HEALEY ALS Platform Trial - Regimen G DNL343

NCT05842941 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2019P003518G
• Study Type: interventional
• Target: 249
• Locations: 1 country
• Sites: 1

Brief Summary

The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS. Regimen G will evaluate the safety and efficacy of a single study drug, DNL343, in participants with ALS.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Placebo-Controlled; Double-Blind; Regimen Specific Appendix; Lou Gehrig's Disease; DNL343; Denali Therapeutics

Outcome Measures

Primary Outcomes (2)

• Disease Progression as Assessed by the ALSFRS-R-Slope

  Change in disease severity as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) total score using a Bayesian repeated measures model that accounts for loss to follow-up due to mortality. Each of 12 questions assessing distinct functional ability is scored from 4(normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Participants with higher scores have more physical function. Note that only participants who survived to their Week 24 visit contribute to the estimate.

  Baseline to 24 Weeks

• Mortality Event Rate

  The Mortality Rate, presented as mean deaths per month, was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times. Mortality is defined as death or death equivalent. A participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row.

  Baseline to 24 weeks

Secondary Outcomes (7)

• ALSFRS-R Total Score

  Baseline to 24 Weeks

• Combined Assessment of Function and Survival (CAFS)

  Baseline to 24 Weeks

• Respiratory Function

  Baseline to 24 Weeks

• Upper Limb Muscle Strength

  24 weeks

• Number of Participants With Death or Permanent Assisted Ventilation (PAV)

  Baseline to 24 weeks

Study Arms (2)

DNL343

EXPERIMENTAL

Drug: DNL343

Matching Placebo

PLACEBO COMPARATOR

Drug: Matching Placebo

Interventions

DNL343 DRUG

DNL343 is administered orally once daily per day for 24 weeks.

DNL343

Matching Placebo DRUG

Matching placebo is administered orally once daily per day for 24 weeks.

Matching Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Diagnosis of epilepsy or seizure within 6 months of randomization
• Hypersensitivity to DNL343 or any of the excipients contained within the DNL343 drug product
• The concomitant use of prescription or over-the-counter (OTC) medications that are inducers of certain cytochrome P450 enzymes, substrates of certain cytochrome P450 enzymes, or substrates of certain drug transporters.

Sponsors & Collaborators

• Denali Therapeutics Inc.: collaborator
• Merit E. Cudkowicz, MD: lead

Study Sites (1)

Healey Center for ALS at Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Healey Center for ALS Project Management
• Organization: Healey Center for ALS at Massachusetts General Hospital

healeyalsplatform@mgh.harvard.edu

833-425-8257 (HALT ALS)

Study Officials

• Merit Cudkowicz, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Neurology Department

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: May 6, 2023
• Study Start: May 24, 2023
• Primary Completion: October 29, 2024
• Study Completion: October 29, 2024
• Last Updated: January 28, 2026
• Results First Posted: January 28, 2026

Record last verified: 2025-12

Locations

US (1)