HEALEY ALS Platform Trial - Regimen G DNL343

Phase 2

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: Matching Placebo; Drug: DNL343

• Registration Number: NCT05842941
• Lead Sponsor: Merit E. Cudkowicz, MD

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.

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 Timeline

• Study First Submitted: 2023-04-24
• Study First Submitted QC: 2023-04-24
• Status Verified: 2023-05
• Study First Posted: 2023-05-06
• Study Start: 2023-05-24
• Last Update Submitted: 2023-05-29
• Last Update Posted: 2023-05-31
• Primary Completion: 2025-07
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Matching Placebo	Matching Placebo	-
DNL343	DNL343	-

Primary Outcome Measures

Name	Time	Method
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

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

Trial Locations

Locations (1)

Healey Center for ALS at Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States