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

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

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 Overview

• Status: Active, not recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: DNL343; Drug: Placebo

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • South Holland
    • Leiden, South Holland, Netherlands, 2333
      • Centre for Human Drug Research (CHDR)
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • HonorHealth
  • California
    • San Diego, California, United States, 92093
      • University of California at San Diego
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Florida
    • Orlando, Florida, United States, 32806
      • PPD Orlando
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Atrium Health Neurosciences Institute

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral repeating dose
Experimental: DNL343 (High Dose)	Drug: DNL343; Oral repeating dose
Experimental: DNL343 (Low Dose)	Drug: DNL343; Oral repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period	28 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
PK parameter: Maximum concentration (Cmax) of DNL343 in plasma	19 months
PK parameter: Time to reach maximum concentration (tmax) of DNL343 in plasma	19 months
PK parameter: Trough concentration (Ctrough) of DNL343 in plasma	19 months
PK parameter: Area under the concentration-time curve from time zero to 24 hours (AUC24) of DNL343 in plasma	19 months
Cerebrospinal fluid-to-plasma concentration ratio of DNL343 following multiple oral doses	19 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2021
• Primary Completion (Actual): December 15, 2022
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: August 7, 2021
• First Submitted That Met QC Criteria: August 13, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Estimate): January 16, 2023
• Last Update Submitted That Met QC Criteria: January 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: ALS
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: DNLI-F-0003; 2021-001766-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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