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HEALEY ALS Platform Trial - Master Protocol

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ClinicalTrials.gov Identifier: NCT04297683
Recruitment Status : Recruiting
First Posted : March 5, 2020
Last Update Posted : December 29, 2020
Sponsor:
Collaborator:
Massachusetts General Hospital
Information provided by (Responsible Party):
Merit E. Cudkowicz, MD, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE March 3, 2020
First Posted Date  ICMJE March 5, 2020
Last Update Posted Date December 29, 2020
Actual Study Start Date  ICMJE July 14, 2020
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 4, 2020)
Disease Progression [ Time Frame: 24 Weeks ]
Change in disease severity over time as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2020)
  • Respiratory Function [ Time Frame: 24 Weeks ]
    Change in respiratory function over time as measured by Slow Vital Capacity (SVC).
  • Muscle Strength [ Time Frame: 24 Weeks ]
    Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD).
  • Survival [ Time Frame: 24 Weeks ]
    Comparison of rate of occurrence between groups.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE HEALEY ALS Platform Trial - Master Protocol
Official Title  ICMJE HEALEY ALS Platform Trial
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.
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.

In this trial, multiple investigational products for ALS will be tested simultaneously or sequentially. Each investigational product will be tested in a regimen. Each regimen consists of a placebo-controlled trial, meaning that the active investigational product and matching placebo will be tested in each regimen.

The additional details that govern the testing of each investigational product will be summarized in separate regimen-specific appendices (RSAs). Each regimen will have a separate ClinicalTrials.gov posting, which will include specific information about the regimen. All regimen-specific outcome measures will be detailed in each regimen posting.

Participants will have an equal chance to be randomized to all regimens that are active at the time of screening. Once randomized to a regimen, participants will be randomized in a 3:1 ratio to either study drug or placebo.

The following regimens are active in the trial:

Regimen A - Zilucoplan Regimen B - Verdiperstat Regimen C - CNM-Au8 Regimen D - Priodopidine

New regimens will be continuously added as new investigational products become available. The HEALEY ALS Platform Trial will enroll additional participants as each new regimen is available.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
As new investigational products become available, additional regimens will be added to the HEALEY ALS Platform Trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • Drug: Zilucoplan

    Drug: Zilucoplan

    Administration: Subcutaneous injection

    Dose: Minimum of .0.22 mg/kg daily to a maximum dose of 0.42 mg/kg daily, dependent on weight

  • Drug: Verdiperstat

    Drug: Verdiperstat

    Administration: Oral

    Dose: 600mg twice daily

  • Drug: CNM-Au8

    Drug: CNM-Au8

    Administration: Oral

    Dose: 30 mg or 60 mg daily

  • Drug: Pridopidine

    Drug: Pridopidine

    Administration: Oral

    Dose: 45mg twice daily

Study Arms  ICMJE
  • Experimental: Regimen A - Zilucoplan
    Participants are randomized to receive either active zilucoplan or matching placebo.
    Intervention: Drug: Zilucoplan
  • Experimental: Regimen B - Verdiperstat
    Participants are randomized to receive either active verdiperstat or matching placebo.
    Intervention: Drug: Verdiperstat
  • Experimental: Regimen C - CNM-Au8
    Participants are randomized to receive either active CNM-Au8 or matching placebo.
    Intervention: Drug: CNM-Au8
  • Experimental: Regimen D - Pridopidine
    Participants are randomized to receive either active Pridopidine or matching placebo.
    Intervention: Drug: Pridopidine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 25, 2020)
640
Original Estimated Enrollment  ICMJE
 (submitted: March 4, 2020)
480
Estimated Study Completion Date  ICMJE November 2022
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Sporadic or familial ALS diagnosed as clinically possible, probable, lab-supported probable, or definite ALS defined by revised El Escorial criteria.
  2. Age 18 years or older.
  3. Capable of providing informed consent and complying with study procedures, in the SI's opinion.
  4. Time since onset of weakness due to ALS ≤ 36 months at the time of the Master Protocol Screening Visit.
  5. Vital Capacity ≥ 50% of predicted capacity for age, height, and sex at the time of the Master Protocol Screening Visit measured by Slow Vital Capacity (SVC), or, if required due to pandemic-related restrictions, Forced Vital Capacity (FVC).
  6. Participants must either not take riluzole or be on a stable dose of riluzole for ≥ 30 days prior to the Master Protocol Screening Visit. Riluzole-naïve participants are permitted in the study.
  7. Participants must either not take edaravone or have completed at least one cycle of edaravone prior to the Master Protocol Screening Visit. Edaravone-naïve participants are permitted in the study.
  8. Participants must have the ability to swallow pills and liquids at the time of the Master Protocol Screening Visit and, in the SI's opinion, have the ability to swallow for the duration of the study.
  9. Geographically accessible to the site.

Exclusion Criteria:

  1. Clinically significant unstable medical condition (other than ALS) that would pose a risk to the participant, according to SI's judgment (e.g., cardiovascular instability, systemic infection, untreated thyroid dysfunction, or clinically significant laboratory abnormality or EKG changes).

    Lab abnormalities include, but are not limited to: Hemoglobin < 10 g/dL, White Blood Cells < 3.0 x 103/mm3, Neutrophils, Absolute ≤ 1000/mm3, Eosinophilia (absolute eosinophil count of ≥ 500 eosinophils per microliter), low platelet counts (< 150 x 109 per liter), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal (ULN), eGFR < 30 mL/min/1.73m2, thyroid-stimulating hormone (TSH) levels >10 mIU/L or <0.01 mIU/L.

  2. Presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that would impair ability of the participant to provide informed consent, in the SI's opinion.
  3. Active cancer or history of cancer, except for the following: basal cell carcinoma or successfully treated squamous cell carcinoma of the skin, cervical carcinoma in situ, prostatic carcinoma in situ, or other malignancies curatively treated and with no evidence of disease recurrence for at least 3 years.
  4. Use of investigational treatments for ALS (off-label use or active participation in a clinical trial) within 5 half-lives (if known) or 30 days (whichever is longer) prior to the Master Protocol Screening Visit.
  5. Exposure at any time to any gene therapies under investigation for the treatment of ALS (off-label use or investigational).
  6. If female, breastfeeding, known to be pregnant, planning to become pregnant during the study, or of child-bearing potential and unwilling to use effective contraception for the duration of the trial and for 3 months, or longer as specified in each RSA, after discontinuing study treatment.
  7. If male of reproductive capacity, unwilling to use effective contraception for the duration of the trial and for 3 months, or longer as specified in each RSA, after discontinuing study treatment.
  8. Anything that would place the participant at increased risk or preclude the participant's full compliance with or completion of the study, in the SI's opinion.
  9. If a participant is being re-screened, the disqualifying condition has not been resolved, or the mandatory wash-out duration has not occurred.
  10. For those participating in the optional CSF collection, contraindication to undergoing a lumbar puncture (LP) in the SI's opinion. Participants undergoing the LP must not be currently taking anticoagulation medications such as warfarin that would be a contraindication to LP; aspirin and non-steroidal anti-inflammatories are allowed.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: HEALEY Center for ALS at Massachusetts General Hospital 833-425-8257 (HALT ALS) healeyalsplatform@mgh.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04297683
Other Study ID Numbers  ICMJE 2019P003518
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Merit E. Cudkowicz, MD, Massachusetts General Hospital
Study Sponsor  ICMJE Merit E. Cudkowicz, MD
Collaborators  ICMJE Massachusetts General Hospital
Investigators  ICMJE
Principal Investigator: Merit Cudkowicz, MD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP