A Study to Learn About Recifercept in Patients With Achondroplasia

A Pilot Project to Evaluate the Feasibility of Constructing a Concurrent External Control for Recifercept

The purpose of this study is to learn about the study medicine (called recifercept) in people with achondroplasia. Achondroplasia is a very rare disease and patients of achondroplasia have short arms and legs. The study will include data already collected from a recifercept clinical trial and data collected from a separate study of achondroplasia. This study will compare patient experiences and will help the investigators determine if the study medicine, recifercept, is effective.

Study Overview

• Status: Completed
• Conditions: Achondroplasia
• Intervention / Treatment: Other: Recifercept

• Study Type: Observational
• Enrollment (Actual): 248

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10017
      • Pfizer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 15 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Achondroplasia patients, aged 3 months to 11 years old with documented and confirmed genetic diagnosis of achondroplasia, who have completed at least 2 valid height and length measurement in the natural history study and have at least 6 months of follow-up data in either the natural history study or the phase 2 recifercept trial.

Description

Inclusion Criteria:

• All patients from Study C4181005 who have completed Visits 1 through 11 (at D183) will be included in this project.

To construct a concurrent external control, patients from Study C4181001 will need to meet the following inclusion criteria from Study C4181005 to be eligible for inclusion:

• Documented, confirmed genetic diagnosis of achondroplasia from historical medical records (test must have been performed at a laboratory fully accredited for genetic testing under local regulations)
• Aged ≥ 3 months to <11 years (up to the day before 11th birthday inclusive) at time of enrollment into the observational natural history study.
• Havecompleted at least 2 valid height/length measurements (at least 3 months apart)
• Assessed for Tanner stage 1 during physical examination before or at enrollment (must include assessment of breast development for females, testicular stage for males)
• Able to stand independently for height measurements (if ≥ 2 years of age at enrollment); If aged <2 years at enrollment, has a documented historical MRI brain/cervical spine performed in the previous 12 months.
• Have at least 6 months of available follow-up data after enrollment into the natural history study

Exclusion Criteria:

• Patients meeting any of the following criteria will not be included in the study:

  • Presence of severe obesity (BMI>95% percentile on Hoover-Fong BMI charts);
  • Body weight <7kg or >30kg
  • History of chronic kidney disease (CKD) or renal impairment
  • History of receipt of any treatment that are known to potentially affect growth (including oral steroids > 5 days in the last 6 months before enrollment, high dose inhaled corticosteroids (>800 mcg/day beclametasone equivalent) and medication for attention deficient hyperactivity disorder.
  • Less than 6 months since fracture or surgical procedure of any bone determined from the baseline visit date.
  • Presence of any internal guided growth plates/devices
  • History of removal of internal guided growth plates/devices within 6 months prior to enrollment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Recifercept cohort; Achondroplasia patients enrolled in the recifercept phase 2 clinical trial	Other: Recifercept; Patients received recifercept intervention in the phase 2 clinical trial
Natural history cohort; Achondroplasia patients enrolled in the achondroplasia natural history study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Height Growth at Month 3	Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.	Baseline, Month 3 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Mean Height Growth at Month 6	Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.	Baseline, Month 6 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Mean Height Growth at Month 9	Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.	Baseline, Month 9 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Mean Height Growth at Month 12	Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.	Baseline, Month 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12	Arm span to standing height or length difference was defined as absolute value (arm length [centimeter] - standing height [centimeter]). For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.	Baseline, Months 3, 6, 9, 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12	Knee height: lower segment ratio was the ratio of knee to heel length to the difference between standing height and sitting height. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.	Baseline, Months 3, 6, 9, 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12	Z-score was calculated as the difference between mean observed standing height at specified visit and mean value of reference population divided by standard deviation of reference population. Z score indicated how similar the participant was to the reference population. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.	Baseline, Months 3, 6, 9, 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Number of Participants With Achondroplasia Related Orthopedic Complications	Achondroplasia related orthopedic complications included lordosis, kyphosis, small foramen magnum: foramen magnum is slightly narrow and the spinal cord is slightly compressed at the level, foramen magnum stenosis, foramen magnum stenosis with associated c1-c2 secondary myelopathy, foramen magnum stenosis with mild posterior deformity of bulbospinal union, foramen magnum stenosis without spinal cord alteration, cervical myelomalacia; bulbar compression, marked stenosis of the foramen magnum with evident compression of bulb and bulb-medulla passage, mild foramen magnus stenosis, mild stenosis of foramen magnum, moderate to severe narrowing of the foramen magnum, severe stenosis at foramen magnum and stenosis foramen magnum.	C4181005 cohorts: 12 months; C4181001 cohort: 5 years [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Number of Participants With Other Achondroplasia Related Orthopedic Complications	Other achondroplasia related orthopedic complications included otitis media, otitis media acute, hydrocephalus and obstructive sleep apnea syndrome.	C4181005 cohorts: 12 months; C4181001 cohort: 5 years [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2022
• Primary Completion (Actual): May 16, 2023
• Study Completion (Actual): May 16, 2023

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: December 19, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): September 20, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Dwarfism; Bone Diseases, Developmental; Osteochondrodysplasias; Achondroplasia
• Other Study ID Numbers: C4181010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.