Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAR442501 in Pediatric Participants With Achondroplasia (upreACH-2)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Osteochondrodysplasia
• Intervention / Treatment: Drug: SAR442501

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 Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Recruiting
      • Investigational Site Number : 0360001
• China
  • Wuhan, China, 430030
    • Recruiting
    • Investigational Site Number : 1560001
• Italy
  • Roma, Italy, 00168
    • Recruiting
    • Investigational Site Number : 3800001
• Korea, Republic of
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03080
      • Recruiting
      • Investigational Site Number : 4100001
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 135-710
      • Recruiting
      • Investigational Site Number : 4100002
• Spain
  • Catalunya [Cataluña]
    • Esplugues de Llobregat, Catalunya [Cataluña], Spain, 08950
      • Recruiting
      • Investigational Site Number : 7240001
  • Pais Vasco
    • Vitoria Gasteiz, Pais Vasco, Spain, 01008
      • Recruiting
      • Investigational Site Number : 7240002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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	Change in surface area of the bony foramen magnum (cm2) as measured by head and neck Magnetic Resonance Imaging (MRI).	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.	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.	Baseline to Week 52
Change in volumetric parameter	Change in brainstem and spinal cord volume as measured by head and neck MRI.	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	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	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.	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.	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.	Baseline to Week 52
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	Percentage of participants with changes (i.e. abnormal to normal or normal to abnormal) in neurological examination findings	Baseline through Week 26 and Week 52

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2023
• Primary Completion (Estimated): December 2, 2027
• Study Completion (Estimated): December 2, 2027

Study Registration Dates

• First Submitted: September 20, 2023
• First Submitted That Met QC Criteria: September 28, 2023
• First Posted (Actual): October 4, 2023

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Dwarfism; Bone Diseases, Developmental; Mucopolysaccharidoses; Achondroplasia; Osteochondrodysplasias; Mucopolysaccharidosis IV
• Other Study ID Numbers: DRI16646; U1111-1280-5374 (Registry Identifier: ICTRP); 2023-503677-37 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No