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A Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis

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. Identifier: NCT05006352
Recruitment Status : Active, not recruiting
First Posted : August 16, 2021
Last Update Posted : January 17, 2023
Information provided by (Responsible Party):
Denali Therapeutics Inc.

Brief Summary:
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)

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: DNL343 Drug: Placebo Phase 1

Detailed Description:
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.).

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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

Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period [ Time Frame: 28 Days ]

Secondary Outcome Measures :
  1. PK parameter: Maximum concentration (Cmax) of DNL343 in plasma [ Time Frame: 19 months ]
  2. PK parameter: Time to reach maximum concentration (tmax) of DNL343 in plasma [ Time Frame: 19 months ]
  3. PK parameter: Trough concentration (Ctrough) of DNL343 in plasma [ Time Frame: 19 months ]
  4. PK parameter: Area under the concentration-time curve from time zero to 24 hours (AUC24) of DNL343 in plasma [ Time Frame: 19 months ]
  5. Cerebrospinal fluid-to-plasma concentration ratio of DNL343 following multiple oral doses [ Time Frame: 19 months ]

Information from the National Library of Medicine

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.

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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

Information from the National Library of Medicine

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 identifier (NCT number): NCT05006352

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United States, Arizona
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
Centre for Human Drug Research (CHDR)
Leiden, South Holland, Netherlands, 2333
Sponsors and Collaborators
Denali Therapeutics Inc.
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Study Director: Linus Sun, MD, PhD Denali Therapeutics Inc.
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Responsible Party: Denali Therapeutics Inc. 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

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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
Keywords provided by Denali Therapeutics Inc.:
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases