HEALEY ALS Platform Trial - Regimen G DNL343

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

HEALEY ALS Platform Trial - Regimen G DNL343

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05842941
• Other study ID #: 2019P003518G
• Status: Enrolling by invitation
• Phase: Phase 2/Phase 3
• Start date: May 24, 2023
• Est. completion date: August 2025

Study information

• Verified date: May 2023
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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. This trial is designed as a perpetual platform trial. This means that there is a single Master Protocol dictating the conduct of the trial. The HEALEY ALS Platform Trial Master Protocol is registered as NCT04297683. Once a participant enrolls into the Master Protocol and meets all eligibility criteria, the participant will be eligible to be randomized into any currently enrolling regimen. All participants will have an equal chance of being randomized to any currently enrolling regimen. If a participant is randomized to Regimen G DNL343, the participant will complete a screening visit to assess additional Regimen G eligibility criteria. Once Regimen G eligibility criteria are confirmed, participants will complete a baseline assessment and be randomized in a 3:1 ratio to either active DNL343 or matching placebo. Regimen G will enroll by invitation, as participants may not choose to enroll in Regimen G. Participants must first enroll into the Master Protocol and be eligible to participate in the Master Protocol before being able to be randomly assigned to Regimen G. For a list of enrolling sites, please see the HEALEY ALS Platform Trial Master Protocol under NCT04297683.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 240
• Est. completion date: August 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• No additional inclusion criteria beyond the inclusion criteria specified in the Master Protocol (NCT NCT04297683).

Exclusion Criteria:

• The following exclusion criteria are in addition to the exclusion criteria specified in the Master Protocol (NCT NCT04297683).

1. Diagnosis of epilepsy or seizure within 6 months of randomization

2. Hypersensitivity to DNL343 or any of the excipients contained within the DNL343 drug product

3. 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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

Drug:
• DNL343
DNL343 is administered orally once daily per day for 24 weeks.
• Matching Placebo
Matching placebo is administered orally once daily per day for 24 weeks.

Locations

Country	Name	City	State
United States	Healey Center for ALS at Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Merit E. Cudkowicz, MD	Denali Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Progression	Change in disease severity over time as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score and survival. Each type of function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Patients with higher scores have more physical function.	24 Weeks
Secondary	Function	Change in ALSFRS-R total score over time. Each type of function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Patients with higher scores have more physical function.	24 Weeks
Secondary	Combined Assessment of Function and Survival (CAFS)	Combined assessment of function and survival uses ALSFRS-R total score as the function measure and death or permanent assisted ventilation as the survival component.; The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score and survival. Each type of function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Patients with higher scores have more physical function.	24 Weeks
Secondary	Respiratory Function	Change in respiratory function over time as assessed by slow vital capacity (SVC)	24 Weeks
Secondary	Muscle Strength	Change in muscle strength over time as measured isometrically using hand-held dynamometry and grip strength	24 Weeks
Secondary	Survival	Survival evaluated as time to death or permanent assisted ventilation (PAV)	24 Weeks
Secondary	Survival	Survival evaluated as time to death	24 Weeks