Single Ascending Dose Study of SAR439459 in Adults With Osteogenesis Imperfecta (OI)

NCT ID: NCT05231668

Last Updated: 2025-09-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-25

Study Completion Date

2024-11-12

Brief Summary

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SAR439459 is a human anti-Transforming growth factor β (TGFβ) monoclonal antibody. This phase 1 clinical study investigates the safety, tolerability, and activity of a single dose of SAR439459 in adult participants with OI.

Participants will receive a single IV dose of SAR439459 with safety, pharmacokinetic (PK), and pharmacodynamic (PD) assessments over 24 weeks.

There will be up to 3 dose cohorts. In addition to safety, tolerability, and PK assessments, bone mineral density (BMD) will be evaluated by dual-energy Xray absorptimetry (DXA) scan and a series of blood biomarkers will be monitored to document pharmacodynamic effects of the single dose of SAR439459.

Detailed Description

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The duration of the study for all participants will be approximately 29 weeks:

* Up to 5 weeks from initiation of screening to dose administration
* Treatment on Day 1
* Follow-up and observation of safety and PD for 24 weeks
* Final study visit at Week 24

Conditions

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Osteogenesis Imperfecta

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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SAR439459

Participants will receive a single dose of SAR439459

Group Type EXPERIMENTAL

SAR439459

Intervention Type DRUG

Powder for solution for infusion; IV infusion

Placebo

Participants will receive a single dose of placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Solution for infusion; IV infusion

Interventions

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SAR439459

Powder for solution for infusion; IV infusion

Intervention Type DRUG

Placebo

Solution for infusion; IV infusion

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Participants who are clinically categorized as Type I or IV osteogenesis imperfecta with a previously documented pathogenic genetic variant in human collagen type 1 alpha 1 gene (COL1A1) or human collagen type 1 alpha 2 gene (COL1A2).
* Participants who have experienced at least 1 bone fracture in the past 10 years OR 2 or more (≥2) fractures since the age of 18.
* Body weight ≥30.0 kg.
* Contraception for sexually active male participants or female patient; not pregnant or breastfeeding; no sperm donating for male participant.
* Signed written informed assent/consent.

Exclusion Criteria

* Previously installed rods or metal hardware that would prevent bone mineral density evaluation of the lumbar spine (note: only two of the L1-L4 vertebrae are necessary for evaluation).
* History of moderate (25-40°) to severe (\>40°) scoliosis assessed as Cobb angle (unless scoliosis does not impact assessment of bone mineral density in the lumbar vertebrae in the opinion of the investigator).
* Postmenopausal women who:

* Are within 5 years of the onset of menopause (for example less than 5 years from their last menstruation or post-hysterectomy), however if the person has been on hormone replacement therapy for more than 1 year prior to enrollment, then they are eligible regardless of time from onset of menopause. The person must be willing to continue hormone replacement therapy throughout the study duration. OR
* Were previously on hormone replacement therapy but have stopped within the past 5 years.
* History of treatment with denosumab, anti-sclerostin antibody, parathyroid hormone, bisphosphonates, or any other experimental therapy for OI within 6 months prior to any study baseline assessment.
* Known bleeding disorder.
* History of significant bleeding event that required hospitalization, surgery, or a blood transfusion that was possibly associated with increased bleeding tendency.
* Any major surgery within the last 28 days prior to investigational medicinal product (IMP) administration.
* Elective surgery or invasive procedure anticipated within 6 months after the IMP administration.
* Therapeutic doses of anticoagulants or antiplatelet agents (eg, 1 mg/kg bid of enoxaparin, 300 mg of aspirin daily, and 75 mg of clopidogrel daily or equivalent) within 7 days prior to the IMP administration.
* Any known central nervous system (CNS) or intraocular lesion that has a risk of bleeding.
* Prior history of skin cancers including melanoma, squamous cell carcinoma, or basal cell carcinoma.
* Clinically significant cardiac valvular disorder or symptomatic heart failure.
* Vitamin D (25-hydoxyvitamin D) \<15 ng/dL; rescreening will be allowed after supplementation.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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UCLA Health_Site Number: 8400006

Los Angeles, California, United States

Site Status

Yale University - Site Number:8400007

New Haven, Connecticut, United States

Site Status

Indiana University School of Medicine_Site Number: 8400002

Indianapolis, Indiana, United States

Site Status

Kennedy Krieger Institute_Site number 8400004

Baltimore, Maryland, United States

Site Status

Cincinnati Children's Hospital Medical Center Site Number : 8400010

Cincinnati, Ohio, United States

Site Status

Vanderbilt University Site Number : 8400011

Nashville, Tennessee, United States

Site Status

Baylor College of Medicine - Site Number:8400003

Houston, Texas, United States

Site Status

Westmead Hospital_Site Number :0360003

Westmead, New South Wales, Australia

Site Status

Department of Medicine/ School of Clinical Sciences at Monash Health Monash University_246 Clayton Road_Site Number :0360002

Clayton, Victoria, Australia

Site Status

Bone Research and Education Centre_Site Number :1240003

Oakville, Ontario, Canada

Site Status

Toronto general Hospital_Site Number :1240002

Toronto, , Canada

Site Status

Hopital Edouard Herriot _Site Number :2500002

Lyon, , France

Site Status

Hopital Lariboisiere_Site Number :2500001

Paris, , France

Site Status

Countries

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United States Australia Canada France

Related Links

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Other Identifiers

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U1111-1269-6569

Identifier Type: REGISTRY

Identifier Source: secondary_id

2024-511369-12-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-004914-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SAD17378

Identifier Type: -

Identifier Source: org_study_id

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