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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05231668




Registration number
NCT05231668
Ethics application status
Date submitted
31/01/2022
Date registered
9/02/2022
Date last updated
15/03/2024

Titles & IDs
Public title
Single Ascending Dose Study of SAR439459 in Adults With Osteogenesis Imperfecta (OI)
Scientific 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
Secondary ID [1] 0 0
U1111-1269-6569
Secondary ID [2] 0 0
SAD17378
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteogenesis Imperfecta 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Injuries and Accidents 0 0 0 0
Fractures

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SAR439459
Treatment: Drugs - Placebo

Experimental: SAR439459 - Participants will receive a single dose of SAR439459

Placebo Comparator: Placebo - Participants will receive a single dose of placebo


Treatment: Drugs: SAR439459
Powder for solution for infusion; IV infusion

Treatment: Drugs: Placebo
Solution for infusion; IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events (AEs)/treatment-emergent adverse events (TEAEs)
Timepoint [1] 0 0
From baseline to Week 24
Secondary outcome [1] 0 0
Assessment of PK parameters: area under the curve (AUC)
Timepoint [1] 0 0
From baseline to Week 24
Secondary outcome [2] 0 0
Assessment of PK parameters: maximum serum concentration observed (Cmax)
Timepoint [2] 0 0
From baseline to Week 24
Secondary outcome [3] 0 0
Assessment of PK parameters: time to reach maximum concentration observed (tmax)
Timepoint [3] 0 0
From baseline to Week 24
Secondary outcome [4] 0 0
Titer of anti-SAR439459 antibodies (if detected)
Timepoint [4] 0 0
From baseline to Week 24
Secondary outcome [5] 0 0
Percent change from baseline in bone mineral density (BMD)
Timepoint [5] 0 0
From baseline to Week 24

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/08/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2025
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Westmead Hospital_Site Number :0360003 - Westmead
Recruitment hospital [2] 0 0
Department of Medicine/ School of Clinical Sciences at Monash Health Monash University_246 Clayton Road_Site Number :0360002 - Clayton
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Toronto
Country [10] 0 0
France
State/province [10] 0 0
Lyon
Country [11] 0 0
France
State/province [11] 0 0
Paris

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
SAR439459 is a human anti-Transforming growth factor ß (TGFß) 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05231668
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
Contact-US@sanofi.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05231668