Clinical trial NCT05795907: Single & Multiple Ascending Dose Study of SAR443820 in Healthy Adult Participants
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis (Healthy Volunteers)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-04-03
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1b with open label study design
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Parts 1a and 1b: Number of participants with adverse events
timeFrame: Day1 up to Day 7 (end of study visit)
measure: Part 2: Number of participants with adverse events
timeFrame: Day1 up to Day 21 (end of study visit)
Secondary outcomes:
measure: Parts 1a and 1b: Assessment of pharmacokinetic parameter of SAR443820: Cmax in plasma
timeFrame: Day1
measure: Parts 1a and 1b: Assessment of pharmacokinetic parameter of SAR443820: tmax in plasma
timeFrame: Day 1
measure: Parts 1a and 1b : Assessment of pharmacokinetic parameter of SAR443820: AUC in plasma
timeFrame: Day1
measure: Parts 1a and 1b : Assessment of pharmacokinetic parameter of SAR443820: t1/2z in plasma
timeFrame: Day1
measure: Part1b: SAR443820 concentrations in cerebrospinal fluid (CSF) samples
timeFrame: Day1
measure: Part 2: Assessment of pharmacokinetic parameter of SAR443820: Cmax in plasma
timeFrame: Day1 and Day14
measure: Part 2: Assessment of pharmacokinetic parameter of SAR443820: tmax in plasma
timeFrame: Day1 and Day14
measure: Part 2: Assessment of pharmacokinetic parameter of SAR443820: AUC tau in plasma
timeFrame: Day1 and Day14
measure: Part 2 Assessment of pharmacokinetic parameter of SAR443820: t1/2z in plasma
timeFrame: Day14
measure: Part 2: Day14/Day1 of 4β-hydroxycholesterol ratio in plasma
timeFrame: Day1 and Day14
Other outcomes:
Locations:
city: Saint Paul
country: United States
facility: Prism Research-Site Number:8400001
state: Minnesota
Study officials:
affiliation: Sanofi
name: Trial Transparency email recommended (Toll free for US & Canada)
role: STUDY_DIRECTOR
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: