Facioscapulohumeral Muscular DystrophyPhase 2NCT03943290
Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)
A Phase 2 study testing ACE-083 in people with Facioscapulohumeral Muscular Dystrophy and Charcot-Marie-Tooth Disease, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 24 sites in 3 countries.
Trial summary
This is an open-label, multicenter, phase 2 extension study to evaluate the safety, tolerability, PK, PD, and efficacy of ACE-083 in subjects with FSHD previously enrolled in Study A083-02 and subjects with CMT1 and CMTX previously enrolled in Study A083-03. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Facioscapulohumeral Muscular Dystrophy, Charcot-Marie-Tooth Disease
- What is being tested?
- ACE-083
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 24 sitesin 3 countries
- Study dates
- 10 May 2019to 11 Mar 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Completion of treatment with study drug per protocol and completion of the end of treatment (ET) visit in Study A083-02 or Study A083-03.
- Females of childbearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy or are not naturally postmenopausal ≥ 24 consecutive months) must have negative urine pregnancy test prior to enrollment and use highly effective birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 8 weeks following the last dose of ACE-083. Hormonal birth control use must be stable for at least 14 days prior to Day 1. Males must agree to use a condom during any sexual contact with females of childbearing potential while participating in the study and for 8 weeks following the last dose of ACE-083, even if they have undergone a vasectomy. Subjects must be counseled about contraception prior to the first dose of ACE-083 and every three months thereafter during the study.
- Ability to adhere to the study visit schedule/procedures and to understand and comply with protocol requirements
- Signed written informed consent
Who cannot join
- Current/active malignancy (e.g., remission less than 5 years' duration), with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
- Co-morbidities, including symptomatic cardiopulmonary disease, significant orthopedic or neuropathic pain, or other conditions that, in the opinion of the investigator, would limit a subject's ability to complete strength and/or functional assessments
- Type 1 or type 2 diabetes mellitus
- Thyroid disorder unless condition is stable with no change in treatment for at least 4 weeks before the first dose and no expected change for duration of study
- Renal impairment (serum creatinine ≥ 2 times the upper limit of normal [ULN])
- Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≥ 3 times ULN
Show all 18Show fewer
- Increased risk of bleeding (i.e., due to hemophilia, platelet disorders, or use of any anticoagulation/platelet modifying therapies up to 2 weeks prior to Study Day 1 and for duration of study; single agent low dose aspirin [≤ 100 mg daily] is permitted)
- Severe deformity or ankle fixation that would sufficiently limit passive range of motion to affect functional assessments (TA patients only)
- Major surgery within 4 weeks prior to Study Day 1
- Chronic pharmacologic doses of systemic corticosteroids (≥ 2 weeks) within 4 weeks before Study Day 1 and for duration of study; intra-articular/topical/inhaled/intranasal physiologic doses of systemic corticosteroids are permitted
- Androgens, growth hormone, insulin or oral hormone replacement therapy within 6 months before Study Day 1 and for duration of study; topical physiologic androgen replacement is permitted. Chronic insulin therapy is permitted for diabetic FSHD patients. Oral HRT is permitted if started at least 3 months prior to receiving study drug
- Any change in medications potentially affecting muscle strength or function within 4 weeks of Study Day 1 and for duration of study (e.g., creatinine, CoQ10, systemic beta-adrenergic agonists)
- Previous exposure to any other investigational agent (not including ACE-083) potentially affecting muscle volume, muscle strength, or muscle or nerve function within 5 half-lives of last dose plus an additional 8-week washout period (or 12 weeks prior to Study Day 1 if half-life is unknown)
- Significant change in physical activity or exercise (e.g., significant increase or decrease in intensity or frequency) within 8 weeks before Study Day 1 or inability to maintain the baseline level of physical activity throughout the study
- Any condition that would prevent MRI scanning or compromise the ability to obtain a clear and interpretable scan of the treated muscles (e.g., knee/hip replacement metallic implants)
- Known active substance abuse, including alcohol
- History of sensitivity to protein pharmaceuticals
- Female that is pregnant or lactating/breast-feeding
Trial locations and contacts
24 sites in 3 countries.
