A Study Of Safety, Tolerability And Effectiveness Of Recifercept In Children With Achondroplasia

NCT04638153 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: C41810052020-001189-13
• Study Type: interventional
• Target: 60
• Locations: 8 countries
• Sites: 16

Brief Summary

Approximately 63 participants will be randomized to one of three doses to receive Recifercept either

• Low Dose
• Medium Dose
• High Dose Participants will will attend the clinic at baseline and at Day 1, 4, 8, 15, 29 \& then Month 2, 3 6, 9 \& 12. Assessments include safety, blood sampling, physical examination, vital signs, anthropometric body measurements \& patient/caregiver quality of life questionnaires Participants will received treatment with Recifercept for 12 months. All participants who complete the study and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll into an open-label extension (OLE) study. A PK cohort will include 12 participants who will randomly receive a single dose of 3 mg/kg of Phase 2 study (process 1c) formulation and a single dose of 3 mg/kg of the proposed Phase 3 (process 2) study formulation in a cross over study. Dose of the cohort could be changed due to emerging safety and efficacy data in the study.

Conditions

Achondroplasia

Keywords

Skeletal Dysplasia

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)

  Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AE is defined as an AE with onset date occurring during the on-treatment period. Relatedness to recifercept was assessed by the investigator (Yes/No).

  The first dose up to 28 to 35 days after the last dose of study intervention (13 months)

• Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12

  Height growth was defined as the ratio of observed change from baseline in standing height to the expected change from baseline in the reference population.

  Baseline, Month 3, Month 6, Month 9, and Month 12

Secondary Outcomes (21)

• Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12

  Baseline, Month 3, Month 6, Month 9, and Month 12

• Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12

  Baseline, Month 3, Month 6, Month 9, and Month 12

• Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12

  Baseline, Month 3, Month 6, Month 9, and Month 12

• Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12

  Baseline, Month 3, Month 6, Month 9, and Month 12

• Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12

  Month 3, Month 6, Month 9, and Month 12

Study Arms (5)

Low Dose

EXPERIMENTAL

Low Dose

Biological: Recifercept

Medium Dose

EXPERIMENTAL

Medium Dose

Biological: Recifercept

High Dose

EXPERIMENTAL

High Dose

Biological: Recifercept

PK Phase 2 Formulation

EXPERIMENTAL

Phase 2 formulation \[process 1c\] 3mg/kg

Biological: Recifercept

PK Phase 3 Formulation

EXPERIMENTAL

Phase 3 formulation \[process 2\] 3mg/kg

Biological: Recifercept

Interventions

Recifercept BIOLOGICAL

Recifercept

High Dose; Low Dose; Medium Dose; PK Phase 2 Formulation; PK Phase 3 Formulation

Eligibility Criteria

• Age: 3 Months - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Main cohort: Aged ≥2 years to \<11 years (up to the day before 11th birthday inclusive) at time of enrollment; or exploratory cohort: aged ≥3 months to \<2 years (up to the day before 2nd birthday inclusive) at time of enrollment
• Documented, confirmed genetic diagnosis of achondroplasia from historical medical records prior to entry into this trial (test must have been performed at a laboratory fully accredited for genetic testing under local regulations).
• Completed the C4181001 natural history study with at least 2 valid height/length measurements (at least 3 months apart) prior to enrollment in this study. One of these measurement timepoints must be within the 3 months prior to enrollment in C4181005.
• Tanner stage 1 based on investigator assessment during physical examination (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.

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 (BMI \>95th percentile on Hoover-Fong BMI charts) \[Hoover-Fong et al, 2008\].14
• Known closure of long bone growth plates (cessation of height growth).
• Body weight \<7 kg or \>30 kg.
• Moderate or severe renal impairment CrCL GFR \<60 mL/min/1.73m2 (Calculated GFR based on updated "bedside" Schwartz formula for pediatric patients (CrCL (mL/min/1.73 m2) = 0.413 \* Height (cms)/ Serum cr (mg/dL) or hepatic impairment (AST/ALT \>1.5 ULN).
• 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 beclametasone 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 investigational product for achondroplasia or that may affect growth/interpretation of growth parameters.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (16)

Ocean Sleep Medicine

Aliso Viejo, California, 92656, United States

Location

Ocean Sleep Medicine

Irvine, California, 92604, 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 Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Murdoch Children's Research Institute

Melbourne, Victoria, 3052, Australia

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Universitaire Ziekenhuizen Leuven (UZ Leuven)

Leuven, 3000, Belgium

Location

DanTrials ApS

Copenhagen NV, DK-2400, Denmark

Location

Fondazione Policlinico Universitario Agostino - Gemelli IRCCS

Roma, 00168, Italy

Location

Osaka University Hospital

Suita, Osaka, 565-0871, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

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; Mucopolysaccharidosis IV

Condition Hierarchy (Ancestors)

Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; 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

The PK study cohort was not enrolled due to early study termination, therefore, the data of the PK cohort were not collected.

Results Point of Contact

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

ClinicalTrials.gov_Inquiries@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: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Anthropometric Measurements Assessor
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: November 20, 2020
• Study Start: December 2, 2020
• Primary Completion: January 16, 2023
• Study Completion: March 27, 2023
• Last Updated: February 15, 2024
• Results First Posted: February 15, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

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