Continuation Study of Long-term Safety, Tolerability, Pharmacokinetics and Efficacy of Recifercept in Achondroplasia

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

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 Overview

• Status: Terminated
• Conditions: Achondroplasia
• Intervention / Treatment: Biological: Recifercept

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Murdoch Children's Research Institute
• Belgium
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
  • Vlaams - Gewest
    • Leuven, Vlaams - Gewest, Belgium, 3000
      • UZ Leuven - Center of Human Genetics
• Denmark
  • Copenhagen, Denmark, 2100
    • Bispebjerg Hospital
  • Kobenhavn, Denmark, 2400
    • Bispebjerg Hospital
• Italy
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS Universita Cattolica del Sacro Cuore
• Portugal
  • Coimbra, Portugal, 3000-602
    • Centro Hospitalar e Universitário de Coimbra - Hospital Pediátrico
• Spain
  • Alava
    • Vitoria - Gasteiz, Alava, Spain, 01008
      • Hospital Vithas San Jose
• United States
  • California
    • Irvine, California, United States, 92604
      • Ocean Sleep Medicine
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Long Beach, California, United States, 90806
      • MemorialCare Sleep Disorders Center at Long Beach Memorial Medical Center
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Children's Hospital, Delaware
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Childrens Hospital/Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.
• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose	Biological: Recifercept; Recifercept
Experimental: Medium Dose	Biological: Recifercept; Recifercept
Experimental: High Dose	Biological: Recifercept; Recifercept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Baseline, Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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	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).	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.	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.	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.	Baseline, Months 3, 6, 9
Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 9		Baseline, Months 3, 6, 9
Change From Baseline in Waist to Chest Circumference Ratio at Months 3, 6, 9		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.	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.	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.	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)		From Month 3 up to end of study/early termination (up to Month 11)

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): December 24, 2021
• Primary Completion (Actual): December 16, 2022
• Study Completion (Actual): March 30, 2023

Study Registration Dates

• First Submitted: October 18, 2021
• First Submitted That Met QC Criteria: November 3, 2021
• First Posted (Actual): November 10, 2021

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: bone diseases; Musculoskeletal Diseases; achondroplasia; dwarfism; bone diseases, development; Osteochondrodysplasias; Genetic Diseases, Inborn; Skeletal Dysplasia
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Dwarfism; Bone Diseases, Developmental; Osteochondrodysplasias; Achondroplasia
• Other Study ID Numbers: C4181008; 2021-003149-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No