24 sites in 3 countries
United States19 sites
University of Colorado
Aurora, Colorado, 80045
Brigham & Women's Hospital
Boston, Massachusetts, 02115
Carolinas Healthcare System Neurosciences Institute
Charlotte, North Carolina, 28207
Duke University Medical Center
Durham, North Carolina, 27710
University of Florida
Gainesville, Florida, 32611
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Indiana University
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of Minnesota
Minneapolis, Minnesota, 55455
Columbia University
New York, New York, 10027
University of California-Irvine
Orange, California, 92697
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University
Portland, Oregon, 97239
Virginia Commonwealth University
Richmond, Virginia, 23284
University of Rochester School of Medicine
Rochester, New York, 14642
University of California Davis Medical Center
Sacramento, California, 95817
University of Utah
Salt Lake City, Utah, 84112
Washington University School of Medicine
St Louis, Missouri, 63110
Canada3 sites
University of Calgary
Calgary, Alberta
London Health Sciences Centre
London, Ontario
Montreal Neurological Institute & Hospital
Montreal, Quebec
Spain2 sites
Hospital de la Santa Creu i Sant Pau
Barcelona
Hospital Universitario Vall d'Hebrón
Barcelona
About this study
Official title: An Open-Label Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) Previously Enrolled in Study A083-02 and in Patients With Charcot-Marie Tooth (CMT) Disease Types 1 and X Previously Enrolled in Study A083-03
This is an open-label, multicenter, phase 2 extension study to evaluate the safety, tolerability, PK, PD, and efficacy of ACE-083 in subjects with FSHD previously enrolled in Study A083-02 and subjects with CMT1 and CMTX previously enrolled in Study A083-03. This study will be conducted in two Parts: Part 1, which is a loading phase of 6 months' duration, and Part 2, the maintenance phase, which will last up to 24 months.
Read the detailed description
Part 1 (6-month, non-randomized, open-label, loading phase for subjects from A083-02 Part 1 and A083-03 Part 1) Part 1 will consist of 3 cohorts of up to 18 subjects each. Subjects enrolled in Cohorts 1a and 1b will have completed Part 1 of Study A083-02; subjects enrolled in Cohort 1c will have completed Part 1 of Study A083-03. In this loading phase, 240 mg/muscle ACE-083 will be administered bilaterally every 4 weeks (q4w) for 6 doses (6 months) into either the tibialis anterior (TA) muscle or the biceps brachii (BB) muscle, depending on the muscle injected in the previous study; subjects may not switch muscle cohort upon enrollment in this study. Subjects will participate in a screening period of up to 4 weeks before receiving the first dose of ACE-083.
Part 2 (24-month, randomized, open-label rollover maintenance phase for subjects from A083-02 Part 2, A083-03 Part 2, and A083-04 Part 1) Subjects who complete Part 1 of this study (the loading phase), Part 2 of A083-02, or Part 2 of A083-03 will enroll directly into the Part 2 open-label maintenance phase of treatment with ACE-083 and will consist of 6 cohorts of up to 23 FSHD or 29 CMT subjects each. These subjects will be randomized (1:1) to receive ACE-083, 240 mg/muscle bilaterally, either q4w or q8w. Thus, subjects enrolled in Cohorts 2a, 2b, and 2c will be FSHD TA, FSHD BB, and CMT TA treated q4w, and subjects enrolled in Cohorts 3a, 3b, and 3c will be FSHD TA, FSHD BB, and CMT TA treated q8w.
Study duration for a subject initially enrolled in Part 1 and then extended to Part 2 will be approximately 33 months, including a 1-month screening period, 6-month Part 1 loading phase, 24-month Part 2 maintenance phase, and 2-month follow-up period.
For subjects who enrolled directly into Part 2 of this study from Part 2 of Studies A083-02 and A083-03, the duration of the study will be approximately 26 months, including a 24-month maintenance phase and a 2-month follow-up period.
