AchondroplasiaPhase 2NCT05116046
Continuation Study of Long-term Safety, Tolerability, Pharmacokinetics and Efficacy of Recifercept in Achondroplasia
A Phase 2 study testing Recifercept in people with Achondroplasia, run by Pfizer at 14 sites in 7 countries.
Trial summary
All participants who completed the prior study to assess long-term safety, tolerability, pharmacokinetics and efficacy, and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll in this open-label extension (OLE) study for up to an additional 24 months of… Read more about this study
- Who is it for?
- Ages 15 months to 12 years
- Conditions the study is for
- Achondroplasia
- What is being tested?
- Recifercept
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 14 sitesin 7 countries
- Study dates
- 24 Dec 2021to 30 Mar 2023
- 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 15 months to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male and female participants between the ages of >15 months to <12 years inclusive, at Visit 1 (Screen 1).
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests lifestyle considerations and other study procedures.
- Completed the C4181005 Phase 2 study.
- Able to stand independently for height measurements (if ≥2 years of age at enrollment).
Who cannot join
- Presence of co-morbid conditions or circumstances that, in the opinion of the investigator, would affect interpretation of growth data or ability to complete the trial procedures.
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- Presence of severe obesity (body mass index (BMI) >95th percentile on Hoover-Fong BMI charts) [Hoover-Fong et al, 2008].
- Known closure of long bone growth plates (cessation of height growth).
- Body weight >45 kg.
- History of hypersensitivity to study intervention or any excipients.
Show all 15Show fewer
- History of any prior treatment with human growth hormone or related products (including insulin-like growth factor 1 [IGF-1]).
- History of receipt of any treatment that are known to potentially affect growth (including oral steroids >5 days in the last 6 months, high dose inhaled corticosteroids (>800 mcg/day beclometasone equivalent) and medication for attention deficit hyperactivity disorder).
- History of limb lengthening surgery (defined as distraction osteogenesis/Ilizarov/callostasis technique following submetaphyseal osteotomy to extend bone length).
- Any limb lengthening/corrective orthopaedic surgery planned at any point during the trial period.
- Less than 6 months since fracture or surgical procedure of any bone determined from the screening visit date.
- Presence of any internal guided growth plates/devices.
- History of removal of internal guided growth plates/devices within less than 6 months.
- History of receipt of any other (except recifercept) investigational product for achondroplasia or that may affect growth/interpretation of growth parameters.
- History of receipt of an investigational drug (not for achondroplasia/growth affecting) within the last 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
Trial locations and contacts
14 sites in 7 countries.
14 sites in 7 countries
United States6 sites
Texas Childrens Hospital/Baylor College of Medicine
Houston, Texas, 77030
Ocean Sleep Medicine
Irvine, California, 92604
Long Beach Memorial Medical Center
Long Beach, California, 90806
MemorialCare Sleep Disorders Center at Long Beach Memorial Medical Center
Long Beach, California, 90806
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502
Nemours Children's Hospital, Delaware
Wilmington, Delaware, 19803
Belgium2 sites
Antwerp University Hospital
Edegem, 2650
UZ Leuven - Center of Human Genetics
Leuven, Flanders, 3000
Denmark2 sites
Bispebjerg Hospital
Copenhagen, 2100
Bispebjerg Hospital
Copenhagen, 2400
Australia1 site
Murdoch Children's Research Institute
Parkville, Victoria, 3052
Italy1 site
Fondazione Policlinico Universitario Agostino Gemelli IRCCS Università Cattolica del Sacro Cuore
Roma, 00168
Portugal1 site
Centro Hospitalar e Universitário de Coimbra - Hospital Pediátrico
Coimbra, 3000-602
About this study
Official title: A PHASE 2 OPEN LABEL EXTENSION STUDY TO ASSESS THE LONG-TERM SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF RECIFERCEPT IN CHILDREN WITH ACHONDROPLASIA
All participants who completed the prior study to assess long-term safety, tolerability, pharmacokinetics and efficacy, and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll in this open-label extension (OLE) study for up to an additional 24 months of treatment.
