HEALEY ALS Platform Trial - Regimen B Verdiperstat

• ClinicalTrials.gov Identifier: NCT04436510
• Recruitment Status: Active, not recruiting
• First Posted: June 18, 2020
• Last Update Posted: June 28, 2022
• Sponsor: Merit E. Cudkowicz, MD
• Collaborator: Biohaven Pharmaceuticals, 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 B will evaluate the safety and efficacy of a single study drug, verdiperstat, in participants with ALS.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: Matching Placebo; Drug: Verdiperstat	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 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 167 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 B Verdiperstat
• Actual Study Start Date: July 28, 2020
• Actual Primary Completion Date: April 13, 2022
• Estimated Study Completion Date: April 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Verdiperstat; Verdiperstat is administered twice daily p.o. for 24 weeks.	Drug: Verdiperstat; Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily
Placebo Comparator: Matching Placebo; Matching placebo is administered twice daily p.o. for 24 weeks.	Drug: Matching Placebo; Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily

Outcome Measures

Primary Outcome Measures :

1. Disease Progression [ Time Frame: 24 Weeks ]
   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.

Secondary Outcome Measures :

1. Respiratory Function [ Time Frame: 24 Weeks ]
   Change in respiratory function over time as measured by Slow Vital Capacity (SVC).
2. Muscle Strength [ Time Frame: 24 Weeks ]
   Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD).
3. Survival [ Time Frame: 24 Weeks ]
   Comparison of rate of occurrence between groups.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (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. 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.

Contacts and Locations

Locations

United States, Massachusetts

Healey Center for ALS at Mass General

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Merit E. Cudkowicz, MD

Biohaven Pharmaceuticals, 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: NCT04436510
• Other Study ID Numbers: 2019P003518B
• First Posted: June 18, 2020
• Last Update Posted: June 28, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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; Verdiperstat; Biohaven Pharmaceuticals

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