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

Sponsor

Denali Therapeutics Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05006352

Collaborator

(none)

Enrollment

Locations

Arms

27.7

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Aug 11, 2021

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Dec 1, 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

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

Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period [28 Days]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Diagnosis of sporadic or familial ALS
Less than 3 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 or be postmenopausal
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

	Site	City	State	Country	Postal Code
1	HonorHealth	Scottsdale	Arizona	United States	85251
2	University of California at San Diego	San Diego	California	United States	92093
3	California Pacific Medical Center	San Francisco	California	United States	94115
4	PPD Orlando	Orlando	Florida	United States	32806
5	Emory University	Atlanta	Georgia	United States	30322
6	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.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Denali Therapeutics Inc.

ClinicalTrials.gov Identifier:

NCT05006352

Other Study ID Numbers:

DNLI-F-0003
2021-001766-37

First Posted:

Aug 16, 2021

Last Update Posted:

Jun 8, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

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

Study Results

No Results Posted as of Jun 8, 2022