- Being tested
- ACE-083
- Medical subject headings
- Muscular Dystrophy, Facioscapulohumeral, Charcot-Marie-Tooth Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACE-083Drug
Recombinant fusion protein
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Cohort 1a | Experimental | ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for FSHD patients Receives: Drug: ACE-083 |
| Part 1 Cohort 1b | Experimental | ACE-083 240 mg/muscle administered bilaterally by injection into the BB muscle every 4 weeks for up to 6 doses for FSHD patients Receives: Drug: ACE-083 |
| Part 1 Cohort 1c | Experimental | ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for CMT patients Receives: Drug: ACE-083 |
| Part 2 Cohort 2a | Experimental | ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients Receives: Drug: ACE-083 |
| Part 2 Cohort 2b | Experimental | ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients Receives: Drug: ACE-083 |
| Part 2 Cohort 2c | Experimental | ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients Receives: Drug: ACE-083 |
| Part 2 Cohort 3a | Experimental | ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients Receives: Drug: ACE-083 |
| Part 2 Cohort 3b | Experimental | ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients Receives: Drug: ACE-083 |
| Part 2 Cohort 3c | Experimental | ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients Receives: Drug: ACE-083 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 2- Frequency of Adverse Events - Presence and Nature of Adverse Events (AE) During Part 2
The number of participants that had a least one Treatment Emergent Adverse Event during the Part 2 of the study. The pre-specified analysis for this outcome measure was for those participants in the part 2 cohorts of this study therefore, only data of part 2 portion of the study are reported.
Measured: From baseline to end of participation of the Part 2 portion of the study
Part 2: Frequency of Adverse Events - Presence and Nature of Grade 3 or Higher Adverse Events (AE) During the Part 2 of the Study.
The number of participants that had a least one grade 3 or higher Treatment Emergent Adverse Event during Part 2 of the study. The pre-specified analysis for this outcome measure was for those participants in the double-blind, placebo-controlled Part 2 of the study therefore, only data from the part 2 portion of the study are reported.
Measured: From baseline to the end of the part 2 portion of the study
Part 2: Change in Total Muscle Volume - Percent Change From Baseline to Day 113 in Total Muscle Volume of Injected Muscle by Magnetic Resonance Imaging (MRI) During the Part 2 Portion
The primary pharmacodynamic variable was the difference in mean percent change in total muscle volume (average of left and right side) at the first 6 months of the maintenance phase (Day 169; q4w or q8w) from the total muscle volume (average of left and right sides) at the start of the maintenance phase (or equivalently the end of the loading phase). Due to the early termination of this trial, percent change is only able to be reported as percent change from baseline to Day 113. The pre-specified analysis for this outcome measure was for those participants in the part 2 portion in cohorts with data to Day 113. Therefore, only data from these part 2 arms- 2b, 2c, 3b and 3c of the study are reported.
Measured: During the Part 2 portion of the study: Baseline to Day 113
Secondary outcomes (20)
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle:10-meter Walk/Run During Part 2 of the Study
Timing (in seconds) participants took to complete a 10-meter walk/run distance. Baseline and end of treatment visit values were used to report absolute change from baseline in functional assessment due to early termination of the trial. The pre-specified analysis for this outcome measure was for those participants with data available at baseline and at the end of treatment in part 2 of this study therefore, only data from the part 2 cohorts 2a, 2c and 3a of the study are reported.
Measured: Baseline and End of Treatment visit for Part 2 of the study
Part 2: Change in Muscle Function. Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle:10-meter Walk/Run During Part 2 of the Study
Timing (in seconds) participants took to complete a 10-meter walk/run distance. Baseline and end of treatment visit values were used to report absolute change from baseline in functional assessment due to early termination of the trial. The pre-specified analysis for this outcome measure was for those participants with data available at baseline and at the end of treatment in part 2 of this study therefore, only data from the part 2 cohorts 2a, 2c and 3a of the study are reported.
Measured: Baseline and End of Treatment visit for Part 2 of the study
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 6-minute Walk Test
During Part 2: for the 6-minute walk test, participants walked at normal pace for six minutes and the distance was measured in meters. Absolute change from baseline to end of treatment in phase 2 were reported since this trial was terminated early. Further, only part 2 cohorts 2a, 2c, and 3a had data to report for this analysis.
Measured: Baseline and End of Treatment Visit during Part 2 of the study
Part 2: Change in Muscle Function - Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle in 6-minute Walk Test
During Part 2: for the 6-minute walk test, participants walked at normal pace for six minutes and the distance was measured in meters. Absolute change from baseline to end of treatment in phase 2 were reported since this trial was terminated early. Further, only part 2 cohorts 2a, 2c, and 3c had data to report for this analysis.
Measured: Baseline and End of Treatment visit during Part 2 of the study
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 4-stair Climb Up (in Participants With FSHD Only)
During Part 2 in FSHD participants only: This is a measure (in seconds) of participants going up 4 standard stairs. Absolute Change is compared from baseline to the end of treatment visit as this trial was terminated early. As this analysis was pre-specified for FSHD patients only, data is only reported for participants with FSHD (cohorts 2a and 3a).
