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

About

Brief Summary

SAR439459 is a human anti-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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

Minimum Age

18 Years

Maximum Age

65 Years

Inclusion Criteria:

Participants who are clinically categorized as Type I or IV osteogenesis imperfecta with a previously documented pathogenic genetic variant in COL1A1 or 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.
History of moderate (25-40°) to severe (>40°) scoliosis assessed as Cobb angle.
Postmenopausal women.
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 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.

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