination Date 30AUG2018: Reason for termination: Lack of Efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02310763
- Sponsor's protocol ID
- B5161002
- Other IDs
- 2014-002072-92, 2014
- Status last verified
- Oct 2020
- First submitted
- 4 Nov 2014
- Last updated
- 7 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Publications
Sherlock SP, McCrady A, Palmer J, Aghamolaey H, Ahlgren A, Widholm P, Dahlqvist Leinhard O, Karlsson M. Relationship Between Quantitative Magnetic Resonance Imaging Measures and Functional Changes in Patients With Duchenne Muscular Dystrophy. Muscle Nerve. 2025 Mar;71(3):343-352. doi: 10.1002/mus.28321. Epub 2024 Dec 23.
PubMed 39713935Sherlock SP, Palmer J, Wagner KR, Abdel-Hamid HZ, Tian C, Mah JK, Muntoni F, Guglieri M, Butterfield RJ, Charnas L, Marraffino S. Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy. Sci Rep. 2022 Nov 5;12(1):18762. doi: 10.1038/s41598-022-23072-5.
PubMed 36335191Wojciechowski J, Purohit VS, Harnisch LO, Dua P, Tan B, Nicholas T. Population PK and PD Analysis of Domagrozumab in Pediatric Patients with Duchenne Muscular Dystrophy. Clin Pharmacol Ther. 2022 Dec;112(6):1291-1302. doi: 10.1002/cpt.2747. Epub 2022 Oct 4.
PubMed 36104012Muntoni F, Guglieri M, Mah JK, Wagner KR, Brandsema JF, Butterfield RJ, McDonald CM, Mayhew AG, Palmer JP, Marraffino S, Charnas L, Mercuri E. Novel approaches to analysis of the North Star Ambulatory Assessment (NSAA) in Duchenne muscular dystrophy (DMD): Observations from a phase 2 trial. PLoS One. 2022 Aug 23;17(8):e0272858. doi: 10.1371/journal.pone.0272858. eCollection 2022.
PubMed 35998119Sherlock SP, Palmer J, Wagner KR, Abdel-Hamid HZ, Bertini E, Tian C, Mah JK, Kostera-Pruszczyk A, Muntoni F, Guglieri M, Brandsema JF, Mercuri E, Butterfield RJ, McDonald CM, Charnas L, Marraffino S. Quantitative magnetic resonance imaging measures as biomarkers of disease progression in boys with Duchenne muscular dystrophy: a phase 2 trial of domagrozumab. J Neurol. 2022 Aug;269(8):4421-4435. doi: 10.1007/s00415-022-11084-0. Epub 2022 Apr 8.
PubMed 35396602Wagner KR, Guglieri M, Ramaiah SK, Charnas L, Marraffino S, Binks M, Vaidya VS, Palmer J, Goldstein R, Muntoni F. Safety and disease monitoring biomarkers in Duchenne muscular dystrophy: results from a Phase II trial. Biomark Med. 2021 Oct;15(15):1389-1396. doi: 10.2217/bmm-2021-0222. Epub 2021 Sep 17.
PubMed 34533053Sherlock SP, Zhang Y, Binks M, Marraffino S. Quantitative muscle MRI biomarkers in Duchenne muscular dystrophy: cross-sectional correlations with age and functional tests. Biomark Med. 2021 Jun;15(10):761-773. doi: 10.2217/bmm-2020-0801. Epub 2021 Jun 22.
PubMed 34155911Wagner KR, Abdel-Hamid HZ, Mah JK, Campbell C, Guglieri M, Muntoni F, Takeshima Y, McDonald CM, Kostera-Pruszczyk A, Karachunski P, Butterfield RJ, Mercuri E, Fiorillo C, Bertini ES, Tian C, Statland J, Sadosky AB, Purohit VS, Sherlock SP, Palmer JP, Binks M, Charnas L, Marraffino S, Wong BL. Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Neuromuscul Disord. 2020 Jun;30(6):492-502. doi: 10.1016/j.nmd.2020.05.002. Epub 2020 May 19.