Measured: Baseline, End of Treatment visit during Part 2
Part 2: Change in Muscle Function - Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle in 4-stair Climb Up (in Participants With FSHD Only)
During Part 2 in FSHD participants only: This is a measure (in seconds) of participants going up 4 standard stairs. Percent Change is compared from baseline to the end of treatment visit as this trial was terminated early. As this analysis was pre-specified for FSHD patients only, data is only reported for participants with FSHD (cohorts 2a and 3a).
Measured: Baseline, End of Treatment visit during Part 2
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 4-stair Climb Down (in Participants With FSHD Only)
During Part 2 (in FSHD participants only)This is a measure (in seconds) of participants going down 4 standard stairs. Absolute Change is compared from baseline to the end of treatment visit as this trial was terminated early. As this analysis was pre-specified for FSHD patients only, data is only reported for participants with FSHD (cohorts 2a and 3a).
Measured: Baseline, End of Treatment visit during Part 2
Part 2: Change in Muscle Function. Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 4-stair Climb Down (in Patients With FSHD Only)
During Part 2 (in FSHD participants only)This is a measure (in seconds) of participants going down 4 standard stairs. Percent Change is compared from baseline to the end of treatment visit as this trial was terminated early. As this analysis was pre-specified for FSHD patients only, data is only reported for participants with FSHD (cohorts 2a and 3a).
Measured: Baseline, End of Treatment visit during Part 2
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 100-meter Timed Test
During Part 2 this measure is the timing (in seconds) to complete 100-meter walk test. Percent Change is reported from baseline to the end of treatment visit as this trial was terminated early. As this analysis was pre-specified for part 2 only, data is only reported for participants with FSHD and CMT in part 2 with data for both timepoints (cohorts 2a, 2c and 3a).
Measured: Baseline, End of Treatment visit for Part 2 of the study
Part 2: Change in Muscle Function - Percent Change From Baseline for Tibialis Anterior (TA) Muscle in 100-meter Timed Test
During Part 2 this measure is the timing (in seconds) to complete 100-meter walk test. Percent Change is reported from baseline to the end of treatment visit as this trial was terminated early. As this analysis was pre-specified for part 2 only, data is only reported for participants with FSHD and CMT in part 2 with data for both timepoints (cohorts 2a, 2c and 3a).
Measured: Baseline, End of Treatment visit, Part 2
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Biceps Brachii (BB) Muscle: Mid-level Performance of the Upper Limb (PUL) Test.
Part 2: Performance of upper limb (PUL) - Middle level elbow dimension score- Sum of the 9 items for this particular dimension (Minimum=0, Maximum = 34, with higher scores indicating increased functionality). These include: "Hand(s) to Mouth", "Hand(s) to table from lap", "Move weight on table", "Lifting light cans", "Lifting heavy cans", "Stacking light cans", "Stacking heavy cans", "Remove lid from container", and "Tearing paper". Pre-specified analysis was for absolute change in BB cohorts for FSHD participants only with Baseline and End of Treatment visit data (cohorts 2b and 3b) due to the early termination of the study. Thus, data is only reported for these two cohorts.
Measured: Baseline, End of Treatment visit during Part 2
Part 2: Change in Muscle Function - Percent Change From Baseline for Biceps Brachii (BB) Muscle in Mid-level Performance of the Upper Limb (PUL) Test
Part 2: Performance of upper limb (PUL) - Middle level elbow dimension score- Sum of the 9 items for this particular dimension (Minimum=0, Maximum = 34, with higher scores indicating increased functionality). These include: "Hand(s) to Mouth", "Hand(s) to table from lap", "Move weight on table", "Lifting light cans", "Lifting heavy cans", "Stacking light cans", "Stacking heavy cans", "Remove lid from container", and "Tearing paper". Pre-specified analysis was for percent change in BB cohorts for FSHD participants only with Baseline and End of Treatment visit data (cohorts 2b and 3b) due to the early termination of the study. Thus, data is only reported for these two cohorts.
Measured: Baseline, End of Treatment
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Biceps Brachii (BB) Muscle: Upper Level Performance of the Upper Limb (PUL) Test.
