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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06067425




Registration number
NCT06067425
Ethics application status
Date submitted
20/09/2023
Date registered
4/10/2023
Date last updated
20/11/2024

Titles & IDs
Public title
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAR442501 in Pediatric Participants With Achondroplasia
Scientific 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
Secondary ID [1] 0 0
U1111-1280-5374
Secondary ID [2] 0 0
DRI16646
Universal Trial Number (UTN)
Trial acronym
upreACH-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteochondrodysplasia 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SAR442501

Experimental: Cohort 1 -

Experimental: Cohort 2 -

Experimental: Cohort 3 -


Treatment: Drugs: SAR442501
Solution for injection; Subcutaneous injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events (AE), serious adverse events (SAE), and adverse events of special interest (AESI) during the treatment-emergent period
Timepoint [1] 0 0
Baseline to Week 52
Secondary outcome [1] 0 0
Change in annualized growth velocity (AGV) Zscore
Timepoint [1] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [2] 0 0
Change in AGV (cm/year)
Timepoint [2] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [3] 0 0
Change in height Z score
Timepoint [3] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [4] 0 0
Change in upper-to-lower body segment ratio
Timepoint [4] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [5] 0 0
Change in upper to lower extremity ratio
Timepoint [5] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [6] 0 0
Change in sitting to standing height ratio (crown-to-rump length to total length for infants)
Timepoint [6] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [7] 0 0
Change in arm span to height ratio
Timepoint [7] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [8] 0 0
Change in upper arm to forearm length ratio
Timepoint [8] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [9] 0 0
Change in upper leg to lower leg ratio
Timepoint [9] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [10] 0 0
Change in head circumference to height ratio
Timepoint [10] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [11] 0 0
Change in brainstem parameter
Timepoint [11] 0 0
Baseline to Week 52
Secondary outcome [12] 0 0
Change in skull parameter
Timepoint [12] 0 0
Baseline to Week 52
Secondary outcome [13] 0 0
Change in spine morphometric parameter
Timepoint [13] 0 0
Baseline to Week 52
Secondary outcome [14] 0 0
Change in volumetric parameter
Timepoint [14] 0 0
Baseline to Week 52
Secondary outcome [15] 0 0
Change in overall health-related quality of life score in the PedsQL Inventory Generic Core Scale
Timepoint [15] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [16] 0 0
Change in fatigue score in the PedsQL Multidimensional Fatigue Scale
Timepoint [16] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [17] 0 0
Change in present pain and worst pain rating (PPQ) score
Timepoint [17] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [18] 0 0
Change in mobility and symptom rating (STEMS) score
Timepoint [18] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [19] 0 0
Change in developmental score in the Achondroplasia Developmental Recording Form
Timepoint [19] 0 0
Baseline to Week 52
Secondary outcome [20] 0 0
Assessment of pharmacokinetic (PK) parameter: plasma concentration of SAR442501
Timepoint [20] 0 0
Baseline to Week 26 and 52
Secondary outcome [21] 0 0
Assessment of PK parameter: maximum plasma concentration observed (Cmax)
Timepoint [21] 0 0
Baseline to Week 26 and 52
Secondary outcome [22] 0 0
Assessment of PK parameter: time to reach Cmax (Tmax)
Timepoint [22] 0 0
Baseline to Week 26 and 52
Secondary outcome [23] 0 0
Assessment of PK parameter: Area under the plasma concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t)
Timepoint [23] 0 0
Baseline to Week 26 and 52
Secondary outcome [24] 0 0
Assessment of PK parameter: concentration observed before treatment administration during repeated dosing (Ctrough)
Timepoint [24] 0 0
Baseline to Week 26 and 52
Secondary outcome [25] 0 0
Assessment of pharmacodynamics (PD) parameter: change in collagen X biomarker (CXM) levels
Timepoint [25] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [26] 0 0
Assessment of PD parameter: change in osteocalcin levels
Timepoint [26] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [27] 0 0
Assessment of PD parameter: change in bone-specific alkaline phosphatase
Timepoint [27] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [28] 0 0
Assessment of PD parameter: change in procollagen type 1 N-terminal propeptide (P1NP) levels
Timepoint [28] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [29] 0 0
Assessment of PD parameter: change in collagen-type 1 C-Telopeptide (CTX) levels
Timepoint [29] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [30] 0 0
Number of participants with treatment-emergent anti-drug antibodies (ADA)
Timepoint [30] 0 0
Baseline to Week 26 and Week 52
Secondary outcome [31] 0 0
Changes in neurological examination
Timepoint [31] 0 0
Baseline through Week 26 and Week 52

Eligibility
Key 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.
Minimum age
0 Days
Maximum age
12 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/12/2027
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Investigational Site Number : 0360001 - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
China
State/province [1] 0 0
Shanghai
Country [2] 0 0
China
State/province [2] 0 0
Wuhan
Country [3] 0 0
Italy
State/province [3] 0 0
Lombardia
Country [4] 0 0
Italy
State/province [4] 0 0
Roma
Country [5] 0 0
Korea, Republic of
State/province [5] 0 0
Seoul-teukbyeolsi
Country [6] 0 0
Spain
State/province [6] 0 0
Catalunya [Cataluña]
Country [7] 0 0
Spain
State/province [7] 0 0
Pais Vasco

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT06067425
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06067425