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

Primary Purpose

Osteogenesis Imperfecta

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

SAR439459

Placebo

About this trial

This is an interventional treatment trial for Osteogenesis Imperfecta

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

UCLA Health_Site Number: 8400006Recruiting
Yale University - Site Number:8400007Recruiting
Indiana University School of Medicine_Site Number: 8400002Recruiting
Kennedy Krieger Institute_Site number 8400004Recruiting
Baylor College of Medicine - Site Number:8400003Recruiting
Westmead Hospital_Site Number :0360003Recruiting
Department of Medicine/ School of Clinical Sciences at Monash Health Monash University_246 Clayton Road_Site Number :0360002Recruiting
Bone Research and Education Centre_Site Number :1240003Recruiting
Toronto general Hospital_Site Number :1240002Recruiting
Hopital Edouard Herriot _Site Number :2500002Recruiting
Hopital Lariboisiere_Site Number :2500001Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

SAR439459

Placebo

Arm Description

Participants will receive a single dose of SAR439459

Participants will receive a single dose of placebo

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

Titer of anti-SAR439459 antibodies (if detected)

Percent change from baseline in bone mineral density (BMD)

Full Information

NCT ID

NCT05231668

First Posted

January 31, 2022

Last Updated

August 1, 2023

Sponsor

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT05231668

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 25, 2022 (Actual)

Primary Completion Date

December 13, 2024 (Anticipated)

Study Completion Date

December 13, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Osteogenesis Imperfecta

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

SAR439459

Arm Type

Experimental

Arm Description

Participants will receive a single dose of SAR439459

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will receive a single dose of placebo

Intervention Type

Drug

Intervention Name(s)

SAR439459

Intervention Description

Powder for solution for infusion; IV infusion

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Solution for infusion; IV infusion

Primary Outcome Measure Information:

Title

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

Time Frame

From baseline to Week 24

Secondary Outcome Measure Information:

Title

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

Time Frame

From baseline to Week 24

Title

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

Time Frame

From baseline to Week 24

Title

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

Time Frame

From baseline to Week 24

Title

Titer of anti-SAR439459 antibodies (if detected)

Time Frame

From baseline to Week 24

Title

Percent change from baseline in bone mineral density (BMD)

Time Frame

From baseline to Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Trial Transparency email recommended (Toll free for US & Canada)

Phone

800-633-1610

Ext

option 6

Contact-US@sanofi.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Sciences & Operations

Organizational Affiliation

Sanofi

Official's Role

Study Director

Facility Information:

Facility Name

UCLA Health_Site Number: 8400006

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Safia Khan

Phone

310-794-3467

sfkhan@mednet.ucla.edu

First Name & Middle Initial & Last Name & Degree

Hannah Ebbers

Phone

310-267-4331

hebbers@mednet.ucla.edu

First Name & Middle Initial & Last Name & Degree

Deborah Krakow, Dr

Facility Name

Yale University - Site Number:8400007

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06510

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jacqueline Prinz

Phone

203-785-5977

jacqueline.prinz@yale.edu

First Name & Middle Initial & Last Name & Degree

Clemens Bergwitz, Dr.

Facility Name

Indiana University School of Medicine_Site Number: 8400002

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marian Hart

Phone

317-948-8346

marihart@iu.edu

First Name & Middle Initial & Last Name & Degree

Erik Imel, Doctor

Facility Name

Kennedy Krieger Institute_Site number 8400004

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21205

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Clinical Trials Unit

Phone

443-923-3850

researchtrials@kennedykrieger.org

First Name & Middle Initial & Last Name & Degree

Mahim Jain, Dr

Facility Name

Baylor College of Medicine - Site Number:8400003

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dianne Nguyen

Phone

713-798-6694

diannen@bcm.edu

First Name & Middle Initial & Last Name & Degree

Sandesh Nagamani, Dr.

Facility Name

Westmead Hospital_Site Number :0360003

City

Westmead

State/Province

New South Wales

ZIP/Postal Code

2145

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yang Song

Phone

8890 3791

yang.song@health.nsw.gov.au

First Name & Middle Initial & Last Name & Degree

Christian Girgis, Dr

Facility Name

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

City

Clayton

State/Province

Victoria

ZIP/Postal Code

3168

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Cat Shore-Lorenti

Phone

+61 (0)3 8572 2582

cat.shore-lorenti@monash.edu

First Name & Middle Initial & Last Name & Degree

Peter Ebeling, Prof

Facility Name

Bone Research and Education Centre_Site Number :1240003

City

Oakville

State/Province

Ontario

ZIP/Postal Code

L6M 1M1

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shehryar Mehmood

Phone

905-844-5677

shehryar@boneresearch.ca

First Name & Middle Initial & Last Name & Degree

Aliya Khan, Dr

Facility Name

Toronto general Hospital_Site Number :1240002

City

Toronto

ZIP/Postal Code

M5G 2C4

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Irene Ho

irene.ho@uhn.ca

First Name & Middle Initial & Last Name & Degree

Angela Cheung, Dr

Facility Name

Hopital Edouard Herriot _Site Number :2500002

City

Lyon

ZIP/Postal Code

69003

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Catherine Planckaert

Phone

33 4 72 11 74 40

c.planckaert@pmo-lyon.fr

First Name & Middle Initial & Last Name & Degree

Roland Chapurlat, Prof

Facility Name

Hopital Lariboisiere_Site Number :2500001

City

Paris

ZIP/Postal Code

75010

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sylvie Fernandez

Phone

33 6 60 93 17 75

sylvie.fernandez-ext@aphp.fr

First Name & Middle Initial & Last Name & Degree

Martine Cohen Solal, Prof

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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

Learn more about this trial

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

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