Performance of upper limb (PUL) -PUL upper level/shoulder dimension- Shoulder domain score which represents the sum of the following 4 items that the patient is asked to do on the preferred side [either right or left side identified by patient to be done on the same side for all scheduled times]: a. Largest weight patient can use to perform shoulder abduction to shoulder height (elbow to shoulder level) b. Largest weight patient can use to perform shoulder abduction above shoulder height (elbow to eye level) c. Largest weight patient can use to perform shoulder flexion to shoulder height (elbow to shoulder level) d. Largest weight patient can use to perform shoulder flexion above shoulder height (elbow to eye level) Each of the 4 components above is scored depending on the highest weight performed where scores are: 0 = Unable; 1 = Able no weights; 2 = 200 g; 3 = 500 g; 4 = 1000 g. The maximum score is 16, with 16 being highest functionality. Reportable data is for Cohort 3b only.
Measured: Baseline, End of Treatment visit during part 2 of the study
Part 2: Change in Muscle Function. Percent Change From Baseline in Functional Assessment for Biceps Brachii (BB) Muscle: Upper Level Performance of the Upper Limb (PUL) Test.
Performance of upper limb (PUL) -PUL upper level/shoulder dimension- Shoulder domain score which represents the sum of the following 4 items that the patient is asked to do on the preferred side [either right or left side identified by patient to be done on the same side for all scheduled times]: a. Largest weight patient can use to perform shoulder abduction to shoulder height (elbow to shoulder level) b. Largest weight patient can use to perform shoulder abduction above shoulder height (elbow to eye level) c. Largest weight patient can use to perform shoulder flexion to shoulder height (elbow to shoulder level) d. Largest weight patient can use to perform shoulder flexion above shoulder height (elbow to eye level) Each of the 4 components above is scored depending on the highest weight performed where scores are: 0 = Unable; 1 = Able no weights; 2 = 200 g; 3 = 500 g; 4 = 1000 g. The maximum score is 16, with 16 being highest functionality. Reportable data is for Cohort 3b only.
Measured: Baseline, End of Treatment visit during Part 2
Part 2: Change in Patient-reported Quality of Life. Absolute Change From Baseline in FSHD-health Index Total Score (FSHD-HI, in Patients With FSHD Only)
The FSHD Health Index (FSHD-HI) is a disease-specific patient reported outcome questionnaire that uses direct patient input to measure disease burden. For this index, the total score is scored from 0 to 100 with 0 representing no disease burden and 100 representing the maximum amount of disease burden in the particular domain. Pre-specified analysis was for FSHD cohorts only with absolute change in total score reported as this trial was terminated early.
Measured: Baseline, End of Treatment visit during part 2
Part2: Change in Patient-reported Quality of Life. Absolute Change From Baseline in CMT Health Index Total Score (CMT-HI, in Patients With CMT Only)
Part 2: The CMT-Health Index (CMT-HI) is a disease-specific patient reported outcome measure designed to measure patient reported disease burden during clinical trials in patients with Charcot-Marie-Tooth Disease. For this index, the total score is scored from 0 to 100 with 0 representing no disease burden and 100 representing the maximum amount of disease burden. Pre-specified analysis was for cohorts of CMT participants only and due to the early termination of this trial, the absolute change is reported for the change from Baseline to Day 113.
Measured: Baseline, Day 113 during Part 2
Part 1: ACE-083 Serum Concentration Samples Part 1-Day1, 24-hour Post-dose
Part1: ACE-083 serum concentration samples were taken on day 1, 24-hours post-dose. PK parameters of ACE-083 were not determined due to limited quantifiable concentration data. Pre-specified analysis was for part 1 cohorts only, therefore, available data is only reported for part 1 cohorts (1a, 1b and 1c). Mean and standard deviation descriptive statistics are being reported for the Day 1, 24-hour post-dose timepoint only, due to early termination of this trial.
Measured: day 1, 24 -hours post-dose in Part 1
Part1: ACE-083 Serum Concentration Samples Part 1-Day 85, 24-hour Post-dose
Part1: ACE-083 serum concentration samples were taken on day 85, 24-hours post-dose. PK parameters of ACE-083 were not determined due to limited quantifiable concentration data. Pre-specified analysis was for part 1 cohorts only, therefore, available data is only reported for part 1 cohorts (1a, 1b and 1c). Mean and standard deviation descriptive statistics are being reported for the Day 85, 24-hour post-dose timepoint only, due to early termination of this trial.
