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

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.

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).

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis (Healthy Volunteers)
• Intervention / Treatment: Drug: SAR443820; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55144
      • Prism Research-Site Number:8400001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Trial Transparency email recommended (Toll free for US & Canada), Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Actual): July 20, 2021
• Study Completion (Actual): July 20, 2021

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: March 21, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: TDU16519-TDR16520; U1111-1254-0034 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No