Single & Multiple Ascending Dose Study of SAR443820 in Healthy Adult Participants

Study Overview
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Brief Summary
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This is a Phase 1, single-center study conducted in 2 parts: Part 1a, single ascending dose (SAD-TDU16519): Double-blind, randomized, placebo-controlled sequential ascending single oral doses including up to 6 cohorts. Each cohort will include 8 participants (6 receiving SAR443820 and 2 placebo). Part 1b (TDU16519): - Open label, single SAR443820 dose in one or two separated cohort(s) for SAR443820 measurements in CSF and in plasma. Part 2, multiple ascending dose (MAD -TDR16520): Double-blind, randomized, placebo-controlled, sequential ascending repeated oral doses for 14 days, including up to 4 cohorts. Each cohort will include 10 participants (8 receiving SAR443820 and 2 placebo).

Detailed Description
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The duration of the study for a participant will include: Screening Period: up to 28 days Part 1a: Treatment in fasted condition: 1 day (Day 1). Study observation Period from Day -2/Day -1 to Day 3. Follow-up with the end of study: from Day 5 to Day 7. Total duration from screening per participant: up to 5 weeks. Part 1b: Treatment in fed condition: 1 day (Day 1). Study observation Period from Day -1/Day1 to Day 2. Follow-up with the end of study: from Day 5 to Day 7. Total duration from screening per participant: up to 5 weeks. Part 2: Treatment: 14 days (Day 1 to Day 14). Study observation Period from Day -2/Day -1 to Day 17. Follow-up with the end of study: from Day 19 to Day 21. Total duration from screening per participant: up to 7 weeks.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics of Ascending Single and 14-day Repeated Oral Doses of SAR443820 in Healthy Adult Participants.

Conditions
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Amyotrophic Lateral Sclerosis (Healthy Volunteers)

Intervention / Treatment
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* Drug: SAR443820
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and/or female participant, between 18 and 55 years of age, inclusive. Body weight between 50.0 and 100.0 kg, inclusive, if male, and between 40.0 and 90.0 kg, inclusive, if female, body mass index between 18.0 and 30.0 kg/m2, inclusive. Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination). Having given written informed consent prior to undertaking any study-related procedure. Not under any administrative or legal supervision or under institutionalization due to regulatory or juridical order. Exclusion Criteria: Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteo-muscular, articular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness. Personal medical history of seizure. Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month). Any medication (including St John's Wort) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, with the exception of hormonal contraception or menopausal hormone replacement therapy; any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion. Positive result for hepatitis B, C or HIV Positive result on urine drug screen Positive alcohol test. Any consumption of citrus fruits or their juices within 5 days before inclusion. Current psychiatric disorder, suicidal ideation in the previous 6 months (as assessed by the C-SSRS), or a lifetime suicide attempt. Additional exclusion criteria applied, and specially for Part 1b, criteria related to the study procedure of lumbar puncture. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1b with open label study design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR443820<br>Single dose oral ascending dose (parts 1a and 1b) and multiple ascending oral dose (part 2) of SAR443820 | Drug: SAR443820<br>* Capsule / Oral<br>|
| Placebo Comparator: Placebo<br>Single dose oral ascending dose (part 1a) and multiple ascending oral dose (part 2) of matching placebo | Drug: Placebo<br>* Matching Capsule / Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1a and 1b: Number of participants with adverse events |  | Day1 up to Day 7 (end of study visit) | 
| Part 2: Number of participants with adverse events |  | Day1 up to Day 21 (end of study visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1a and 1b: Assessment of pharmacokinetic parameter of SAR443820: Cmax in plasma | Parts 1a and 1b: Maximum plasma concentration | Day1 | 
| Parts 1a and 1b: Assessment of pharmacokinetic parameter of SAR443820: tmax in plasma | Parts 1a and 1b: time to reach Cmax | Day 1 | 
| Parts 1a and 1b : Assessment of pharmacokinetic parameter of SAR443820: AUC in plasma | Parts 1a and 1b: Area under the plasma concentration versus time | Day1 | 
| Parts 1a and 1b : Assessment of pharmacokinetic parameter of SAR443820: t1/2z in plasma | Terminal half-life in plasma | Day1 | 
| Part1b: SAR443820 concentrations in cerebrospinal fluid (CSF) samples | Part 1b: CSF to plasma concentration ratio | Day1 | 
| Part 2: Assessment of pharmacokinetic parameter of SAR443820: Cmax in plasma | Part 2: Maximum plasma concentration | Day1 and Day14 | 
| Part 2: Assessment of pharmacokinetic parameter of SAR443820: tmax in plasma | Part 2: Time to reach Cmax | Day1 and Day14 | 
| Part 2: Assessment of pharmacokinetic parameter of SAR443820: AUC tau in plasma | Part 2: Area under the plasma concentration versus time during a dosing interval | Day1 and Day14 | 
| Part 2 Assessment of pharmacokinetic parameter of SAR443820: t1/2z in plasma | Terminal half-life in plasma | Day14 | 
| Part 2: Day14/Day1 of 4β-hydroxycholesterol ratio in plasma | D14/D1 of 4β-hydroxycholesterol ratio | Day1 and Day14 |