HEALEY ALS Platform Trial - Regimen D Pridopidine

Phase 2

Completed

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: Matching Placebo; Drug: Pridopidine

• Registration Number: NCT04615923
• Lead Sponsor: Merit E. Cudkowicz, MD

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.

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 Timeline

• Study First Submitted: 2020-10-29
• Study First Submitted QC: 2020-10-29
• Study First Posted: 2020-11-04
• Study Start: 2020-12-18
• Primary Completion: 2022-07-14
• Study Completion: 2022-07-14
• Results First Submitted: 2023-06-30
• Status Verified: 2023-08
• Results First Submitted QC: 2023-08-12
• Last Update Submitted: 2023-08-12
• Results First Posted: 2023-08-23
• Last Update Posted: 2023-08-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 163

Inclusion Criteria

• No additional inclusion criteria beyond the inclusion criteria specified in the Master Protocol (NCT NCT04297683).

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Matching Placebo	Matching Placebo	Matching placebo is administered orally twice daily for 24 weeks.
Pridopidine	Pridopidine	Pridopidine is administered orally twice daily for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Disease Progression as Assessed by the ALSFRS-R Total Score	Baseline to 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.
Mortality Event 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
Change in Bulbar Function in Participants With Bulbar Dysfunction at Baseline	Baseline to 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.; 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.
Bulbar Function in All Randomized Participants	Baseline to 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.
Respiratory Function	Baseline to 24 Weeks	Change in respiratory function over time as measured by Slow Vital Capacity (SVC).
Bulbar Function in Participants With Rapid Pre-baseline Progression	Baseline to 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.; 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.
Time to Bulbar Decline	Baseline to 24 Weeks	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.
Muscle Strength	Baseline to 24 Weeks	Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD).
Number of Participants That Experienced Death or Death Equivalent	Baseline to 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 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.

Trial Locations

Locations (1)

Healey Center for ALS at Mass General; 🇺🇸 Boston, Massachusetts, United States