PubMed 32522498
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTIPLE ASCENDING DOSE STUDY TO EVALUATE THE SAFETY, EFFICACY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF-06252616 IN AMBULATORY BOYS WITH DUCHENNE MUSCULAR DYSTROPHY
- ClinicalTrials.gov ID
- NCT02310763
- Acronym / sponsor ID
- B5161002
- Conditions
- Duchenne Muscular Dystrophy
- Keywords
- Duchenne Muscular Dystrophy, myostatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Termination Date 30AUG2018: Reason for termination: Lack of Efficacy
- Enrolment
- 121 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 24 Nov 2014 (actual)
- Primary completion
- 30 Apr 2018 (actual)
- Study completion
- 23 Nov 2018 (actual)
- First posted
- 8 Dec 2014 (estimated)
- Results
- Posted 23 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2 randomized, 2-period, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, efficacy, PK and PD of PF-06252616 administered to ambulatory boys diagnosed with Duchenne Muscular Dystrophy. Three intravenous (IV) dose levels will be investigated in a within subject dose escalating fashion. Subjects will be randomly assigned to 1 of 3 sequence groups for approximately 96 weeks (2 periods of 48 weeks each). In period 1, two of the sequence groups will receive PF-06252616 and one sequence group will receive placebo. In period 2, the placebo group will switch to PF-06252616 and the two remaining sequence groups will either receive placebo or PF-06252616. Efficacy will be based on an observed mean change from baseline on function (4 stair climb) of PF-06252616 as compared to the placebo at the end of period 1. Period 2 provides an opportunity to evaluate PK. Subjects will receive monthly IV infused doses of either PF-06252616 or placebo and will undergo safety evaluations (Laboratory, cardiac monitoring, physical exams, x-ray, MRI), functional evaluations (pulmonary function testing, 4 stair climb, range of motion, strength testing, Northstar Ambulatory Assessment, upper limb functional testing and the six minute walk test), pharmacokinetic testing and pharmacodynamic testing to evaluate changes in muscle volume (MRI).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PF-06252616 | Experimental | Biological: PF-062526163 dose levels (5mg/kg, 20mg/kg and 40 mg/kg) of IV infused PF-06252616 will be investigated within each subject |
| Placebo | Placebo comparator | Drug: PlaceboMatching Placebo |
Who may qualify
- Ages
- 6 to 15 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Ambulatory boys age 6 to <16 years old (at the time of randomization), diagnosed with DMD. Diagnosis must be confirmed in subject's medical history and by genetic testing obtained during routine clinical care for diagnostic purposes as reported from an appropriate regulated laboratory using a clinically validated genetic test (genetic testing is not provided by the sponsor).
- Subjects who are able to perform the 4 stair climb in > or = 0.33 but < or =1.6 stairs/second.
- Subjects must be receiving glucocorticosteroids for a minimum of 6 months prior to signing informed consent. There should be no significant change (>0.2 mg/kg) in dosage or dose regimen (not related to body weight change) for at least 3 months immediately prior to signing the informed consent and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
- Adequate hepatic and renal function on screening laboratory assessments.
- No underlying disposition for iron accumulation on screening laboratory assessments.
Key exclusion criteria (12 listed)
- Subjects with known cognitive impairment or behavioral issues that would impede the ability to follow instructions.
- History of major surgical procedure within 6 weeks of signing the informed consent or planned surgery during the study.
- Any injury which may impact functional testing. Previous injuries must be fully healed prior to consenting. Prior lower limb fractures must be fully healed and at least 3 months from injury date.
- Presence or history of other musculoskeletal or neurologic disease or somatic disorder not related to DMD including pulmonary and cardiac disease.
