A Phase 2, Open-label, Multi-center, 2-stage Sequential Cohort, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Subcutaneous SAR442501 in Pediatric Participants With Achondroplasia

Sanofi9 sites in 5 countries16 target enrollmentOctober 10, 2023

ConditionsOsteochondrodysplasia

InterventionsSAR442501

DrugsSAR442501

Overview

Phase: Phase 2
Intervention: SAR442501
Conditions: Osteochondrodysplasia
Sponsor: Sanofi
Enrollment: 16
Locations: 9
Primary Endpoint: Number of participants with adverse events (AE), serious adverse events (SAE), and adverse events of special interest (AESI) during the treatment-emergent period
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 2, open-label, multicenter, study to evaluate safety, tolerability and efficacy of SAR442501 in children from birth up to 12 years of age with Achondroplasia.

Detailed Description

Up to approximately 275 weeks: 3 weeks Screening + 52 weeks primary treatment period + up to approximately 216 weeks extended treatment period+ 4 weeks follow-up.

Registry

clinicaltrials.gov

Start Date

October 10, 2023

End Date

February 12, 2025

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Sanofi

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participants must have ACH with a confirmed mutation in the FGFR3 gene
•Participants and/or parent(s) or legal representative(s) must be willing and able to perform all the study procedures to the best of their physical ability.
•Parent(s) or legal representative(s) capable of giving signed informed consent and participants capable of giving assent when applicable.

Exclusion Criteria

•Have hypochondroplasia (or the N540K mutation) or short stature condition other than ACH (eg, trisomy 21, pseudochondroplasia)
•Participants have received any dose of medications or investigational product, including human growth hormone, IGF-1, intended to affect participants' stature or body proportions between the completion of OBS16647 and enrollment (Week 0/Day 1/Visit 2).
•Have a history of growth plate closure.
•Long bone fracture within 3 months of enrollment (Week 0/Day 1/Visit 2)
•Current evidence of corneal or retinal disorder/keratopathy.
•Participants have had a previous surgical intervention involving the foramen magnum (Stage 2 only).
•Hyperphosphatemia.
•The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Arms & Interventions

Cohort 2

Intervention: SAR442501

Cohort 1

Intervention: SAR442501

Cohort 3

Intervention: SAR442501

Outcomes

Primary Outcomes

Number of participants with adverse events (AE), serious adverse events (SAE), and adverse events of special interest (AESI) during the treatment-emergent period

Time Frame: Baseline to Week 52

Secondary Outcomes

Change in upper-to-lower body segment ratio(Baseline to Week 26 and Week 52)
Change in sitting to standing height ratio (crown-to-rump length to total length for infants)(Baseline to Week 26 and Week 52)
Change in arm span to height ratio(Baseline to Week 26 and Week 52)
Change in upper arm to forearm length ratio(Baseline to Week 26 and Week 52)
Change in annualized growth velocity (AGV) Zscore(Baseline to Week 26 and Week 52)
Change in AGV (cm/year)(Baseline to Week 26 and Week 52)
Change in height Z score(Baseline to Week 26 and Week 52)
Change in head circumference to height ratio(Baseline to Week 26 and Week 52)
Change in volumetric parameter(Baseline to Week 52)
Change in developmental score in the Achondroplasia Developmental Recording Form(Baseline to Week 52)
Assessment of PK parameter: maximum plasma concentration observed (Cmax)(Baseline to Week 26 and 52)
Assessment of PD parameter: change in osteocalcin levels(Baseline to Week 26 and Week 52)
Change in upper to lower extremity ratio(Baseline to Week 26 and Week 52)
Change in brainstem parameter(Baseline to Week 52)
Change in upper leg to lower leg ratio(Baseline to Week 26 and Week 52)
Change in skull parameter(Baseline to Week 52)
Change in present pain and worst pain rating (PPQ) score(Baseline to Week 26 and Week 52)
Assessment of PK parameter: concentration observed before treatment administration during repeated dosing (Ctrough)(Baseline to Week 26 and 52)
Assessment of pharmacodynamics (PD) parameter: change in collagen X biomarker (CXM) levels(Baseline to Week 26 and Week 52)
Assessment of PD parameter: change in collagen-type 1 C-Telopeptide (CTX) levels(Baseline to Week 26 and Week 52)
Change in mobility and symptom rating (STEMS) score(Baseline to Week 26 and Week 52)
Assessment of PD parameter: change in procollagen type 1 N-terminal propeptide (P1NP) levels(Baseline to Week 26 and Week 52)
Change in spine morphometric parameter(Baseline to Week 52)
Change in fatigue score in the PedsQL Multidimensional Fatigue Scale(Baseline to Week 26 and Week 52)
Assessment of PK parameter: Area under the plasma concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t)(Baseline to Week 26 and 52)
Number of participants with treatment-emergent anti-drug antibodies (ADA)(Baseline to Week 26 and Week 52)
Change in overall health-related quality of life score in the PedsQL Inventory Generic Core Scale(Baseline to Week 26 and Week 52)
Assessment of pharmacokinetic (PK) parameter: plasma concentration of SAR442501(Baseline to Week 26 and 52)
Assessment of PK parameter: time to reach Cmax (Tmax)(Baseline to Week 26 and 52)
Assessment of PD parameter: change in bone-specific alkaline phosphatase(Baseline to Week 26 and Week 52)
Changes in neurological examination(Baseline through Week 26 and Week 52)