Back to resultsSafety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAR442501 in Pediatric Participants With Achondroplasia (upreACH-2)
Primary Purpose
Osteochondrodysplasia
Status
Recruiting
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
SAR442501
Sponsored by
About this trial
This is an interventional treatment trial for Osteochondrodysplasia
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, 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.
Sites / Locations
- Investigational Site Number: 0360001Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Arm Description
Outcomes
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
Secondary Outcome Measures
Change in annualized growth velocity (AGV) Zscore
Change in AGV (cm/year)
Change in height Z score
Change in upper-to-lower body segment ratio
Change in upper to lower extremity ratio
Change in sitting to standing height ratio (crown-to-rump length to total length for infants)
Change in arm span to height ratio
Change in upper arm to forearm length ratio
Change in upper leg to lower leg ratio
Change in head circumference to height ratio
Change in brainstem parameter
Change in surface area of the bony foramen magnum (cm2) as measured by head and neck Magnetic Resonance Imaging (MRI).
Change in skull parameter
Change in dimensions of skull base parameters, and degree of synchondroses fusion as measured by head and neck MRI.
Change in spine morphometric parameter
Change in grading of cord compression and cord constriction as assessed by head and neck MRI.
Change in volumetric parameter
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
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
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
Pediatric Pain Questionnaire (PPQ) score value between 0-4. The lower the better.
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.
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.
Assessment of pharmacokinetic (PK) parameter: plasma concentration of SAR442501
Assessment of PK parameter: maximum plasma concentration observed (Cmax)
Assessment of PK parameter: time to reach Cmax (Tmax)
Assessment of PK parameter: Area under the plasma concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t)
Assessment of PK parameter: concentration observed before treatment administration during repeated dosing (Ctrough)
Assessment of pharmacodynamics (PD) parameter: change in collagen X biomarker (CXM) levels
Assessment of PD parameter: change in osteocalcin levels
Assessment of PD parameter: change in bone-specific alkaline phosphatase
Assessment of PD parameter: change in procollagen type 1 N-terminal propeptide (P1NP) levels
Assessment of PD parameter: change in collagen-type 1 C-Telopeptide (CTX) levels
Number of participants with treatment-emergent anti-drug antibodies (ADA)
Changes in neurological examination
Percentage of participants with changes (i.e. abnormal to normal or normal to abnormal) in neurological examination findings
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT06067425
Brief Title
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAR442501 in Pediatric Participants With Achondroplasia
Acronym
upreACH-2
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 10, 2023 (Actual)
Primary Completion Date
December 2, 2027 (Anticipated)
Study Completion Date
December 2, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteochondrodysplasia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Title
Cohort 2
Arm Type
Experimental
Arm Title
Cohort 3
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
SAR442501
Intervention Description
Solution for injection; Subcutaneous injection
Primary Outcome Measure Information:
Title
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 Outcome Measure Information:
Title
Change in annualized growth velocity (AGV) Zscore
Time Frame
Baseline to Week 26 and Week 52
Title
Change in AGV (cm/year)
Time Frame
Baseline to Week 26 and Week 52
Title
Change in height Z score
Time Frame
Baseline to Week 26 and Week 52
Title
Change in upper-to-lower body segment ratio
Time Frame
Baseline to Week 26 and Week 52
Title
Change in upper to lower extremity ratio
Time Frame
Baseline to Week 26 and Week 52
Title
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
Title
Change in arm span to height ratio
Time Frame
Baseline to Week 26 and Week 52
Title
Change in upper arm to forearm length ratio
Time Frame
Baseline to Week 26 and Week 52
Title
Change in upper leg to lower leg ratio
Time Frame
Baseline to Week 26 and Week 52
Title
Change in head circumference to height ratio
Time Frame
Baseline to Week 26 and Week 52
Title
Change in brainstem parameter
Description
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
Title
Change in skull parameter
Description
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
Title
Change in spine morphometric parameter
Description
Change in grading of cord compression and cord constriction as assessed by head and neck MRI.
Time Frame
Baseline to Week 52
Title
Change in volumetric parameter
Description
Change in brainstem and spinal cord volume as measured by head and neck MRI.
Time Frame
Baseline to Week 52
Title
Change in overall health-related quality of life score in the PedsQL Inventory Generic Core Scale
Description
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
Title
Change in fatigue score in the PedsQL Multidimensional Fatigue Scale
Description
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
Title
Change in present pain and worst pain rating (PPQ) score
Description
Pediatric Pain Questionnaire (PPQ) score value between 0-4. The lower the better.
Time Frame
Baseline to Week 26 and Week 52
Title
Change in mobility and symptom rating (STEMS) score
Description
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
Title
Change in developmental score in the Achondroplasia Developmental Recording Form
Description
Achondroplasia Developmental Recording Form to record the age at which participants achieve developmental milestones. The earlier the better.
Time Frame
Baseline to Week 52
Title
Assessment of pharmacokinetic (PK) parameter: plasma concentration of SAR442501
Time Frame
Baseline to Week 26 and 52
Title
Assessment of PK parameter: maximum plasma concentration observed (Cmax)
Time Frame
Baseline to Week 26 and 52
Title
Assessment of PK parameter: time to reach Cmax (Tmax)
Time Frame
Baseline to Week 26 and 52
Title
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
Title
Assessment of PK parameter: concentration observed before treatment administration during repeated dosing (Ctrough)
Time Frame
Baseline to Week 26 and 52
Title
Assessment of pharmacodynamics (PD) parameter: change in collagen X biomarker (CXM) levels
Time Frame
Baseline to Week 26 and Week 52
Title
Assessment of PD parameter: change in osteocalcin levels
Time Frame
Baseline to Week 26 and Week 52
Title
Assessment of PD parameter: change in bone-specific alkaline phosphatase
Time Frame
Baseline to Week 26 and Week 52
Title
Assessment of PD parameter: change in procollagen type 1 N-terminal propeptide (P1NP) levels
Time Frame
Baseline to Week 26 and Week 52
Title
Assessment of PD parameter: change in collagen-type 1 C-Telopeptide (CTX) levels
Time Frame
Baseline to Week 26 and Week 52
Title
Number of participants with treatment-emergent anti-drug antibodies (ADA)
Time Frame
Baseline to Week 26 and Week 52
Title
Changes in neurological examination
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Days
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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, 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Transparency email recommended (Toll free for US & Canada)
Phone
800-633-1610
Ext
option 6
Email
Contact-US@sanofi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number: 0360001
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Learn more about this trial
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAR442501 in Pediatric Participants With Achondroplasia
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