Measured: day 85, 24 -hours post-dose in Part 1
Part1: Pharmacokinetics Parameter of Time to Maximum Serum Concentration Following Administration (Tmax)
Part 1: ACE-083 concentrations ranged from 20.1 to 238.6 μg/L across FSHD and CMT cohorts with the majority of serum concentrations were below the lower limit of quantification (LLOQ) or just above LLOQ. Further, given the early termination of this trial, there were not enough samples per cohort collected at the pre-specified timeline points to be able to determine Tmax.
Measured: From baseline to End of Treatment in Part 1
Part1: Pharmacokinetics Parameter of Area Under the Plasma Concentration Versus Time Curve (AUC)
Part 1: ACE-083 concentrations ranged from 20.1 to 238.6 μg/L across FSHD and CMT cohorts with the majority of serum concentrations were below the lower limit of quantification (LLOQ) or just above LLOQ. Further, given the early termination of this trial, there were not enough samples per cohort collected at the pre-specified timeline points to be able to determine AUC.
Measured: From baseline to End of Treatment in Part 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2019
- Study start10 May 2019
- Primary completion11 Mar 2020
- Study completion11 Mar 2020
Why it stopped: Investigation of ACE-083 for use in patients with CMT and FSHD is being discontinued in this extension study as functional secondary endpoints were not achieved in the A083-023 or A083-03 trial (the parent trials).
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.
- Other trials for Facioscapulohumeral Muscular DystrophyStudies of the same condition, open and under way.
- 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
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03943290
- Sponsor's protocol ID
- A083-04
- Other IDs
- ACE-083
- Status last verified
- Sep 2022
- First submitted
- 17 Apr 2019
- Last updated
- 26 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) Previously Enrolled in Study A083-02 and in Patients With Charcot-Marie Tooth (CMT) Disease Types 1 and X Previously Enrolled in Study A083-03
- ClinicalTrials.gov ID
- NCT03943290
- Acronym / sponsor ID
- A083-04
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Investigation of ACE-083 for use in patients with CMT and FSHD is being discontinued in this extension study as functional secondary endpoints were not achieved in the A083-023 or A083-03 trial (the parent trials).
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USAIndustry (pharma, biotech, devices)
- Study start
- 10 May 2019 (actual)
- Primary completion
- 11 Mar 2020 (actual)
- Study completion
- 11 Mar 2020 (actual)
- First posted
- 9 May 2019 (actual)
- Results
- Posted 2 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, multicenter, phase 2 extension study to evaluate the safety, tolerability, PK, PD, and efficacy of ACE-083 in subjects with FSHD previously enrolled in Study A083-02 and subjects with CMT1 and CMTX previously enrolled in Study A083-03. This study will be conducted in two Parts: Part 1, which is a loading phase of 6 months' duration, and Part 2, the maintenance phase, which will last up to 24 months.
Detailed description
Part 1 (6-month, non-randomized, open-label, loading phase for subjects from A083-02 Part 1 and A083-03 Part 1) Part 1 will consist of 3 cohorts of up to 18 subjects each. Subjects enrolled in Cohorts 1a and 1b will have completed Part 1 of Study A083-02; subjects enrolled in Cohort 1c will have completed Part 1 of Study A083-03. In this loading phase, 240 mg/muscle ACE-083 will be administered bilaterally every 4 weeks (q4w) for 6 doses (6 months) into either the tibialis anterior (TA) muscle or the biceps brachii (BB) muscle, depending on the muscle injected in the previous study; subjects may not switch muscle cohort upon enrollment in this study. Subjects will participate in a screening period of up to 4 weeks before receiving the first dose of ACE-083.
Part 2 (24-month, randomized, open-label rollover maintenance phase for subjects from A083-02 Part 2, A083-03 Part 2, and A083-04 Part 1) Subjects who complete Part 1 of this study (the loading phase), Part 2 of A083-02, or Part 2 of A083-03 will enroll directly into the Part 2 open-label maintenance phase of treatment with ACE-083 and will consist of 6 cohorts of up to 23 FSHD or 29 CMT subjects each. These subjects will be randomized (1:1) to receive ACE-083, 240 mg/muscle bilaterally, either q4w or q8w. Thus, subjects enrolled in Cohorts 2a, 2b, and 2c will be FSHD TA, FSHD BB, and CMT TA treated q4w, and subjects enrolled in Cohorts 3a, 3b, and 3c will be FSHD TA, FSHD BB, and CMT TA treated q8w.