- Compromised cardiac function (left ventricular ejection fraction <55% as determined on a screening cardiac MRI or echocardiogram). Subjects may be receiving ACE (angiotensin converting enzyme) inhibitors or beta blockers, ARB (angiotensin II receptor antagonist) or aldosterone blocker/thiazide diuretic; however they must have initiated treatment more than 3 months prior to screening to ensure stable therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF-06252616PF-06252616 IV Infusion, 3 dose levels (5mg/kg, 20 mg/kg and 40 mg/kg) will be investigated within each subject | Biological | PF-06252616 |
| Placebo | Drug | Placebo |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49
Time frame: Study Day 1 to Week 49 visit
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator.
Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49
Time frame: Study Day 1 to Week 49 visit
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.
Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49
Time frame: Study Day 1 to Week 49 visit
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology
Time frame: Baseline to Week 49 visit
Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils, absolute monocytes and absolute myelocytes.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation
Time frame: Baseline to Week 49 visit
Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT).
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function
Time frame: Baseline to Week 49 visit
Liver function evaluation included: total/direct/indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function
Time frame: Baseline to Week 49 visit
Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes
Time frame: Baseline to Week 49 visit
Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate, bicarbonate, ferritin, transferrin saturation, iron, iron binding capacity and unsaturated iron binding capacity. Number of participants with iron abnormalities was reported in different age groups.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones
Time frame: Baseline to Week 49 visit
Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry
Time frame: Baseline to Week 49 visit
Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, and amylase.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis
Time frame: Baseline to Week 49 visit
Urinalysis included: urine pH, qualitative urine glucose, qualitative urine ketones, qualitative urine protein, qualitative blood/hemoglobin, urine nitrite, urine leukocytes, urine RBC, urine WBC, urine granular casts, urine hyaline casts, urine urate (uric acid) acidic crystal, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal
Time frame: Baseline to Week 49 visit
Number of participants with blood detected in fecal samples is presented.
Categorical Summary of Liver Iron Accumulation by Week 49
Time frame: Screening, Weeks 13, 29 and 45
Magnetic resonance imaging (MRI) of Liver was obtained to quantify liver iron accumulation for safety monitoring. MRIs were sent to an independent central radiology imaging facility for calculation of the average transverse relaxation rate (R2*) value which was used to monitor for iron accumulation in the liver. Number of participants meeting the following criteria is presented as follows: 1) normal: R2*<=75Hz at 1.5T or <=139 Hz at 3.0T; 2) above normal: R2*>75Hz and <=190Hz at 1.5T or R2* >139Hz and <=369Hz at 3.0T; 3) mild overload: R2*>190Hz at 1.5T or R2*>360Hz at 3.0T.
Number of Participants With Physical Examination Findings Reported as SAEs by Week 49
Time frame: Baseline to Week 49 visit
Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. A targeted nose and throat mucosal exam were also performed to monitor for any signs of mucosal telangiectasias. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which physical examination findings were reported as SAEs.
Summary of Tanner Stage Rating by Week 49
Time frame: Baseline, Weeks 17, 33 and 49
Tanner staging was performed before the first dose of each dose escalation to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition.
Number of Participants With Vital Signs Findings Reported as SAEs by Week 49
Time frame: Baseline to Week 49 visit
Vital signs evaluation included supine systolic and diastolic blood pressure (BP), pulse rate, and respiratory rate. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which vital signs findings were reported as SAEs.
