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

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.