Clinical trial NCT05116046: Continuation Study of Long-term Safety, Tolerability, Pharmacokinetics and Efficacy of Recifercept in Achondroplasia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Achondroplasia
Keywords: achondroplasia
dwarfism
bone diseases, development
bone diseases
Musculoskeletal Diseases
Osteochondrodysplasias
Genetic Diseases, Inborn
Skeletal Dysplasia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-11-10
Enrollment: 35
Sex: ALL
Minimum age (years): 15
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Severe AEs
timeFrame: From first dose of study drug up to 28 days after last dose of study drug (maximum up to 11 months)
measure: Change From Baseline in Height at Month 24
timeFrame: Baseline, Month 24
Secondary outcomes:
measure: Clearance (CL/F) of Recifercept
timeFrame: Predose on Day 91, 181, 271, 361 and 451.
measure: Change From Baseline in Sitting Height to Standing Height Ratio at Months 3, 6, 9
timeFrame: Baseline and Months 3, 6, 9
measure: Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9
timeFrame: Baseline and Months 3, 6, 9
measure: Change From Baseline in Knee Height to Lower Segment Ratio at Months 3, 6, 9
timeFrame: Baseline and Months 3, 6, 9
measure: Change From Baseline in Occipito-Frontal Circumference at Months 3, 6, 9
timeFrame: Baseline and Months 3, 6, 9
measure: Change From Baseline in Occipito-Frontal Distance to Occipito-mid-Face Measurements Ratio at Months 3, 6, 9
timeFrame: Baseline, Months 3, 6, 9
measure: Change From Baseline in Z-Score for Occipito-frontal Circumference, Arm Span, Sitting Height and Skull Morphology at Months 3, 6, 9
timeFrame: Baseline, Months 3, 6, 9
measure: Change From Baseline in Fixed Flexion Angles at Elbow at Months 3, 6, 9
timeFrame: Baseline, Months 3, 6, 9
measure: Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 9
timeFrame: Baseline, Months 3, 6, 9
measure: Change From Baseline in Waist to Chest Circumference Ratio at Months 3, 6, 9
timeFrame: Baseline, Months 3, 6, 9
measure: Number of Participants With Clinically Meaningful Findings in Laboratory Test Parameters Through the Study
timeFrame: From baseline up to end of study/early termination (for a maximum duration of 11 months)
measure: Number of Participants With Clinically Significant Findings in Vital Signs Through the Study
timeFrame: From baseline up to end of study/early termination (for a maximum duration of 11 months)
measure: Number of Participants With Clinically Significant Findings in Physical Examination Through the Study
timeFrame: From baseline up to end of study/early termination (for a maximum duration of 11 months)
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA)
timeFrame: From Month 3 up to end of study/early termination (up to Month 11)
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Ocean Sleep Medicine
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Long Beach
country: United States
facility: MemorialCare Sleep Disorders Center at Long Beach Memorial Medical Center
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
state: California
city: Wilmington
country: United States
facility: Nemours Children's Hospital, Delaware
state: Delaware
city: Houston
country: United States
facility: Texas Childrens Hospital/Baylor College of Medicine
state: Texas
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: Leuven
country: Belgium
facility: UZ Leuven - Center of Human Genetics
state: Vlaams - Gewest
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Kobenhavn
country: Denmark
facility: Bispebjerg Hospital
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS Università Cattolica del Sacro Cuore
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra - Hospital Pediátrico
city: Vitoria - Gasteiz
country: Spain
facility: Hospital Vithas San Jose
state: Alava
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: