Back to resultsHEALEY ALS Platform Trial - Regimen D Pridopidine
Primary Purpose
Amyotrophic Lateral Sclerosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pridopidine
Matching Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring ALS, Placebo-Controlled, Double-Blind, Regimen Specific Appendix, Lou Gehrig's Disease, Pridopidine, Prilenia Therapeutics
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 with a confirmed prolonged Fridericia-corrected QT (QTcF) interval (defined as a QTcF interval of >450 ms for men and >470 ms for women).
- 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.
- Participants with known history of long QT syndrome or a first degree relative with this condition.
- Participants using prohibited medications within the 4 weeks prior to the Regimen Specific Screening Visit, as detailed in section 5.9.
Participants using the following medications at the time of the Regimen Specific Screening Visit:
- Nuedexta - at a dosage higher than 20 mg dextromethorphan + 10 mg quinidine BID
- Citalopram - at a dosage higher than 20 mg/day
- Escitalopram - at a dosage higher than 10 mg/day
- Participants with a known allergy to any ingredient of the study intervention (pridopidine, silicified microcrystalline cellulose, and magnesium stearate).
Sites / Locations
- Healey Center for ALS at Mass General
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Pridopidine
Matching Placebo
Arm Description
Pridopidine is administered orally twice daily for 24 weeks.
Matching placebo is administered orally twice daily for 24 weeks.
Outcomes
Primary Outcome Measures
Disease Progression as Assessed by the ALSFRS-R Total Score
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
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
Change in Bulbar Function in Participants With Bulbar Dysfunction at Baseline
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
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
Change in respiratory function over time as measured by Slow Vital Capacity (SVC).
Bulbar Function in Participants With Rapid Pre-baseline Progression
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
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
Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD).
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 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.
Full Information
NCT ID
NCT04615923
First Posted
October 29, 2020
Last Updated
August 12, 2023
Sponsor
Merit E. Cudkowicz, MD
Collaborators
Prilenia Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT04615923
Brief Title
HEALEY ALS Platform Trial - Regimen D Pridopidine
Official Title
HEALEY ALS Platform Trial - Regimen D Pridopidine
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
December 18, 2020 (Actual)
Primary Completion Date
July 14, 2022 (Actual)
Study Completion Date
July 14, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Merit E. Cudkowicz, MD
Collaborators
Prilenia Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
ALS, Placebo-Controlled, Double-Blind, Regimen Specific Appendix, Lou Gehrig's Disease, Pridopidine, Prilenia Therapeutics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
163 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pridopidine
Arm Type
Experimental
Arm Description
Pridopidine is administered orally twice daily for 24 weeks.
Arm Title
Matching Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo is administered orally twice daily for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Pridopidine
Intervention Description
Administration: Oral
Dose: 45mg twice daily
Intervention Type
Drug
Intervention Name(s)
Matching Placebo
Intervention Description
Administration: Oral
Dose: one capsule twice daily
Primary Outcome Measure Information:
Title
Disease Progression as Assessed by the ALSFRS-R Total Score
Description
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.
Time Frame
Baseline to 24 Weeks
Title
Mortality Event Rate
Description
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.
Time Frame
Baseline to 24 Weeks
Secondary Outcome Measure Information:
Title
Change in Bulbar Function in Participants With Bulbar Dysfunction at Baseline
Description
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.
Time Frame
Baseline to 24 Weeks
Title
Bulbar Function in All Randomized Participants
Description
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.
Time Frame
Baseline to 24 Weeks
Title
Respiratory Function
Description
Change in respiratory function over time as measured by Slow Vital Capacity (SVC).
Time Frame
Baseline to 24 Weeks
Title
Bulbar Function in Participants With Rapid Pre-baseline Progression
Description
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 Frame
Baseline to 24 Weeks
Title
Time to Bulbar Decline
Description
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.
Time Frame
Baseline to 24 Weeks
Title
Muscle Strength
Description
Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD).
Time Frame
Baseline to 24 Weeks
Title
Number of Participants That Experienced Death or Death Equivalent
Description
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.
Time Frame
Baseline to 24 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 with a confirmed prolonged Fridericia-corrected QT (QTcF) interval (defined as a QTcF interval of >450 ms for men and >470 ms for women).
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.
Participants with known history of long QT syndrome or a first degree relative with this condition.
Participants using prohibited medications within the 4 weeks prior to the Regimen Specific Screening Visit, as detailed in section 5.9.
Participants using the following medications at the time of the Regimen Specific Screening Visit:
Nuedexta - at a dosage higher than 20 mg dextromethorphan + 10 mg quinidine BID
Citalopram - at a dosage higher than 20 mg/day
Escitalopram - at a dosage higher than 10 mg/day
Participants with a known allergy to any ingredient of the study intervention (pridopidine, silicified microcrystalline cellulose, and magnesium stearate).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Merit Cudkowicz, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Healey Center for ALS at Mass General
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
HEALEY ALS Platform Trial - Regimen D Pridopidine
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