Study duration for a subject initially enrolled in Part 1 and then extended to Part 2 will be approximately 33 months, including a 1-month screening period, 6-month Part 1 loading phase, 24-month Part 2 maintenance phase, and 2-month follow-up period.
For subjects who enrolled directly into Part 2 of this study from Part 2 of Studies A083-02 and A083-03, the duration of the study will be approximately 26 months, including a 24-month maintenance phase and a 2-month follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Part 1 Cohort 1a | Experimental | Drug: ACE-083ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for FSHD patients |
| Part 1 Cohort 1b | Experimental | Drug: ACE-083ACE-083 240 mg/muscle administered bilaterally by injection into the BB muscle every 4 weeks for up to 6 doses for FSHD patients |
| Part 1 Cohort 1c | Experimental | Drug: ACE-083ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for CMT patients |
| Part 2 Cohort 2a | Experimental | Drug: ACE-083ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients |
| Part 2 Cohort 2b | Experimental | Drug: ACE-083ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients |
| Part 2 Cohort 2c | Experimental | Drug: ACE-083ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients |
| Part 2 Cohort 3a | Experimental | Drug: ACE-083ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients |
| Part 2 Cohort 3b | Experimental | Drug: ACE-083ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients |
| Part 2 Cohort 3c | Experimental | Drug: ACE-083ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Completion of treatment with study drug per protocol and completion of the end of treatment (ET) visit in Study A083-02 or Study A083-03.
- Females of childbearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy or are not naturally postmenopausal ≥ 24 consecutive months) must have negative urine pregnancy test prior to enrollment and use highly effective birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 8 weeks following the last dose of ACE-083. Hormonal birth control use must be stable for at least 14 days prior to Day 1. Males must agree to use a condom during any sexual contact with females of childbearing potential while participating in the study and for 8 weeks following the last dose of ACE-083, even if they have undergone a vasectomy. Subjects must be counseled about contraception prior to the first dose of ACE-083 and every three months thereafter during the study.
- Ability to adhere to the study visit schedule/procedures and to understand and comply with protocol requirements
- Signed written informed consent
Key exclusion criteria (18 listed)
- Current/active malignancy (e.g., remission less than 5 years' duration), with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
- Co-morbidities, including symptomatic cardiopulmonary disease, significant orthopedic or neuropathic pain, or other conditions that, in the opinion of the investigator, would limit a subject's ability to complete strength and/or functional assessments
- Type 1 or type 2 diabetes mellitus
- Thyroid disorder unless condition is stable with no change in treatment for at least 4 weeks before the first dose and no expected change for duration of study
- Renal impairment (serum creatinine ≥ 2 times the upper limit of normal [ULN])
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 |
|---|---|---|
| ACE-083Recombinant fusion protein | Drug | Part 1 Cohort 1a, Part 1 Cohort 1b, Part 1 Cohort 1c, Part 2 Cohort 2a, Part 2 Cohort 2b, Part 2 Cohort 2c, Part 2 Cohort 3a, Part 2 Cohort 3b, Part 2 Cohort 3c |
Primary outcome
Part 2- Frequency of Adverse Events - Presence and Nature of Adverse Events (AE) During Part 2
Time frame: From baseline to end of participation of the Part 2 portion of the study
The number of participants that had a least one Treatment Emergent Adverse Event during the Part 2 of the study. The pre-specified analysis for this outcome measure was for those participants in the part 2 cohorts of this study therefore, only data of part 2 portion of the study are reported.
Part 2: Frequency of Adverse Events - Presence and Nature of Grade 3 or Higher Adverse Events (AE) During the Part 2 of the Study.
Time frame: From baseline to the end of the part 2 portion of the study
The number of participants that had a least one grade 3 or higher Treatment Emergent Adverse Event during Part 2 of the study. The pre-specified analysis for this outcome measure was for those participants in the double-blind, placebo-controlled Part 2 of the study therefore, only data from the part 2 portion of the study are reported.
