HEALEY ALS Platform Trial - Regimen B Verdiperstat

Study Overview
=================
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 B will evaluate the safety and efficacy of a single study drug, verdiperstat, 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 B - Verdiperstat, the participant will complete a screening visit to assess additional Regimen B eligibility criteria. Once Regimen B eligibility criteria are confirmed, participants will complete a baseline assessment and be randomized in a 3:1 ratio to either active Verdiperstat or matching placebo. Regimen B will enroll by invitation as participants may not choose to enroll in Regimen B. 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 B. For a list of enrolling sites, please see the HEALEY ALS Platform Trial Master Protocol under NCT04297683.

Official Title
-----------------
HEALEY ALS Platform Trial - Regimen B Verdiperstat

Conditions
-----------------
Amyotrophic Lateral Sclerosis

Intervention / Treatment
-----------------
* Drug: Matching Placebo
* Drug: Verdiperstat


Participation Criteria
=================
Eligibility 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). Participants who are taking strong inhibitors of CYP1A2 (i.e., ciprofloxacin, enoxacin, fluvoxamine, zafirlukast) for chronic/long-term use defined as more than two weeks. Participants who are taking strong inhibitors of CYP3A4 (i.e., conivaptan, itraconazole, ketoconazole, posaconazole, troleandomycin, voriconazole, clarithromycin, diltiazem, idelalisib, nefazodone, and certain antiviral agents [cobicistat, danoprevir, ritonavir, elvitegravir, indinavir, lopinavir, paritaprevir, ombitasavir, dasabuvir, saquinavir, tipranavir, nelfinavir]) for chronic/long-term use defined as more than two weeks. Note: Topical antifungal use is not exclusionary. Participants should not consume large quantities of grapefruit juice (more than 8oz per day) on a regular basis.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verdiperstat<br>Verdiperstat is administered twice daily p.o. for 24 weeks. | Drug: Verdiperstat<br>* Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily<br>|
| Placebo Comparator: Matching Placebo<br>Matching placebo is administered twice daily p.o. for 24 weeks. | Drug: Matching Placebo<br>* Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Progression as Assessed by the ALSFRS-R-Slope | Change in disease severity as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) total score using a Bayesian repeated measures model that accounts for loss to follow-up due to mortality. Each of 12 questions assessing distinct functional ability 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 Even 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 |
| --- | --- | --- |
| Respiratory Function | Change in respiratory function over time as measured by Slow Vital Capacity (SVC). | 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 24 visit 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. | 24 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ALS, Placebo-Controlled, Double-Blind, Regimen Specific Appendix, Lou Gehrig's Disease, Verdiperstat, Biohaven Pharmaceuticals