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

Study Purpose:

This is a Phase 1b, multicenter, randomized, placebo-controlled, double-blind study of 28 days, followed by an 18-month open-label extension, designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL343 in participants with amyotrophic lateral sclerosis (ALS)

Study Status:

Not recruiting


Amyotrophic Lateral Sclerosis

Study Type:


Type of Intervention:


Intervention Name:

DNL343, Placebo




Phase 1

Study Chair(s)/Principal Investigator(s):

Linus Sun, MD, PhD, Denali Therapeutics Inc.

Clinicaltrials.gov ID:


Neals Affiliated?


Coordinating Center Contact Information

Centre for Human Drug Research (CHDR)

Leiden, South Holland, Netherlands

Full Study Summary:

This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).

Study Sponsor:

Denali Therapeutics Inc.

Estimated Enrollment:


Estimated Study Start Date:

08 / 11 / 2021

Estimated Study Completion Date:

12 / 01 / 2023

Posting Last Modified Date:

01 / 17 / 2023

Date Study Added to neals.org:

08 / 16 / 2021

Minimum Age:

18 Years

Maximum Age:

80 Years

Can participants use Riluzole?


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


Scottsdale, Arizona 85251
United States

University of California at San Diego

San Diego, California 92093
United States

California Pacific Medical Center

San Francisco, California 94115
United States

PPD Orlando

Orlando, Florida 32806
United States

Emory University

Atlanta, Georgia 30322
United States

Atrium Health Neurosciences Institute

Charlotte, North Carolina 28207
United States

Centre for Human Drug Research (CHDR)

Leiden, South Holland 2333