single ascending dose study of sar439459 in adults with osteogenesis imperfecta (oi)

Conditions: Osteogenesis Imperfecta

Summary: 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.

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

Eligibility criteria:
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.