upreACH-2: Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAR442501 in Pediatric Participants With Achondroplasia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1
|
Drug: SAR442501
Solution for injection; Subcutaneous injection
|
| Experimental: Cohort 2
|
Drug: SAR442501
Solution for injection; Subcutaneous injection
|
| Experimental: Cohort 3
|
Drug: SAR442501
Solution for injection; Subcutaneous injection
|
Outcome Measures
Primary Outcome Measures
- Number of participants with adverse events (AE), serious adverse events (SAE), and adverse events of special interest (AESI) during the treatment-emergent period [Baseline to Week 52]
Secondary Outcome Measures
- 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 upper-to-lower body segment ratio [Baseline to Week 26 and Week 52]
- Change in upper to lower extremity 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 upper leg to lower leg ratio [Baseline to Week 26 and Week 52]
- Change in head circumference to height ratio [Baseline to Week 26 and Week 52]
- Change in brainstem parameter [Baseline to Week 52]
Change in surface area of the bony foramen magnum (cm2) as measured by head and neck Magnetic Resonance Imaging (MRI).
- Change in skull parameter [Baseline to Week 52]
Change in dimensions of skull base parameters, and degree of synchondroses fusion as measured by head and neck MRI.
- Change in spine morphometric parameter [Baseline to Week 52]
Change in grading of cord compression and cord constriction as assessed by head and neck MRI.
- Change in volumetric parameter [Baseline to Week 52]
Change in brainstem and spinal cord volume as measured by head and neck MRI.
- Change in overall health-related quality of life score in the PedsQL Inventory Generic Core Scale [Baseline to Week 26 and Week 52]
PedsQL Generic Core Scales, global score ranging from 0-100, with higher scores representing better outcomes
- Change in fatigue score in the PedsQL Multidimensional Fatigue Scale [Baseline to Week 26 and Week 52]
PedsQL Multidimensional Fatigue Scale, global score ranging from 0-100, with higher scores representing better outcomes
- Change in present pain and worst pain rating (PPQ) score [Baseline to Week 26 and Week 52]
Pediatric Pain Questionnaire (PPQ) score value between 0-4. The lower the better.
- Change in mobility and symptom rating (STEMS) score [Baseline to Week 26 and Week 52]
Screening Tool for Everyday Mobility and Symptoms (STEMS) score value between 1-5. The lower the better.
- Change in developmental score in the Achondroplasia Developmental Recording Form [Baseline to Week 52]
Achondroplasia Developmental Recording Form to record the age at which participants achieve developmental milestones. The earlier the better.
- Assessment of pharmacokinetic (PK) parameter: plasma concentration of SAR442501 [Baseline to Week 26 and 52]
- Assessment of PK parameter: maximum plasma concentration observed (Cmax) [Baseline to Week 26 and 52]
- Assessment of PK parameter: time to reach Cmax (Tmax) [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) [Baseline to Week 26 and 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 osteocalcin levels [Baseline to Week 26 and Week 52]
- Assessment of PD parameter: change in bone-specific alkaline phosphatase [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]
- Assessment of PD parameter: change in collagen-type 1 C-Telopeptide (CTX) levels [Baseline to Week 26 and Week 52]
- Number of participants with treatment-emergent anti-drug antibodies (ADA) [Baseline to Week 26 and Week 52]
- Changes in neurological examination [Baseline through Week 26 and Week 52]
Percentage of participants with changes (i.e. abnormal to normal or normal to abnormal) in neurological examination findings
Eligibility Criteria
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, intended to affect participants' stature or body proportions within 6 months of 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site Number: 0360001 | Parkville | Victoria | Australia | 3052 |
Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DRI16646
- U1111-1280-5374
- 2023-503677-37