HEALEY ALS Platform Trial - Regimen D Pridopidine

• ClinicalTrials.gov Identifier: NCT04615923
• Recruitment Status: Active, not recruiting
• First Posted: November 4, 2020
• Last Update Posted: May 17, 2023
• Sponsor: Merit E. Cudkowicz, MD
• Collaborator: Prilenia Therapeutics
• 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 D will evaluate the safety and efficacy of a single study drug, pridopidine, in participants with ALS.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 163 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 D Pridopidine
• Actual Study Start Date: December 18, 2020
• Actual Primary Completion Date: July 14, 2022
• Estimated Study Completion Date: June 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pridopidine; Pridopidine is administered orally twice daily for 24 weeks.	Drug: Pridopidine; Administration: Oral Dose: 45mg twice daily
Placebo Comparator: Matching Placebo; Matching placebo is administered orally twice daily for 24 weeks.	Drug: Matching Placebo; Administration: Oral Dose: one capsule 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. Bulbar Function in Participants with Bulbar Dysfunction [ Time Frame: 24 Weeks ]
   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.
2. Bulbar Function in all Randomized Participants [ Time Frame: 24 Weeks ]
   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.
3. Speech [ Time Frame: 24 Weeks ]
   Change in speech over time as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) speech subdomain. The speech question is scored from 4 (normal) to 0 (no ability), with a maximum total score of 4 and a minimum total score of 0. Patients with higher scores have better speech.
4. Respiratory Function [ Time Frame: 24 Weeks ]
   Change in respiratory function over time as measured by Slow Vital Capacity (SVC).
5. Bulbar Function in Participants with Rapid pre-baseline Progression [ Time Frame: 24 Weeks ]
   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.
6. Time to Bulbar Dysfunction [ Time Frame: 24 Weeks ]
   Time from baseline to the first observed bulbar dysfunction as measured by an ALS Functional Rating Scale-Revised (ALSFRS-R) bulbar subdomain score of less than 12.
7. Muscle Strength [ Time Frame: 24 Weeks ]
   Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD).
8. 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 with a confirmed prolonged Fridericia-corrected QT (QTcF) interval (defined as a QTcF interval of >450 ms for men and >470 ms for women).
  2. 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.
  3. Participants with known history of long QT syndrome or a first degree relative with this condition.
  4. Participants using prohibited medications within the 4 weeks prior to the Regimen Specific Screening Visit, as detailed in section 5.9.

  5. Participants using the following medications at the time of the Regimen Specific Screening Visit:

     1. Nuedexta - at a dosage higher than 20 mg dextromethorphan + 10 mg quinidine BID
     2. Citalopram - at a dosage higher than 20 mg/day
     3. Escitalopram - at a dosage higher than 10 mg/day
  6. Participants with a known allergy to any ingredient of the study intervention (pridopidine, silicified microcrystalline cellulose, and magnesium stearate).

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

Prilenia Therapeutics

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: NCT04615923
• Other Study ID Numbers: 2019P003518D
• First Posted: November 4, 2020
• Last Update Posted: May 17, 2023
• Last Verified: May 2023

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; Pridopidine; Prilenia Therapeutics

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