Clinical trial NCT06067425: Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAR442501 in Pediatric Participants With Achondroplasia
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Osteochondrodysplasia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-10-04
Enrollment: 16
Sex: ALL
Minimum age (years): 0
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of participants with adverse events (AE), serious adverse events (SAE), and adverse events of special interest (AESI) during the treatment-emergent period
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: Change in annualized growth velocity (AGV) Zscore
timeFrame: Baseline to Week 26 and Week 52
measure: Change in AGV (cm/year)
timeFrame: Baseline to Week 26 and Week 52
measure: Change in height Z score
timeFrame: Baseline to Week 26 and Week 52
measure: Change in upper-to-lower body segment ratio
timeFrame: Baseline to Week 26 and Week 52
measure: Change in upper to lower extremity ratio
timeFrame: Baseline to Week 26 and Week 52
measure: Change in sitting to standing height ratio (crown-to-rump length to total length for infants)
timeFrame: Baseline to Week 26 and Week 52
measure: Change in arm span to height ratio
timeFrame: Baseline to Week 26 and Week 52
measure: Change in upper arm to forearm length ratio
timeFrame: Baseline to Week 26 and Week 52
measure: Change in upper leg to lower leg ratio
timeFrame: Baseline to Week 26 and Week 52
measure: Change in head circumference to height ratio
timeFrame: Baseline to Week 26 and Week 52
measure: Change in brainstem parameter
timeFrame: Baseline to Week 52
measure: Change in skull parameter
timeFrame: Baseline to Week 52
measure: Change in spine morphometric parameter
timeFrame: Baseline to Week 52
measure: Change in volumetric parameter
timeFrame: Baseline to Week 52
measure: Change in overall health-related quality of life score in the PedsQL Inventory Generic Core Scale
timeFrame: Baseline to Week 26 and Week 52
measure: Change in fatigue score in the PedsQL Multidimensional Fatigue Scale
timeFrame: Baseline to Week 26 and Week 52
measure: Change in present pain and worst pain rating (PPQ) score
timeFrame: Baseline to Week 26 and Week 52
measure: Change in mobility and symptom rating (STEMS) score
timeFrame: Baseline to Week 26 and Week 52
measure: Change in developmental score in the Achondroplasia Developmental Recording Form
timeFrame: Baseline to Week 52
measure: Assessment of pharmacokinetic (PK) parameter: plasma concentration of SAR442501
timeFrame: Baseline to Week 26 and 52
measure: Assessment of PK parameter: maximum plasma concentration observed (Cmax)
timeFrame: Baseline to Week 26 and 52
measure: Assessment of PK parameter: time to reach Cmax (Tmax)
timeFrame: Baseline to Week 26 and 52
measure: Assessment of PK parameter: Area under the plasma concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t)
timeFrame: Baseline to Week 26 and 52
measure: Assessment of PK parameter: concentration observed before treatment administration during repeated dosing (Ctrough)
timeFrame: Baseline to Week 26 and 52
measure: Assessment of pharmacodynamics (PD) parameter: change in collagen X biomarker (CXM) levels
timeFrame: Baseline to Week 26 and Week 52
measure: Assessment of PD parameter: change in osteocalcin levels
timeFrame: Baseline to Week 26 and Week 52
measure: Assessment of PD parameter: change in bone-specific alkaline phosphatase
timeFrame: Baseline to Week 26 and Week 52
measure: Assessment of PD parameter: change in procollagen type 1 N-terminal propeptide (P1NP) levels
timeFrame: Baseline to Week 26 and Week 52
measure: Assessment of PD parameter: change in collagen-type 1 C-Telopeptide (CTX) levels
timeFrame: Baseline to Week 26 and Week 52
measure: Number of participants with treatment-emergent anti-drug antibodies (ADA)
timeFrame: Baseline to Week 26 and Week 52
measure: Changes in neurological examination
timeFrame: Baseline through Week 26 and Week 52
Other outcomes:
Locations:
city: Parkville
country: Australia
facility: Investigational Site Number : 0360001
state: Victoria
city: Shanghai
country: China
facility: Investigational Site Number : 1560002
city: Wuhan
country: China
facility: Investigational Site Number : 1560001
city: Milan
country: Italy
facility: Investigational Site Number : 3800002
state: Lombardia
city: Rome
country: Italy
facility: Investigational Site Number : 3800001
state: Roma
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Esplugues de Llobregat
country: Spain
facility: Investigational Site Number : 7240001
state: Catalunya [Cataluña]
city: Vitoria-gasteiz
country: Spain
facility: Investigational Site Number : 7240002
state: Pais Vasco
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: