NCT05006352

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)

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
29

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Aug 2021

Typical duration for phase_1

Geographic Reach
2 countries

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 7, 2021

Completed
4 days until next milestone

Study Start

First participant enrolled

August 11, 2021

Completed
5 days until next milestone

First Posted

Study publicly available on registry

August 16, 2021

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 15, 2022

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 5, 2024

Completed
Last Updated

September 19, 2024

Status Verified

September 1, 2024

Enrollment Period

1.3 years

First QC Date

August 7, 2021

Last Update Submit

September 12, 2024

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS

Outcome Measures

Primary Outcomes (1)

  • Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period

    28 Days

Secondary Outcomes (5)

  • 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

Study Arms (3)

DNL343 (High Dose)

EXPERIMENTAL
Drug: DNL343

DNL343 (Low Dose)

EXPERIMENTAL
Drug: DNL343

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

DNL343DRUG

Oral repeating dose

DNL343 (High Dose)DNL343 (Low Dose)
PlaceboDRUG

Oral repeating dose

Placebo

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

HonorHealth

Scottsdale, Arizona, 85251, United States

Location

University of California at San Diego

San Diego, California, 92093, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

PPD Orlando

Orlando, Florida, 32806, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Atrium Health Neurosciences Institute

Charlotte, North Carolina, 28207, United States

Location

Centre for Human Drug Research (CHDR)

Leiden, South Holland, 2333, Netherlands

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesMotor Neuron DiseaseNeurodegenerative DiseasesTDP-43 ProteinopathiesNeuromuscular DiseasesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Linus Sun, MD, PhD

    Denali Therapeutics Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 7, 2021

First Posted

August 16, 2021

Study Start

August 11, 2021

Primary Completion

December 15, 2022

Study Completion

June 5, 2024

Last Updated

September 19, 2024

Record last verified: 2024-09

Data Sharing

IPD Sharing
Will not share

Locations

US(6)NL(1)