Part 2: Change in Total Muscle Volume - Percent Change From Baseline to Day 113 in Total Muscle Volume of Injected Muscle by Magnetic Resonance Imaging (MRI) During the Part 2 Portion
Time frame: During the Part 2 portion of the study: Baseline to Day 113
The primary pharmacodynamic variable was the difference in mean percent change in total muscle volume (average of left and right side) at the first 6 months of the maintenance phase (Day 169; q4w or q8w) from the total muscle volume (average of left and right sides) at the start of the maintenance phase (or equivalently the end of the loading phase). Due to the early termination of this trial, percent change is only able to be reported as percent change from baseline to Day 113. The pre-specified analysis for this outcome measure was for those participants in the part 2 portion in cohorts with data to Day 113. Therefore, only data from these part 2 arms- 2b, 2c, 3b and 3c of the study are reported.
20 secondary outcomes
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle:10-meter Walk/Run During Part 2 of the Study
Time frame: Baseline and End of Treatment visit for Part 2 of the study
Part 2: Change in Muscle Function. Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle:10-meter Walk/Run During Part 2 of the Study
Time frame: Baseline and End of Treatment visit for Part 2 of the study
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 6-minute Walk Test
Time frame: Baseline and End of Treatment Visit during Part 2 of the study
Part 2: Change in Muscle Function - Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle in 6-minute Walk Test
Time frame: Baseline and End of Treatment visit during Part 2 of the study
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 4-stair Climb Up (in Participants With FSHD Only)
Time frame: Baseline, End of Treatment visit during Part 2
Part 2: Change in Muscle Function - Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle in 4-stair Climb Up (in Participants With FSHD Only)
Time frame: Baseline, End of Treatment visit during Part 2
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 4-stair Climb Down (in Participants With FSHD Only)
Time frame: Baseline, End of Treatment visit during Part 2
Part 2: Change in Muscle Function. Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 4-stair Climb Down (in Patients With FSHD Only)
Time frame: Baseline, End of Treatment visit during Part 2
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 100-meter Timed Test
Time frame: Baseline, End of Treatment visit for Part 2 of the study
Part 2: Change in Muscle Function - Percent Change From Baseline for Tibialis Anterior (TA) Muscle in 100-meter Timed Test
Time frame: Baseline, End of Treatment visit, Part 2
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Biceps Brachii (BB) Muscle: Mid-level Performance of the Upper Limb (PUL) Test.
Time frame: Baseline, End of Treatment visit during Part 2
Part 2: Change in Muscle Function - Percent Change From Baseline for Biceps Brachii (BB) Muscle in Mid-level Performance of the Upper Limb (PUL) Test
Time frame: Baseline, End of Treatment
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Biceps Brachii (BB) Muscle: Upper Level Performance of the Upper Limb (PUL) Test.
Time frame: Baseline, End of Treatment visit during part 2 of the study
Part 2: Change in Muscle Function. Percent Change From Baseline in Functional Assessment for Biceps Brachii (BB) Muscle: Upper Level Performance of the Upper Limb (PUL) Test.
Time frame: Baseline, End of Treatment visit during Part 2
Part 2: Change in Patient-reported Quality of Life. Absolute Change From Baseline in FSHD-health Index Total Score (FSHD-HI, in Patients With FSHD Only)
Time frame: Baseline, End of Treatment visit during part 2
Part2: Change in Patient-reported Quality of Life. Absolute Change From Baseline in CMT Health Index Total Score (CMT-HI, in Patients With CMT Only)
Time frame: Baseline, Day 113 during Part 2
Part 1: ACE-083 Serum Concentration Samples Part 1-Day1, 24-hour Post-dose
Time frame: day 1, 24 -hours post-dose in Part 1
Part1: ACE-083 Serum Concentration Samples Part 1-Day 85, 24-hour Post-dose
Time frame: day 85, 24 -hours post-dose in Part 1
Part1: Pharmacokinetics Parameter of Time to Maximum Serum Concentration Following Administration (Tmax)
Time frame: From baseline to End of Treatment in Part 1
Part1: Pharmacokinetics Parameter of Area Under the Plasma Concentration Versus Time Curve (AUC)
Time frame: From baseline to End of Treatment in Part 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ACE-083 in people with Facioscapulohumeral Muscular Dystrophy and Charcot-Marie-Tooth Disease, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 24 sites in 3 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 4 inclusion and 18 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 26 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Canada, Spain. 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. 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 2 Jun 2021). 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?
Part 2- Frequency of Adverse Events - Presence and Nature of Adverse Events (AE) During Part 2 (time frame: From baseline to end of participation of the Part 2 portion of the study). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Sep 2022.