A Randomized, Double-blind, Placebo-controlled Study of the Tolerability, Pharmacokinetics and Pharmacodynamics of Ascending Single and Repeated Subcutaneous Doses of SAR444336 in Healthy Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- SAR444336
- Conditions
- Healthy Volunteer
- Sponsor
- Sanofi
- Enrollment
- 76
- Locations
- 2
- Primary Endpoint
- Part 1: Number of subjects with treatment-emergent adverse events (TEAEs)
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
This phase 1 study will assess the safety and tolerability, and characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of SAR444336 in healthy subjects following single- and repeated-dose administrations as a first step in clinical development prior to administering this new investigational medicinal product (IMP) to patients.
Detailed Description
The anticipated study duration per participant is up to 10 weeks in Part 1. * Screening: 2 to 28 days prior to dosing (Day -28 to Day -2) * Treatment period: Day -1 to Day 29 post dose including * Institutionalization: Day -1 until Day 8 * Ambulant period including repeat PK and PD blood sampling and ambulant visits: Day 9 to Day 29 * Follow-up period: Day 30 to Day 43 The anticipated study duration per participant is up to 17 weeks in Part 2. * Screening: 2 to 28 days prior to dosing (Day -28 to Day -2) * Treatment period: Day -1 to Day 57 (Q2W/3 doses or Q4W/2 doses) or Day -1 to Day 85 (Q4W/3 doses), or Day -1 to Day 50 (Q3W) including * Institutionalization: Day -1 until Day 3 * Ambulant period including repeat PK and PD blood sampling, ambulant visits and 24 hours institutionalization after 2nd and/or 3rd dose: Day 4 to Day 57 (Q2W/3 doses, Q4W/2 doses), Day 4 to Day 85 (Q4W/3 doses) or Day 50 (Q3W) * Follow-up period: Day 58 to Day 71 (Q2W/3 doses or Q4W/2 doses), Day 71 to Day 85 (Q4W/3 doses) or Day 51 to Day 64 (Q3W)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female participants between 18 and 55 years of age inclusive.
- •Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG.
- •Laboratory values within normal range unless the abnormality is considered not clinical relevant by the investigator. The following parameters, however, must be within normal range: platelet count, and CRP. ALT, AST, total bilirubin (unless the participant has documented or suspected Gilbert syndrome) should be \<1.25 ULN and serum creatinine should be \< ULN.
- •Eosinophils \<500 cells/µL
- •Normal vital signs after 10 minutes resting in supine position
- •Standard 12-lead ECG parameters after 10 minutes resting in supine position in the normal ranges and normal ECG tracing unless the Investigator considers an ECG tracing abnormality to be not clinically relevant.
- •Body weight between 50 - 110 kg (inclusive) and body mass index (BMI) between 18 - 30 kg/m2 (inclusive) at screening.
- •Only for part 2: Fitzpatrick skin type I - III
Exclusion Criteria
- •Any disease associated with immune system dysfunction.
- •Known polyethylene glycol allergy
- •Only for Part 2: Known seafood allergy
- •Any current active viral, bacterial or fungal infection or any medically relevant infection having occurred within 3 weeks before inclusion.
- •Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, autoimmune, systemic, ocular, or infectious disease, or signs of acute illness that would pose an unacceptable risk to the subject in the opinion of the investigator.
- •Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only, more than twice a month).
- •Blood donation \>500 mL within 2 months before inclusion.
- •Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥30 mmHg within 3 minutes when changing from supine to standing position.
- •Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician, except for history of mild allergic diseases which are not active at the time of inclusion and considered not clinically relevant in the opinion of the investigator.
- •History or presence of drug or alcohol abuse.
Arms & Interventions
SAR444336
SAR444336
Intervention: SAR444336
Placebo
placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Part 1: Number of subjects with treatment-emergent adverse events (TEAEs)
Time Frame: Until Day 43
Clinical laboratory evaluations including eosinophils, procalcitonin, and c-reactive protein (CRP), Vital signs, 12-lead electrocardiogram (ECG)
Part 2: Number of subjects with treatment-emergent adverse events (TEAEs)
Time Frame: Until Day 85
Clinical laboratory evaluations including eosinophils, procalcitonin, and c-reactive protein (CRP), Vital signs, 12-lead electrocardiogram (ECG)
Secondary Outcomes
- Plasma PK parameters: tmax(Until Day 29 and Day 85)
- Anti-SAR444336 antibodies(Until Day 29 and Day 85)
- Plasma PK parameters: AUClast(Until Day 29 and Day 85)
- Plasma PK parameters: AUC(Until Day 29 and Day 85)
- Plasma PK parameters: Cmax(Until Day 29 and Day 85)
- Plasma PK parameters: t1/2z(Until Day 29 and Day 85)
- Plasma PK parameters: CL/F(Until Day 29 and Day 85)