A Multicenter, Randomized, Placebo-Controlled, Double-Blind Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SAR443060 in Subjects with Amyotrophic Lateral Sclerosis (ALS)

Completed

• Conditions: Amyotrophic Lateral Sclerosis (ALS); motor neurone disease; 10029317

• Registration Number: NL-OMON49740
• Lead Sponsor: Sanofi-aventis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2021-02-07
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 16

Inclusion Criteria

Double-blinded part:
6) Diagnosis of laboratory-supported probable, probable, or definite (sporadic
or familial) ALS according to the El Escorial World Federation of Neurology
revised research diagnostic criteria (Ludolph et al. 2015;)
7) Less than 3 years since symptom onset
8) Forced vital capacity (FVC) >50% predicted measured within 30 days of
screening
9) If subject is taking approved ALS treatments (riluzole and/or edaravone),
doses must be stable for >=2 months prior to screening and subject is expected
to stay on a stable regimen throughout the study.
11) Subjects must be able to swallow the study capsules.
Open Label Extension:
1) Successful completion of both periods of the double-blind, crossover part of
this study within 12 months of anticipated first dose of OLE
2) Body weight of at least 45 kg
6) Stable prescription medications including riluzole and/or edaravone for >= 1
month. New prescription medications or changes to existing medications during
this trial period are allowed with investigator discretion.
7) Subjects must either be able to swallow the study capsules (thickening
agents to assist in swallowing are permitted) or have a G-tube in place and are
able to administer study drug through G-tube either independently or with help
via a caregiver.

Exclusion Criteria

Double-blinded part:
1) Unstable or poorly controlled comorbid disease process of any organ system
currently requiring active treatment or likely to require treatment adjustment
during the study, as assessed by the investigator or Sponsor
2) History of a clinically significant non-ALS neurologic disorder (other than
frontal temporal lobe dementia), including, but not limited to, muscular
dystrophy, spinal stenosis, peripheral neuropathy, inherited neuropathies, AD,
Parkinson*s disease, Lewy body dementia, vascular dementia, Huntington*s
disease, epilepsy, stroke, multiple sclerosis, brain tumor, or brain infection
or abscess
3) History of head trauma resulting in loss of consciousness or clinically
significant concussion within 1 year before screening, or any head trauma that
resulted in permanent neurologic deficit
4) Clinical laboratory test values outside the normal range at screening,
unless assessed by the investigator and CRO medical monitor as clinically
acceptable or as specified in other exclusion criteria below
21) Use of or intention to use any prohibited prescription or over-the-counter
(OTC) medication (including vitamin/mineral supplements and herbal medicines
such as St. John*s Wort) that is a moderate to strong CYP3A inducer or
inhibitor within 7 days or 5 half-lives (whichever is longer) of the first dose
administration or anticipated use through the follow-up visit. Note: other
medications are permitted if subject is on a stable regimen for at least 30
days before first dose administration. Nonsystemic medications (e.g., topical
medications unlikely to achieve meaningful plasma exposure), subcutaneous
lidocaine, paracetamol, and caffeine for treatment of post-LP headache, and
medications needed to treat AEs and medical emergencies are permitted. Other
medication may also be permitted if jointly agreed to by both investigator and
Sponsor.
22) Use of anticoagulation, daily aspirin >100 mg, or anti-platelet medications
within 5 half-lives before the first administration of study drug or
anticipated need for these medications through the final follow-up visit. Note:
the use of OTC nonsteroidal anti-inflammatory drugs (NSAIDs) at doses specified
in the OTC drug label for less than 3 consecutive days is permitted.
23) History of bleeding disorders included but not limited to thrombocytopenia
(defined as platelets <140,000/µL), von Willebrand disease, hemophilia, and
other factor deficiencies
Open Label Extension:
1) Presence of laboratory abnormalities, physical examination findings, or AEs
determined to be clinically significant by the investigator from the
double-blind part of the study that have not resolved by the FFU visit
2) For subjects who completed the double-blind part of the study >14 days prior
to start of OLE, presence of clinical laboratory test values outside the normal
range at OLE screening, significant physical examination abnormalities, or
persistent AEs from the double-blind part of the study, unless assessed by the
investigator as clinically acceptable
3) New diagnosis of a clinically significant non-ALS neurologic disorder (other
than frontal temporal lobe dementia), including, but not limited to: muscular
dystrophy, spinal stenosis, peripheral neuropathy, inherited neuropathies, AD,
Parkinson*s disease, Lewy body demen

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Safety and tolerability:<br /><br>AEs, clinical laboratory evaluations (hematology, clinical chemistry,<br /><br>urinalysis), 12 lead ECGs, vital sign measurements, and physical examinations.<br /><br><br /><br>Responses obtained from the Columbia-Suicide Severity Rating Scale (C-SSRS)<br /><br>will also be used to derive a category for suicidality according to the<br /><br>Columbia Classification of Suicide Assessment (C-CASA).</p><br>