HEALEY ALS Platform Trial - Regimen D Pridopidine

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 D will evaluate the safety and efficacy of a single study drug, pridopidine, 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 D Pridopidine, the participant will complete a screening visit to assess additional Regimen D eligibility criteria. Once Regimen D eligibility criteria are confirmed, participants will complete a baseline assessment and be randomized in a 3:1 ratio to either active pridopidine or matching placebo. Regimen D will enroll by invitation, as participants may not choose to enroll in Regimen D. 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 D. 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 D Pridopidine

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Pridopidine
* 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). Participants with a confirmed prolonged Fridericia-corrected QT (QTcF) interval (defined as a QTcF interval of >450 ms for men and >470 ms for women). Participants with clinically significant heart disease, clinically significant history of arrhythmia, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia, or presence of left bundle branch block. Participants with known history of long QT syndrome or a first degree relative with this condition. Participants using prohibited medications within the 4 weeks prior to the Regimen Specific Screening Visit, as detailed in section 5.9. Participants using the following medications at the time of the Regimen Specific Screening Visit: Nuedexta - at a dosage higher than 20 mg dextromethorphan + 10 mg quinidine BID Citalopram - at a dosage higher than 20 mg/day Escitalopram - at a dosage higher than 10 mg/day Participants with a known allergy to any ingredient of the study intervention (pridopidine, silicified microcrystalline cellulose, and magnesium stearate).

Ages Eligible for Study
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Minimum Age: 18 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: Pridopidine<br>Pridopidine is administered orally twice daily for 24 weeks. | Drug: Pridopidine<br>* Administration: Oral Dose: 45mg twice daily<br>|
| Placebo Comparator: Matching Placebo<br>Matching placebo is administered orally twice daily for 24 weeks. | Drug: Matching Placebo<br>* Administration: Oral Dose: one capsule twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Progression as Assessed by the ALSFRS-R Total Score | Change in disease severity over time as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). 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. | Baseline to 24 Weeks | 
| Mortality Event Rate | Mortality is defined as death or death equivalent. A participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row. The rate of mortality was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times. | Baseline to 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bulbar Function in Participants With Bulbar Dysfunction at Baseline | Change in bulbar function over time in participants with bulbar dysfunction at baseline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) bulbar subdomain. Each question is scored from 4 (normal) to 0 (no ability), with a maximum total score of 12 and a minimum total score of 0 for the bulbar subdomain. Patients with higher scores have more bulbar function. Participants were classified as having bulbar dysfunction at baseline if their score on the ALSFRS-R bulbar domain (Q1-Q3) score was less than 12. | Baseline to 24 Weeks | 
| Bulbar Function in All Randomized Participants | Change in bulbar function over time in all randomized participants as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) bulbar subdomain. Each question is scored from 4 (normal) to 0 (no ability), with a maximum total score of 12 and a minimum total score of 0 for the bulbar subdomain. Patients with higher scores have more bulbar function. | Baseline to 24 Weeks | 
| Respiratory Function | Change in respiratory function over time as measured by Slow Vital Capacity (SVC). | Baseline to 24 Weeks | 
| Bulbar Function in Participants With Rapid Pre-baseline Progression | Change in bulbar function over time in participants with rapid pre-baseline progression as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) bulbar subdomain. Each question is scored from 4 (normal) to 0 (no ability), with a maximum total score of 12 and a minimum total score of 0 for the bulbar subdomain. Patients with higher scores have more bulbar function. Participants were classified with rapid pre-baseline progression if their change in ALSFRS-R total score between Master Protocol Screening and Regimen Baseline was greater than or equal or 0.75 points per month. | Baseline to 24 Weeks | 
| Time to Bulbar Decline | Time to first decline of 1-point or greater post baseline in the ALSFRS-R bulbar domain score among all participants. Analysis performed using interval-censored survival analysis. Results presented as median interval (upper & lower bounded) time to event. | Baseline to 24 Weeks | 
| Muscle Strength | Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD). | Baseline to 24 Weeks | 
| Number of Participants That Experienced Death or Death Equivalent | The number of participants who died or met the criterion for a death equivalent from the date of their baseline visit to the end of the Week 24visit window (generally 175 days after baseline). The death equivalent criterion is use of permanent assisted ventilation (PAV) for more than 22 hours per day for more than 7 days in a row. | Baseline to 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, Pridopidine, Prilenia Therapeutics