Approximately 63 participants will be offered to continue at the previously received dose of Recifercept either
Read more
Low Dose Medium Dose High Dose
or at the therapeutic dose once it is identified.
Participants will attend the clinic monthly for 24 months. Assessments include safety, blood sampling, physical examination, vital signs, anthropometric body measurements \& patient/caregiver quality of life questionnaires.
- Conditions
- Achondroplasia
- Being tested
- Recifercept
- Keywords
- achondroplasia, dwarfism, bone diseases, development, bone diseases, Musculoskeletal Diseases, Osteochondrodysplasias, Genetic Diseases, Inborn, Skeletal Dysplasia
- Medical subject headings
- Achondroplasia, Dwarfism, Bone Diseases, Musculoskeletal Diseases, Osteochondrodysplasias, Genetic Diseases, Inborn, Mucopolysaccharidosis IV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ReciferceptBiological
Recifercept
| Study group | Role | What they receive |
|---|---|---|
| Low Dose | Experimental | Low Dose Receives: Biological: Recifercept |
| Medium Dose | Experimental | Medium Dose Receives: Biological: Recifercept |
| High Dose | Experimental | High Dose Receives: Biological: Recifercept |
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), Serious Adverse Events (SAEs) and Severe AEs
An AE was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start emerges. SAE was an AE resulting in any of the following outcomes or considered medically significant: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or birth defect. Severe AEs were AEs that were medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated disabling, limiting self-care activities of daily living.
Measured: From first dose of study drug up to 28 days after last dose of study drug (maximum up to 11 months)
Change From Baseline in Height at Month 24
Height was measured using anthropometric measurements. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.
Measured: Baseline, Month 24
Secondary outcomes (14)
Clearance (CL/F) of Recifercept
Clearance of a drug was a measure of the rate at which a drug is metabolised or eliminated by normal biological processes.
Measured: Predose on Day 91, 181, 271, 361 and 451.
Change From Baseline in Sitting Height to Standing Height Ratio at Months 3, 6, 9
Sitting height to standing height ratio was calculated based upon the anthropometric measurements. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.
Measured: Baseline and Months 3, 6, 9
Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9
Height and length difference was calculated with anthropometric measurements. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.
Measured: Baseline and Months 3, 6, 9
Change From Baseline in Knee Height to Lower Segment Ratio at Months 3, 6, 9
Knee height was defined as the distance from the sole of the foot to the most anterior surface of the femoral condyles of the thigh (medial being more anterior), with the ankle and knee each flexed to a 90-degree angle. Lower segment of the leg included tibia and foot height
Measured: Baseline and Months 3, 6, 9
Change From Baseline in Occipito-Frontal Circumference at Months 3, 6, 9
Occipito-frontal circumference was measured by anthropometric measurements. It was measured over the most prominent part on the back of the head (occiput) and just above the eyebrows (supraorbital ridges).
Measured: Baseline and Months 3, 6, 9
Change From Baseline in Occipito-Frontal Distance to Occipito-mid-Face Measurements Ratio at Months 3, 6, 9
Occipito-frontal circumference was measured by anthropometric measurements. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.
Measured: Baseline, Months 3, 6, 9
Change From Baseline in Z-Score for Occipito-frontal Circumference, Arm Span, Sitting Height and Skull Morphology at Months 3, 6, 9
The Z-score described how many standard deviations a given measurement lies above or below a size or age-specific population mean. A Z-score above the population mean indicates a positive value, whereas a Z-score below the population mean indicates a negative value. The greater the deviation of the Z-score from zero (in a positive or negative direction), the greater the magnitude of deviation from the mean.
Measured: Baseline, Months 3, 6, 9
Change From Baseline in Fixed Flexion Angles at Elbow at Months 3, 6, 9
Fixed Flexion Angles was measured by anthropometric measurements. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.
