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

NCT05231668 | Terminated Phase 1 FDA Drug

• 4 other identifiers: SAD17378U1111-1269-65692024-511369-12-002021-004914-21
• Study Type: interventional
• Target: 16
• Locations: 4 countries
• Sites: 13

Brief 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.

Conditions

Osteogenesis Imperfecta

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events (AEs)/treatment-emergent adverse events (TEAEs)

  From baseline to Week 24

Secondary Outcomes (5)

• Assessment of PK parameters: area under the curve (AUC)

  From baseline to Week 24

• Assessment of PK parameters: maximum serum concentration observed (Cmax)

  From baseline to Week 24

• Assessment of PK parameters: time to reach maximum concentration observed (tmax)

  From baseline to Week 24

• Titer of anti-SAR439459 antibodies (if detected)

  From baseline to Week 24

• Percent change from baseline in bone mineral density (BMD)

  From baseline to Week 24

Study Arms (2)

SAR439459

EXPERIMENTAL

Participants will receive a single dose of SAR439459

Drug: SAR439459

Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of placebo

Drug: Placebo

Interventions

SAR439459 DRUG

Powder for solution for infusion; IV infusion

SAR439459

Placebo DRUG

Solution for infusion; IV infusion

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (13)

UCLA Health_Site Number: 8400006

Los Angeles, California, 90095, United States

Location

Yale University - Site Number:8400007

New Haven, Connecticut, 06510, United States

Location

Indiana University School of Medicine_Site Number: 8400002

Indianapolis, Indiana, 46202, United States

Location

Kennedy Krieger Institute_Site number 8400004

Baltimore, Maryland, 21205, United States

Location

Cincinnati Children's Hospital Medical Center Site Number : 8400010

Cincinnati, Ohio, 45229, United States

Location

Vanderbilt University Site Number : 8400011

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine - Site Number:8400003

Houston, Texas, 77030, United States

Location

Westmead Hospital_Site Number :0360003

Westmead, New South Wales, 2145, Australia

Location

Department of Medicine/ School of Clinical Sciences at Monash Health Monash University_246 Clayton Road_Site Number :0360002

Clayton, Victoria, 3168, Australia

Location

Bone Research and Education Centre_Site Number :1240003

Oakville, Ontario, L6M 1M1, Canada

Location

Toronto general Hospital_Site Number :1240002

Toronto, M5G 2C4, Canada

Location

Hopital Edouard Herriot _Site Number :2500002

Lyon, 69003, France

Location

Hopital Lariboisiere_Site Number :2500001

Paris, 75010, France

Location

Related Links

• SAD17378 Plain Language Results Summary

MeSH Terms

Conditions

Osteogenesis Imperfecta

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2022
• First Posted: February 9, 2022
• Study Start: August 25, 2022
• Primary Completion: November 12, 2024
• Study Completion: November 12, 2024
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

CA (2); FR (2); AU (2); US (7)