A Phase 1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study, Followed by an Open-Label Extension, to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis

Minimum Age:

18 Years

Maximum Age:

80 Years

Can participants use Riluzole?

Yes

Key Inclusion Criteria:

- Diagnosis of sporadic or familial ALS

- ≤ 4 years since ALS symptom onset

- Stable doses of approved ALS treatments (riluzole and/or edaravone) for at least 2 months prior to screening

- Participants must be able to swallow the study intervention

- Vital capacity >50% predicted at screening

- Women must have been surgically sterilized, be postmenopausal, or for participants of childbearing potential, must not be pregnant, and both the participant and the male partner must use highly effective contraception

- Men, and sex partner if a woman of childbearing potential, must use highly effective contraception

Key Exclusion Criteria:

- Any history of unstable or poorly controlled psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders

- Positive serum pregnancy test or currently lactating or breastfeeding

- History of malignancy within 5 years

- History of clinically significant neurologic disorders other than ALS