HEALEY ALS Platform Trial - Regimen G DNL343

Sponsor

Merit E. Cudkowicz, MD (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05842941

Collaborator

Denali Therapeutics Inc. (Industry)

240

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: DNL343 Drug: Matching Placebo	Phase 2/Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

HEALEY ALS Platform Trial - Regimen G DNL343

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Aug 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DNL343	Drug: DNL343 DNL343 is administered orally once daily per day for 24 weeks.
Placebo Comparator: Matching Placebo	Drug: Matching Placebo Matching placebo is administered orally once daily per day for 24 weeks.

Arm

Intervention/Treatment

Experimental: DNL343

Drug: DNL343

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

Placebo Comparator: Matching Placebo

Drug: Matching Placebo

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

Outcome Measures

Primary Outcome Measures

Disease Progression [24 Weeks]
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.

Secondary Outcome Measures

Function [24 Weeks]
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.
Combined Assessment of Function and Survival (CAFS) [24 Weeks]
Respiratory Function [24 Weeks]
Change in respiratory function over time as assessed by slow vital capacity (SVC)
Muscle Strength [24 Weeks]
Change in muscle strength over time as measured isometrically using hand-held dynamometry and grip strength
Survival [24 Weeks]
Survival evaluated as time to death or permanent assisted ventilation (PAV)
Survival [24 Weeks]
Survival evaluated as time to death

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

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.