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49
Time frame: Baseline to Week 49 visit
Number of participants with ECG data meeting the following criteria are presented: 1) corrected QT interval using Fridericia's formula (QTcF interval) <450msec; 2) QTcF interval >=450 and <480msec; 3) QTcF interval >=480 and <500msec; 4) QTcF interval>=500msec; 5) QTcF interval increase from baseline<30msec; 6) QTcF interval increase from baseline >=30 and <60msec; 7) QTcF interval increase from baseline >=60msec.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49
Time frame: Baseline to Week 49 visit
The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance image (MRI) or echocardiogram. The same method of cardiac imaging was used consistently within a single participant. Cardiac MRIs were read by a central imaging vendor and echocardiograms were read locally at each site. The LVEF values measured by cardiac MRI and echocardiogram are combined in the following presentation. The analysis of covariance (ANCOVA) model was used to analyze the change from baseline for domagrozumab compared to placebo on LVEF. The baseline result, age, use of angiotensin receptor blocker (ARB)/beta blocker/angiotensin converting enzyme (ACE) inhibitor and treatment were included as fixed effects in the model.
Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49
Time frame: Screening and Week 49
Bone mineral density (BMD) was evaluated by Dual energy X-ray Absorptiometry (DXA). The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was "below the expected range for age". If the Z-score was above -2 standard deviations, the result was "within the expected range for age".
Bone Age to Chronological Age Ratio by Week 49
Time frame: Screening, Weeks 17, 33 and 49
Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date-date of birth+1)/365.25.
Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49
Time frame: Baseline to Week 49 visit
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. AEs of suicide ideation or behavior were determined by the investigator.
Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
The 4SC quantified the time required for a participant to ascend 4 standard steps. Mixed effect model for repeated measures (MMRM) was used to analyze the change from baseline on 4SC for domagrozumab compared to placebo. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
52 secondary outcomes
Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline to Week 49 on 4SC for Participants in Sequence 3 Compared to the Natural History Control Group
Time frame: Baseline, Week 49
Change From Baseline to Week 97 on 4SC for Participants in Sequence 1 Compared to the Natural History Control Group
Time frame: Baseline, Week 97
Change From Baseline to Week 49 on FVC for Participants in Sequence 3 Compared to the Natural History Control Group
Time frame: Baseline, Week 49
Change From Baseline to Week 97 on FVC for Participants in Sequence 1 Compared to the Natural History Control Group
Time frame: Baseline, Week 97
Change From Baseline to Week 49 on NSAA for Participants in Sequence 3 Compared to the Natural History Control Group
Time frame: Baseline, Week 49
Change From Baseline to Week 97 on NSAA for Participants in Sequence 1 Compared to the Natural History Control Group
Time frame: Baseline, Week 97
Change From Baseline to Week 49 on 6MWD for Participants in Sequence 3 Compared to the Natural History Control Group
Time frame: Baseline, Week 49
Change From Baseline to Week 97 on 6MWD for Participants in Sequence 1 Compared to the Natural History Control Group
Time frame: Baseline, Week 97
Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets
Time frame: Baseline, Week 17
Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets
Time frame: Baseline, Week 33
Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets
Time frame: Baseline, Week 49
Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets
Time frame: Baseline, Week 17
Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets
Time frame: Baseline, Week 33
Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets
Time frame: Baseline, Week 49
Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets
Time frame: Baseline, Week 17
Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets
Time frame: Baseline, Week 33
Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets
Time frame: Baseline, Week 49
Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets
Time frame: Baseline, Week 17
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets
Time frame: Baseline, Week 33
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets
Time frame: Baseline, Week 49
Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets
Time frame: Baseline, Week 17
Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets
Time frame: Baseline, Week 33
Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets
Time frame: Baseline, Week 49
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds)
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds)
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds)
Time frame: Baseline, Weeks 17, 33 and 49
Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49
Time frame: Baseline, Weeks 17, 33 and 49
Change From Baseline in Whole Thigh Muscle Volume Through Week 97
Time frame: Baseline, Weeks 17, 33, 49 and 97
Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97
Time frame: Baseline, Weeks 17, 33, 49 and 97
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39713935Sherlock SP, McCrady A, Palmer J, Aghamolaey H, Ahlgren A, Widholm P, Dahlqvist Leinhard O, Karlsson M. Relationship Between Quantitative Magnetic Resonance Imaging Measures and Functional Changes in Patients With Duchenne Muscular Dystrophy. Muscle Nerve. 2025 Mar;71(3):343-352. doi: 10.1002/mus.28321. Epub 2024 Dec 23.
