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

Phase 1

Active, not recruiting

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: Placebo; Drug: DNL343

• Registration Number: NCT05006352
• Lead Sponsor: 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)

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 Timeline

• Study First Submitted: 2021-08-07
• Study Start: 2021-08-11
• Study First Submitted QC: 2021-08-13
• Study First Posted: 2021-08-16
• Primary Completion: 2022-12-15
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-13
• Last Update Posted: 2023-01-17
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 30

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
DNL343 (High Dose)	DNL343	-
DNL343 (Low Dose)	DNL343	-

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period	28 Days

Secondary Outcome Measures

Name	Time	Method
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
PK parameter: Maximum concentration (Cmax) of DNL343 in plasma	19 months
Cerebrospinal fluid-to-plasma concentration ratio of DNL343 following multiple oral doses	19 months
PK parameter: Time to reach maximum concentration (tmax) of DNL343 in plasma	19 months

Trial Locations

Locations (7)

Emory University; 🇺🇸 Atlanta, Georgia, United States

Atrium Health Neurosciences Institute; 🇺🇸 Charlotte, North Carolina, United States

PPD Orlando; 🇺🇸 Orlando, Florida, United States

HonorHealth; 🇺🇸 Scottsdale, Arizona, United States

Centre for Human Drug Research (CHDR); 🇳🇱 Leiden, South Holland, Netherlands

University of California at San Diego; 🇺🇸 San Diego, California, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States