Safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SAR442501 in pediatric participants with Achondroplasia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

24 Oct 2023 → 12 Feb 2025

Decision date (initial)

2023-09-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Sanofi Research & Development

External identifiers

EU CT number

2023-503677-37-00

WHO UTN

U1111-1280-5374

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Pharmacodynamic

To assess the safety and tolerability of SAR442501 administered subcutaneously (SC) in participants with achondroplasia (ACH)

Secondary objectives 12

1. To evaluate changes in growth parameters
2. To evaluate changes in body proportionality
3. To evaluate changes in foramen magnum
4. To evaluate changes in health-related quality of life (QoL) as measured by the pediatric quality of life (PedsQL) Inventory Generic Core Scale
5. To evaluate changes in fatigue as measured by the PedsQL Multidimensional Fatigue Scale
6. To evaluate changes in pain as measured by the PedsQL Pediatric Pain Questionnaire
7. To evaluate changes in mobility as measured by the STEMS
8. To collect developmental milestone data as measured by the Achondroplasia Developmental Recording Form
9. To evaluate the pharmacokinetic profile of SAR442501
10. To characterize changes from baseline in bone/collagen biomarkers
11. To evaluate the immunogenicity of SAR442501
12. To evaluate clinical signs and symptoms of foramen magnum stenosis

Conditions and MedDRA coding

Osteochondrodysplasia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Participants must have ACH with a confirmed mutation in the FGFR3 gene
2. Participants and/or parent(s) or legal representative must be willing and able to perform all the study procedures to the best of their physical ability.
3. Parent(s) or legal representative capable of giving signed informed consent and participants capable of giving assent when applicable.

Exclusion criteria 7

1. Have hypochondroplasia (or the N540K mutation) or short stature condition other than ACH (eg, trisomy 21, pseudochondroplasia)
2. 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).
3. Have a history of growth plate closure.
4. Long bone fracture within 3 months of enrollment (Week 0/Day 1/Visit 2)
5. Current evidence of corneal or retinal disorder/keratopathy.
6. Participants have had a previous surgical intervention involving the foramen magnum (Stage 2 only).
7. Hyperphosphatemia

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of participants with adverse events (AE), serious adverse events (SAE), and adverse events of special interest (AESI) during the treatment-emergent period

Secondary endpoints 31

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 10

Locations

3 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications