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

Amyotrophic Lateral Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05006352
• Other study ID #: DNLI-F-0003
• Secondary ID: 2021-001766-37
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 11, 2021
• Est. completion date: December 2023

Study information

• Verified date: January 2023
• Source: Denali Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 2023
• Est. primary completion date: December 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• DNL343
Oral repeating dose
• Placebo
Oral repeating dose

Locations

Country	Name	City	State
Netherlands	Centre for Human Drug Research (CHDR)	Leiden	South Holland
United States	Emory University	Atlanta	Georgia
United States	Atrium Health Neurosciences Institute	Charlotte	North Carolina
United States	PPD Orlando	Orlando	Florida
United States	University of California at San Diego	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	HonorHealth	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Denali Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period		28 Days
Secondary	PK parameter: Maximum concentration (Cmax) of DNL343 in plasma		19 months
Secondary	PK parameter: Time to reach maximum concentration (tmax) of DNL343 in plasma		19 months
Secondary	PK parameter: Trough concentration (Ctrough) of DNL343 in plasma		19 months
Secondary	PK parameter: Area under the concentration-time curve from time zero to 24 hours (AUC24) of DNL343 in plasma		19 months
Secondary	Cerebrospinal fluid-to-plasma concentration ratio of DNL343 following multiple oral doses		19 months