Measured: Baseline, Months 3, 6, 9
Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 9
Measured: Baseline, Months 3, 6, 9
Change From Baseline in Waist to Chest Circumference Ratio at Months 3, 6, 9
Measured: Baseline, Months 3, 6, 9
Number of Participants With Clinically Meaningful Findings in Laboratory Test Parameters Through the Study
Laboratory parameters that were assessed included lymphocytes, neutrophils, eosinophils, monocytes and potassium. Clinically significant abnormal laboratory findings were determined based on investigator's decision.
Measured: From baseline up to end of study/early termination (for a maximum duration of 11 months)
Number of Participants With Clinically Significant Findings in Vital Signs Through the Study
Absolute values and changes from baseline in supine systolic and diastolic blood pressure, oral temperature, and pulse rate were planned to be summarized by treatment in accordance with the sponsor reporting standards. Clinically significant abnormal laboratory findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Measured: From baseline up to end of study/early termination (for a maximum duration of 11 months)
Number of Participants With Clinically Significant Findings in Physical Examination Through the Study
A complete physical examination included cardiovascular, respiratory, gastrointestinal systems, and skin. Height and weight will also be measured and recorded as part of the anthropometric measurements collected. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.
Measured: From baseline up to end of study/early termination (for a maximum duration of 11 months)
Number of Participants With Positive Anti-Drug Antibodies (ADA)
Measured: From Month 3 up to end of study/early termination (up to Month 11)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2021
- Study start24 Dec 2021
- Primary completion16 Dec 2022
- Study completion30 Mar 2023
Why it stopped: The study was terminated due to lack of efficacy at any of the tested doses on 18th November 2022. The decision to terminate the study is not related to a safety concern.
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 AchondroplasiaStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 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
- NCT05116046
- Sponsor's protocol ID
- C4181008
- Other IDs
- 2021-003149-39
- Status last verified
- Feb 2024
- First submitted
- 18 Oct 2021
- Last updated
- 8 Feb 2024
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 2 OPEN LABEL EXTENSION STUDY TO ASSESS THE LONG-TERM SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF RECIFERCEPT IN CHILDREN WITH ACHONDROPLASIA
- ClinicalTrials.gov ID
- NCT05116046
- Acronym / sponsor ID
- C4181008
- Conditions
- Achondroplasia
- Keywords
- achondroplasia, dwarfism, bone diseases, development, bone diseases, Musculoskeletal Diseases, Osteochondrodysplasias, Genetic Diseases, Inborn, Skeletal Dysplasia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to lack of efficacy at any of the tested doses on 18th November 2022. The decision to terminate the study is not related to a safety concern.
- Enrolment
- 35 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 24 Dec 2021 (actual)
- Primary completion
- 16 Dec 2022 (actual)
- Study completion
- 30 Mar 2023 (actual)
- First posted
- 10 Nov 2021 (actual)
- Results
- Posted 8 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
All participants who completed the prior study to assess long-term safety, tolerability, pharmacokinetics and efficacy, and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll in this open-label extension (OLE) study for up to an additional 24 months of treatment.
Approximately 63 participants will be offered to continue at the previously received dose of Recifercept either
Low Dose Medium Dose High Dose
or at the therapeutic dose once it is identified.
Participants will attend the clinic monthly for 24 months. Assessments include safety, blood sampling, physical examination, vital signs, anthropometric body measurements \& patient/caregiver quality of life questionnaires.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low Dose | Experimental | Biological: ReciferceptLow Dose |
| Medium Dose | Experimental | Biological: ReciferceptMedium Dose |
| High Dose | Experimental | Biological: ReciferceptHigh Dose |
Who may qualify
- Ages
- 15 months to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Male and female participants between the ages of >15 months to <12 years inclusive, at Visit 1 (Screen 1).
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests lifestyle considerations and other study procedures.
- Completed the C4181005 Phase 2 study.
- Able to stand independently for height measurements (if ≥2 years of age at enrollment).
Key exclusion criteria (15 listed)
- Presence of co-morbid conditions or circumstances that, in the opinion of the investigator, would affect interpretation of growth data or ability to complete the trial procedures.
