Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAR442501 in Pediatric Participants With Achondroplasia

Phase 2TerminatedNCT06067425

Sanofi16 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Osteochondrodysplasia

Interventions

SAR442501DRUG

Solution for injection; Subcutaneous injection

Eligibility

Sex: ALLMin age: 0 DaysMax age: 12 Years

Medical Language ↔ Plain English

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.

Locations (9)

Investigational Site Number : 0360001

Parkville, Victoria, Australia

Investigational Site Number : 1560002

Shanghai, China

Investigational Site Number : 1560001

Wuhan, China

Investigational Site Number : 3800002

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 annualized growth velocity (AGV) Zscore

Time frame: Baseline to Week 26 and Week 52

Change in AGV (cm/year)

Time frame: Baseline to Week 26 and Week 52

Change in height Z score

Time frame: Baseline to Week 26 and Week 52

Change in upper-to-lower body segment ratio

Time frame: Baseline to Week 26 and Week 52

Change in upper to lower extremity ratio

Time frame: Baseline to Week 26 and Week 52

Change in sitting to standing height ratio (crown-to-rump length to total length for infants)

Time frame: Baseline to Week 26 and Week 52

Change in arm span to height ratio

Time frame: Baseline to Week 26 and Week 52

Change in upper arm to forearm length ratio

Time frame: Baseline to Week 26 and Week 52

Change in upper leg to lower leg ratio

Time frame: Baseline to Week 26 and Week 52

Change in head circumference to height ratio

Data from ClinicalTrials.gov

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Milan, Lombardy, Italy

Investigational Site Number : 3800001

Rome, Roma, Italy

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 7240002

Vitoria-Gasteiz, Basque Country, Spain

Investigational Site Number : 7240001

Esplugues de Llobregat, Catalunya [Cataluña], Spain

Time frame: Baseline to Week 26 and Week 52

Change in brainstem parameter

Change in surface area of the bony foramen magnum (cm2) as measured by head and neck Magnetic Resonance Imaging (MRI).

Time frame: Baseline to Week 52

Change in skull parameter

Change in dimensions of skull base parameters, and degree of synchondroses fusion as measured by head and neck MRI.

Time frame: Baseline to Week 52

Change in spine morphometric parameter

Change in grading of cord compression and cord constriction as assessed by head and neck MRI.

Time frame: Baseline to Week 52

Change in volumetric parameter

Change in brainstem and spinal cord volume as measured by head and neck MRI.

Time frame: Baseline to Week 52

Change in overall health-related quality of life score in the PedsQL Inventory Generic Core Scale

PedsQL Generic Core Scales, global score ranging from 0-100, with higher scores representing better outcomes

Time frame: Baseline to Week 26 and Week 52

Change in fatigue score in the PedsQL Multidimensional Fatigue Scale

PedsQL Multidimensional Fatigue Scale, global score ranging from 0-100, with higher scores representing better outcomes

Time frame: Baseline to Week 26 and Week 52

Change in present pain and worst pain rating (PPQ) score

Pediatric Pain Questionnaire (PPQ) score value between 0-4. The lower the better.

Time frame: Baseline to Week 26 and Week 52

Change in mobility and symptom rating (STEMS) score

Screening Tool for Everyday Mobility and Symptoms (STEMS) score value between 1-5. The lower the better.

Time frame: Baseline to Week 26 and Week 52

Change in developmental score in the Achondroplasia Developmental Recording Form

Achondroplasia Developmental Recording Form to record the age at which participants achieve developmental milestones. The earlier the better.

Time frame: Baseline to Week 52

Assessment of pharmacokinetic (PK) parameter: plasma concentration of SAR442501

Time frame: Baseline to Week 26 and 52

Assessment of PK parameter: maximum plasma concentration observed (Cmax)

Time frame: Baseline to Week 26 and 52

Assessment of PK parameter: time to reach Cmax (Tmax)

Time frame: Baseline to Week 26 and 52

Assessment of PK parameter: Area under the plasma concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t)

Time frame: Baseline to Week 26 and 52

Assessment of PK parameter: concentration observed before treatment administration during repeated dosing (Ctrough)

Time frame: Baseline to Week 26 and 52

Assessment of pharmacodynamics (PD) parameter: change in collagen X biomarker (CXM) levels

Time frame: Baseline to Week 26 and Week 52

Assessment of PD parameter: change in osteocalcin levels

Time frame: Baseline to Week 26 and Week 52

Assessment of PD parameter: change in bone-specific alkaline phosphatase

Time frame: Baseline to Week 26 and Week 52

Assessment of PD parameter: change in procollagen type 1 N-terminal propeptide (P1NP) levels

Time frame: Baseline to Week 26 and Week 52

Assessment of PD parameter: change in collagen-type 1 C-Telopeptide (CTX) levels

Time frame: Baseline to Week 26 and Week 52

Number of participants with treatment-emergent anti-drug antibodies (ADA)

Time frame: Baseline to Week 26 and Week 52

Changes in neurological examination

Percentage of participants with changes (i.e. abnormal to normal or normal to abnormal) in neurological examination findings

Time frame: Baseline through Week 26 and Week 52