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

Osteogenesis Imperfecta Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05231668
• Other study ID #: SAD17378
• Secondary ID: U1111-1269-65692
• Status: Recruiting
• Phase: Phase 1
• Start date: August 25, 2022
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteogenesis Imperfecta

Intervention

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

Locations

Country	Name	City	State
Australia	Department of Medicine/ School of Clinical Sciences at Monash Health Monash University_246 Clayton Road_Site Number :0360002	Clayton	Victoria
Australia	Westmead Hospital_Site Number :0360003	Westmead	New South Wales
Canada	Bone Research and Education Centre_Site Number :1240003	Oakville	Ontario
Canada	Toronto general Hospital_Site Number :1240002	Toronto
France	Hopital Edouard Herriot _Site Number :2500002	Lyon
France	Hopital Lariboisiere_Site Number :2500001	Paris
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	Baylor College of Medicine - Site Number:8400003	Houston	Texas
United States	Indiana University School of Medicine_Site Number: 8400002	Indianapolis	Indiana
United States	UCLA Health_Site Number: 8400006	Los Angeles	California
United States	Vanderbilt University Site Number : 8400011	Nashville	Tennessee
United States	Yale University - Site Number:8400007	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events (AEs)/treatment-emergent adverse events (TEAEs)		From baseline to Week 24
Secondary	Assessment of PK parameters: area under the curve (AUC)		From baseline to Week 24
Secondary	Assessment of PK parameters: maximum serum concentration observed (Cmax)		From baseline to Week 24
Secondary	Assessment of PK parameters: time to reach maximum concentration observed (tmax)		From baseline to Week 24
Secondary	Titer of anti-SAR439459 antibodies (if detected)		From baseline to Week 24
Secondary	Percent change from baseline in bone mineral density (BMD)		From baseline to Week 24