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- Presence of severe obesity (body mass index (BMI) >95th percentile on Hoover-Fong BMI charts) [Hoover-Fong et al, 2008].
- Known closure of long bone growth plates (cessation of height growth).
- Body weight >45 kg.
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 |
|---|---|---|
| ReciferceptRecifercept | Biological | High Dose, Low Dose, Medium Dose |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Severe AEs
Time frame: From first dose of study drug up to 28 days after last dose of study drug (maximum up to 11 months)
An AE was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start emerges. SAE was an AE resulting in any of the following outcomes or considered medically significant: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or birth defect. Severe AEs were AEs that were medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated disabling, limiting self-care activities of daily living.
Change From Baseline in Height at Month 24
Time frame: Baseline, Month 24
Height was measured using anthropometric measurements. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.
14 secondary outcomes
Clearance (CL/F) of Recifercept
Time frame: Predose on Day 91, 181, 271, 361 and 451.
Change From Baseline in Sitting Height to Standing Height Ratio at Months 3, 6, 9
Time frame: Baseline and Months 3, 6, 9
Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9
Time frame: Baseline and Months 3, 6, 9
Change From Baseline in Knee Height to Lower Segment Ratio at Months 3, 6, 9
Time frame: Baseline and Months 3, 6, 9
Change From Baseline in Occipito-Frontal Circumference at Months 3, 6, 9
Time frame: Baseline and Months 3, 6, 9
Change From Baseline in Occipito-Frontal Distance to Occipito-mid-Face Measurements Ratio at Months 3, 6, 9
Time frame: Baseline, Months 3, 6, 9
Change From Baseline in Z-Score for Occipito-frontal Circumference, Arm Span, Sitting Height and Skull Morphology at Months 3, 6, 9
Time frame: Baseline, Months 3, 6, 9
Change From Baseline in Fixed Flexion Angles at Elbow at Months 3, 6, 9
Time frame: Baseline, Months 3, 6, 9
Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 9
Time frame: Baseline, Months 3, 6, 9
Change From Baseline in Waist to Chest Circumference Ratio at Months 3, 6, 9
Time frame: Baseline, Months 3, 6, 9
Number of Participants With Clinically Meaningful Findings in Laboratory Test Parameters Through the Study
Time frame: From baseline up to end of study/early termination (for a maximum duration of 11 months)
Number of Participants With Clinically Significant Findings in Vital Signs Through the Study
Time frame: From baseline up to end of study/early termination (for a maximum duration of 11 months)
Number of Participants With Clinically Significant Findings in Physical Examination Through the Study
Time frame: From baseline up to end of study/early termination (for a maximum duration of 11 months)
Number of Participants With Positive Anti-Drug Antibodies (ADA)
Time frame: From Month 3 up to end of study/early termination (up to Month 11)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Related trials for Achondroplasia
Enrolling by invitationPhase 2
Extension Study of Infigratinib in Children With Achondroplasia (ACH)
Achondroplasia
RecruitingPhase 2/3
Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia
Achondroplasia
Active, not recruitingPhase 2
A Clinical Trial to Evaluate Efficacy and Safety of Navepegritide in Adolescents (12 - 18 Years of Age) With Achondroplasia.
Achondroplasia
Active, not recruitingPhase 3
Evaluate the Efficacy and Safety of KK8398 in Patients With Achondroplasia（AOBA Study）
Achondroplasia
RecruitingPhase 2
A Study of TYRA-300 in Children With Achondroplasia: BEACH301
Achondroplasia
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
14 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Recifercept in people with Achondroplasia, run by Pfizer at 14 sites in 7 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 15 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 8 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Belgium, Denmark, Australia, Italy and 2 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. 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 8 Feb 2024). 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), Serious Adverse Events (SAEs) and Severe AEs (time frame: From first dose of study drug up to 28 days after last dose of study drug (maximum up to 11 months)). The study lists 2 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 8 Feb 2024.