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
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)