Single Ascending Dose Study of SAR439459 in Adults With Osteogenesis Imperfecta (OI)
Purpose
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.
Condition
- Osteogenesis Imperfecta
Eligibility
- Eligible Ages
- Between 18 Years and 65 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental SAR439459 |
Participants will receive a single dose of SAR439459 |
|
|
Placebo Comparator Placebo |
Participants will receive a single dose of placebo |
|
Recruiting Locations
Vanderbilt University Site Number : 8400011
Nashville, Tennessee 37232
Nashville, Tennessee 37232
More Details
- Status
- Recruiting
- Sponsor
- Sanofi
Study Contact
Trial Transparency email recommended (Toll free for US & Canada)800-633-1610
Contact-US@sanofi.com
Detailed Description
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