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

NCT05116046 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: C41810082021-003149-39
• Study Type: interventional
• Target: 35
• Locations: 7 countries
• Sites: 14

Brief 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 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.

Conditions

Achondroplasia

Keywords

achondroplasia; dwarfism; bone diseases, development; bone diseases; Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn; Skeletal Dysplasia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (14)

• Clearance (CL/F) of Recifercept

  Predose on Day 91, 181, 271, 361 and 451.

• Change From Baseline in Sitting Height to Standing Height Ratio at Months 3, 6, 9

  Baseline and Months 3, 6, 9

• Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9

  Baseline and Months 3, 6, 9

• Change From Baseline in Knee Height to Lower Segment Ratio at Months 3, 6, 9

  Baseline and Months 3, 6, 9

• Change From Baseline in Occipito-Frontal Circumference at Months 3, 6, 9

  Baseline and Months 3, 6, 9

Study Arms (3)

Low Dose

EXPERIMENTAL

Low Dose

Biological: Recifercept

Medium Dose

EXPERIMENTAL

Medium Dose

Biological: Recifercept

High Dose

EXPERIMENTAL

High Dose

Biological: Recifercept

Interventions

Recifercept BIOLOGICAL

Recifercept

High Dose; Low Dose; Medium Dose

Eligibility Criteria

• Age: 15 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (14)

Ocean Sleep Medicine

Irvine, California, 92604, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

MemorialCare Sleep Disorders Center at Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Nemours Children's Hospital, Delaware

Wilmington, Delaware, 19803, United States

Location

Texas Childrens Hospital/Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

UZ Leuven - Center of Human Genetics

Leuven, Flanders, 3000, Belgium

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Bispebjerg Hospital

Copenhagen, 2100, Denmark

Location

Bispebjerg Hospital

Copenhagen, 2400, Denmark

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS Università Cattolica del Sacro Cuore

Roma, 00168, Italy

Location

Centro Hospitalar e Universitário de Coimbra - Hospital Pediátrico

Coimbra, 3000-602, Portugal

Location

Hospital Vithas San Jose

Vitoria-Gasteiz, Alava, 01008, Spain

Location

Related Links

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

MeSH Terms

Conditions

Achondroplasia; Dwarfism; Bone Diseases; Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn; Mucopolysaccharidosis IV

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Data was not collected for efficacy endpoints as study was terminated early based on sponsor discretion due to lack of efficacy at any of the tested doses. The decision to terminate the study was not related to a safety concern.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquires@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2021
• First Posted: November 10, 2021
• Study Start: December 24, 2021
• Primary Completion: December 16, 2022
• Study Completion: March 30, 2023
• Last Updated: February 8, 2024
• Results First Posted: February 8, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

ES (1); PT (1); DK (2); US (6); AU (1); BE (2); IT (1)