Study to Evaluate DNL747 in Subjects With Amyotrophic Lateral Sclerosis

Sanofi

Status and phase: Terminated; Phase 1

Conditions: Amyotrophic Lateral Sclerosis

Treatments: Drug: Placebo; Drug: DNL747

Study type: Interventional

Funder types: Industry

Identifiers

NCT03757351

TDR16536

DNLI-D-0003 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL747 in subjects with Amyotrophic Lateral Sclerosis in a cross-over design

Enrollment: 15 patients

Sex: All

Ages: 21 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria (Double-Blind Part):

• Women of non-childbearing potential and men, aged 21-80 years
• Willingness and ability to complete all aspects of the study; participant should be capable of completing assessments either alone or with help of a caregiver
• 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
• Less than 3 years since symptom onset
• Forced vital capacity (FVC) >50% predicted measured within 30 days of screening
• 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

Key Exclusion Criteria (Double-Blind Part):

• 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
• Unstable or poorly controlled comorbid disease process of any organ system currently requiring active treatment or likely to require treatment adjustment during the study

Key Inclusion Criteria (Open-Label Extension):

• Successful completion of both periods of the the double-blind, crossover part of the study
• Continued 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

Key Exclusion Criteria (Open-Label Extension):

• 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 final follow-up visit as part of the double-blind study period
• New diagnosis of clinically significant neurological disorder (other than frontal temporal lobe dementia)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

15 participants in 3 patient groups

DNL747 First, Placebo Second

Experimental group

Treatment:

Drug: DNL747

Drug: Placebo

Placebo First, DNL747 Second

Experimental group

Treatment:

Drug: DNL747

Drug: Placebo

Open-Label Extension

Experimental group

Description:

Conducted in the Netherlands only.

Treatment:

Drug: DNL747