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

Overview

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.

Full Title of Study: “A Phase 1b, Single Ascending Dose, Randomized, Double-blind Study to Evaluate the Safety, Tolerability, and Activity of SAR439459 in Adults With Osteogenesis Imperfecta”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: June 30, 2025

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

Interventions

  • Drug: SAR439459
    • Powder for solution for infusion; IV infusion
  • Drug: Placebo
    • Solution for infusion; IV infusion

Arms, Groups and Cohorts

  • Experimental: SAR439459
    • Participants will receive a single dose of SAR439459
  • Placebo Comparator: Placebo
    • Participants will receive a single dose of placebo

Clinical Trial Outcome Measures

Primary Measures

  • Number of participants with adverse events (AEs)/treatment-emergent adverse events (TEAEs)
    • Time Frame: From baseline to Week 24

Secondary Measures

  • Assessment of PK parameters: area under the curve (AUC)
    • Time Frame: From baseline to Week 24
  • Assessment of PK parameters: maximum serum concentration observed (Cmax)
    • Time Frame: From baseline to Week 24
  • Assessment of PK parameters: time to reach maximum concentration observed (tmax)
    • Time Frame: From baseline to Week 24
  • Titer of anti-SAR439459 antibodies (if detected)
    • Time Frame: From baseline to Week 24
  • Percent change from baseline in bone mineral density (BMD)
    • Time Frame: From baseline to Week 24

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sanofi
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Clinical Sciences & Operations, Study Director, Sanofi
  • Overall Contact(s)
    • Trial Transparency email recommended (Toll free for US & Canada), 800-633-1610, Contact-US@sanofi.com

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