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

March 13, 2024 updated by: Sanofi

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Trial Transparency email recommended (Toll free for US & Canada)
  • Phone Number: option 6 800-633-1610
  • Email: Contact-US@sanofi.com

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Recruiting
        • Westmead Hospital_Site Number :0360003
        • Principal Investigator:
          • Christian Girgis, Dr
        • Contact:
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Recruiting
        • Department of Medicine/ School of Clinical Sciences at Monash Health Monash University_246 Clayton Road_Site Number :0360002
        • Principal Investigator:
          • Peter Ebeling, Prof
        • Contact:
  • Canada
      • Toronto, Canada, M5G 2C4
        • Recruiting
        • Toronto general Hospital_Site Number :1240002
        • Contact:
        • Principal Investigator:
          • Angela Cheung, Dr
    • Ontario
      • Oakville, Ontario, Canada, L6M 1M1
        • Recruiting
        • Bone Research and Education Centre_Site Number :1240003
        • Contact:
        • Principal Investigator:
          • Aliya Khan, Dr
  • France
      • Lyon, France, 69003
        • Recruiting
        • Hopital Edouard Herriot _Site Number :2500002
        • Contact:
        • Principal Investigator:
          • Roland Chapurlat, Prof
      • Paris, France, 75010
        • Recruiting
        • Hopital Lariboisiere_Site Number :2500001
        • Contact:
        • Principal Investigator:
          • Martine Cohen Solal, Prof
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • UCLA Health_Site Number: 8400006
        • Contact:
        • Principal Investigator:
          • Deborah Krakow, Dr
        • Contact:
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale University - Site Number:8400007
        • Contact:
        • Principal Investigator:
          • Clemens Bergwitz, Dr.
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University School of Medicine_Site Number: 8400002
        • Principal Investigator:
          • Erik Imel, Doctor
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • Kennedy Krieger Institute_Site number 8400004
        • Contact:
        • Principal Investigator:
          • Mahim Jain, Dr
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center Site Number : 8400010
        • Contact:
        • Principal Investigator:
          • Howard Saal, Dr
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Site Number : 8400011
        • Contact:
        • Principal Investigator:
          • Kathryn Dahir, Dr
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine - Site Number:8400003
        • Principal Investigator:
          • Sandesh Nagamani, Dr.
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SAR439459
Participants will receive a single dose of SAR439459
Drug: SAR439459
Powder for solution for infusion; IV infusion
Placebo Comparator: Placebo
Participants will receive a single dose of placebo
Drug: Placebo
Solution for infusion; IV infusion

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Investigators

  • Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 25, 2022

Primary Completion (Estimated)

June 30, 2025

Study Completion (Estimated)

June 30, 2025

Study Registration Dates

First Submitted

January 31, 2022

First Submitted That Met QC Criteria

January 31, 2022

First Posted (Actual)

February 9, 2022

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 13, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAD17378
  • U1111-1269-6569 (Registry Identifier: ICTRP)
  • 2021-004914-21 (EudraCT Number)
  • 2024-511369-12-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Osteogenesis Imperfecta

Clinical Trials on SAR439459

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Egypt

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe