HEALEY ALS Platform Trial - Regimen G DNL343

• ClinicalTrials.gov Identifier: NCT05842941
• Recruitment Status: Enrolling by invitation
• First Posted: May 6, 2023
• Last Update Posted: May 31, 2023
• Sponsor: Merit E. Cudkowicz, MD
• Collaborator: Denali Therapeutics Inc.
• Information provided by (Responsible Party): Merit E. Cudkowicz, MD, Massachusetts General Hospital

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 (Clinical Trial)
• Estimated 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
• Actual Study Start Date: May 24, 2023
• Estimated Primary Completion Date: July 2025
• Estimated Study Completion Date: August 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.

Outcome Measures

Primary Outcome Measures :

1. Disease Progression [ Time Frame: 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 :

1. Function [ Time Frame: 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.
2. Combined Assessment of Function and Survival (CAFS) [ Time Frame: 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.

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Massachusetts

Healey Center for ALS at Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Merit E. Cudkowicz, MD

Denali Therapeutics Inc.

Investigators

• Principal Investigator: Merit Cudkowicz, MD; Massachusetts General Hospital

More Information

• Responsible Party: Merit E. Cudkowicz, MD, Chief, Neurology Department, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT05842941
• Other Study ID Numbers: 2019P003518G
• First Posted: May 6, 2023
• Last Update Posted: May 31, 2023
• Last Verified: May 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merit E. Cudkowicz, MD, Massachusetts General Hospital:

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

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases