HEALEY ALS Platform Trial - Regimen B Verdiperstat

Phase 2

Completed

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.

Recruitment & Eligibility

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. 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.
2. 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.

Arm && Interventions

Group	Intervention	Description
Matching Placebo	Matching Placebo	Matching placebo is administered twice daily p.o. for 24 weeks.
Verdiperstat	Verdiperstat	Verdiperstat is administered twice daily p.o. for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Disease Progression as Assessed by the ALSFRS-R-Slope	Baseline to 24 Weeks	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.
Mortality Even Rate	Baseline to 24 Weeks	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.

Secondary Outcome Measures

Name	Time	Method
Respiratory Function	Baseline to 24 Weeks	Change in respiratory function over time as measured by Slow Vital Capacity (SVC).
Number of Participants That Experienced Death or Death Equivalent	24 Weeks	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.
Muscle Strength	Baseline to 24 Weeks	Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD).

Locations (1): Healey Center for ALS at Mass General
🇺🇸
Boston, Massachusetts, United States