Single Ascending Dose Study of SAR439459 in Adults With Osteogenesis Imperfecta (OI)
- Registration Number
- NCT05231668
- Lead Sponsor
- Sanofi
- 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.
- 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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 16
- 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.
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description SAR439459 SAR439459 Participants will receive a single dose of SAR439459 Placebo Placebo Participants will receive a single dose of placebo
- Primary Outcome Measures
Name Time Method Number of participants with adverse events (AEs)/treatment-emergent adverse events (TEAEs) From baseline to Week 24
- Secondary Outcome Measures
Name Time Method Assessment of PK parameters: maximum serum concentration observed (Cmax) From baseline to Week 24 Assessment of PK parameters: area under the curve (AUC) 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
Trial Locations
- Locations (13)
UCLA Health_Site Number: 8400006
🇺🇸Los Angeles, California, United States
Yale University - Site Number:8400007
🇺🇸New Haven, Connecticut, United States
Indiana University School of Medicine_Site Number: 8400002
🇺🇸Indianapolis, Indiana, United States
Kennedy Krieger Institute_Site number 8400004
🇺🇸Baltimore, Maryland, United States
Cincinnati Children's Hospital Medical Center Site Number : 8400010
🇺🇸Cincinnati, Ohio, United States
Vanderbilt University Site Number : 8400011
🇺🇸Nashville, Tennessee, United States
Baylor College of Medicine - Site Number:8400003
🇺🇸Houston, Texas, United States
Westmead Hospital_Site Number :0360003
🇦🇺Westmead, New South Wales, Australia
Department of Medicine/ School of Clinical Sciences at Monash Health Monash University_246 Clayton Road_Site Number :0360002
🇦🇺Clayton, Victoria, Australia
Bone Research and Education Centre_Site Number :1240003
🇨🇦Oakville, Ontario, Canada
Toronto general Hospital_Site Number :1240002
🇨🇦Toronto, Canada
Hopital Edouard Herriot _Site Number :2500002
🇫🇷Lyon, France
Hopital Lariboisiere_Site Number :2500001
🇫🇷Paris, France