- Derived from this study: PubMed 36335191Sherlock SP, Palmer J, Wagner KR, Abdel-Hamid HZ, Tian C, Mah JK, Muntoni F, Guglieri M, Butterfield RJ, Charnas L, Marraffino S. Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy. Sci Rep. 2022 Nov 5;12(1):18762. doi: 10.1038/s41598-022-23072-5.
- Derived from this study: PubMed 36104012Wojciechowski J, Purohit VS, Harnisch LO, Dua P, Tan B, Nicholas T. Population PK and PD Analysis of Domagrozumab in Pediatric Patients with Duchenne Muscular Dystrophy. Clin Pharmacol Ther. 2022 Dec;112(6):1291-1302. doi: 10.1002/cpt.2747. Epub 2022 Oct 4.
- Derived from this study: PubMed 35998119Muntoni F, Guglieri M, Mah JK, Wagner KR, Brandsema JF, Butterfield RJ, McDonald CM, Mayhew AG, Palmer JP, Marraffino S, Charnas L, Mercuri E. Novel approaches to analysis of the North Star Ambulatory Assessment (NSAA) in Duchenne muscular dystrophy (DMD): Observations from a phase 2 trial. PLoS One. 2022 Aug 23;17(8):e0272858. doi: 10.1371/journal.pone.0272858. eCollection 2022.
- Derived from this study: PubMed 35396602Sherlock SP, Palmer J, Wagner KR, Abdel-Hamid HZ, Bertini E, Tian C, Mah JK, Kostera-Pruszczyk A, Muntoni F, Guglieri M, Brandsema JF, Mercuri E, Butterfield RJ, McDonald CM, Charnas L, Marraffino S. Quantitative magnetic resonance imaging measures as biomarkers of disease progression in boys with Duchenne muscular dystrophy: a phase 2 trial of domagrozumab. J Neurol. 2022 Aug;269(8):4421-4435. doi: 10.1007/s00415-022-11084-0. Epub 2022 Apr 8.
- Derived from this study: PubMed 34533053Wagner KR, Guglieri M, Ramaiah SK, Charnas L, Marraffino S, Binks M, Vaidya VS, Palmer J, Goldstein R, Muntoni F. Safety and disease monitoring biomarkers in Duchenne muscular dystrophy: results from a Phase II trial. Biomark Med. 2021 Oct;15(15):1389-1396. doi: 10.2217/bmm-2021-0222. Epub 2021 Sep 17.
- Derived from this study: PubMed 34155911Sherlock SP, Zhang Y, Binks M, Marraffino S. Quantitative muscle MRI biomarkers in Duchenne muscular dystrophy: cross-sectional correlations with age and functional tests. Biomark Med. 2021 Jun;15(10):761-773. doi: 10.2217/bmm-2020-0801. Epub 2021 Jun 22.
- Derived from this study: PubMed 32522498Wagner KR, Abdel-Hamid HZ, Mah JK, Campbell C, Guglieri M, Muntoni F, Takeshima Y, McDonald CM, Kostera-Pruszczyk A, Karachunski P, Butterfield RJ, Mercuri E, Fiorillo C, Bertini ES, Tian C, Statland J, Sadosky AB, Purohit VS, Sherlock SP, Palmer JP, Binks M, Charnas L, Marraffino S, Wong BL. Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Neuromuscul Disord. 2020 Jun;30(6):492-502. doi: 10.1016/j.nmd.2020.05.002. Epub 2020 May 19.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
66 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PF-06252616 in people with Duchenne Muscular Dystrophy, run by Pfizer at 66 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 66 sites in United States, Italy, United Kingdom, Poland, Bulgaria and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 (time frame: Study Day 1 to Week 49 visit). The study lists 22 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02310763, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2020.