HEALEY ALS Platform Trial - Regimen G DNL343

Study Overview
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Brief Summary
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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
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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.

Official Title
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HEALEY ALS Platform Trial - Regimen G DNL343

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: DNL343
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DNL343<br> | Drug: DNL343<br>* DNL343 is administered orally once daily per day for 24 weeks.<br>|
| Placebo Comparator: Matching Placebo<br> | Drug: Matching Placebo<br>* Matching placebo is administered orally once daily per day for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Respiratory Function | Change in respiratory function over time as assessed by slow vital capacity (SVC) | 24 Weeks | 
| Muscle Strength | Change in muscle strength over time as measured isometrically using hand-held dynamometry and grip strength | 24 Weeks | 
| Survival | Survival evaluated as time to death or permanent assisted ventilation (PAV) | 24 Weeks | 
| Survival | Survival evaluated as time to death | 24 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, Placebo-Controlled, Double-Blind, Regimen Specific Appendix, Lou Gehrig's Disease, DNL343, Denali Therapeutics