A Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT05006352 |
Recruitment Status :
Active, not recruiting
First Posted : August 16, 2021
Last Update Posted : January 17, 2023
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Amyotrophic Lateral Sclerosis | Drug: DNL343 Drug: Placebo | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 30 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | August 11, 2021 |
Actual Primary Completion Date : | December 15, 2022 |
Estimated Study Completion Date : | December 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: DNL343 (High Dose) |
Drug: DNL343
Oral repeating dose |
Experimental: DNL343 (Low Dose) |
Drug: DNL343
Oral repeating dose |
Placebo Comparator: Placebo |
Drug: Placebo
Oral repeating dose |
- Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period [ Time Frame: 28 Days ]
- PK parameter: Maximum concentration (Cmax) of DNL343 in plasma [ Time Frame: 19 months ]
- PK parameter: Time to reach maximum concentration (tmax) of DNL343 in plasma [ Time Frame: 19 months ]
- PK parameter: Trough concentration (Ctrough) of DNL343 in plasma [ Time Frame: 19 months ]
- PK parameter: Area under the concentration-time curve from time zero to 24 hours (AUC24) of DNL343 in plasma [ Time Frame: 19 months ]
- Cerebrospinal fluid-to-plasma concentration ratio of DNL343 following multiple oral doses [ Time Frame: 19 months ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05006352
United States, Arizona | |
HonorHealth | |
Scottsdale, Arizona, United States, 85251 | |
United States, California | |
University of California at San Diego | |
San Diego, California, United States, 92093 | |
California Pacific Medical Center | |
San Francisco, California, United States, 94115 | |
United States, Florida | |
PPD Orlando | |
Orlando, Florida, United States, 32806 | |
United States, Georgia | |
Emory University | |
Atlanta, Georgia, United States, 30322 | |
United States, North Carolina | |
Atrium Health Neurosciences Institute | |
Charlotte, North Carolina, United States, 28207 | |
Netherlands | |
Centre for Human Drug Research (CHDR) | |
Leiden, South Holland, Netherlands, 2333 |
Study Director: | Linus Sun, MD, PhD | Denali Therapeutics Inc. |
Responsible Party: | Denali Therapeutics Inc. |
ClinicalTrials.gov Identifier: | NCT05006352 |
Other Study ID Numbers: |
DNLI-F-0003 2021-001766-37 ( EudraCT Number ) |
First Posted: | August 16, 2021 Key Record Dates |
Last Update Posted: | January 17, 2023 |
Last Verified: | January 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | Yes |
ALS |
Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases |
Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases |