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

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

Study Description

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.).

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

Denali Therapeutics Inc.

Investigators

• Study Director: Linus Sun, MD, PhD; Denali Therapeutics Inc.

More Information

• 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
• 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

Keywords provided by Denali Therapeutics Inc.:

ALS

Additional relevant MeSH terms:

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