Clinical trial NCT05231668: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Osteogenesis Imperfecta
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-02-09
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events (AEs)/treatment-emergent adverse events (TEAEs)
timeFrame: From baseline to Week 24
Secondary outcomes:
measure: Assessment of PK parameters: area under the curve (AUC)
timeFrame: From baseline to Week 24
measure: Assessment of PK parameters: maximum serum concentration observed (Cmax)
timeFrame: From baseline to Week 24
measure: Assessment of PK parameters: time to reach maximum concentration observed (tmax)
timeFrame: From baseline to Week 24
measure: Titer of anti-SAR439459 antibodies (if detected)
timeFrame: From baseline to Week 24
measure: Percent change from baseline in bone mineral density (BMD)
timeFrame: From baseline to Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Health_Site Number: 8400006
state: California
city: New Haven
country: United States
facility: Yale University - Site Number:8400007
state: Connecticut
city: Indianapolis
country: United States
facility: Indiana University School of Medicine_Site Number: 8400002
state: Indiana
city: Baltimore
country: United States
facility: Kennedy Krieger Institute_Site number 8400004
state: Maryland
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center Site Number : 8400010
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Site Number : 8400011
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine - Site Number:8400003
state: Texas
city: Westmead
country: Australia
facility: Westmead Hospital_Site Number :0360003
state: New South Wales
city: Clayton
country: Australia
facility: Department of Medicine/ School of Clinical Sciences at Monash Health Monash University_246 Clayton Road_Site Number :0360002
state: Victoria
city: Oakville
country: Canada
facility: Bone Research and Education Centre_Site Number :1240003
state: Ontario
city: Toronto
country: Canada
facility: Toronto general Hospital_Site Number :1240002
city: Lyon
country: France
facility: Hopital Edouard Herriot _Site Number :2500002
city: Paris
country: France
facility: Hopital Lariboisiere_Site Number :2500001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: