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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 : August 31, 2020
Sponsor:
Collaborator:
Massachusetts General Hospital
Information provided by (Responsible Party):
Merit E. Cudkowicz, MD, Massachusetts General Hospital

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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Zilucoplan Drug: Verdiperstat Drug: CNM-Au8 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.

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

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 480 participants
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
Official Title: HEALEY ALS Platform Trial
Actual Study Start Date : July 14, 2020
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : September 2021


Arm Intervention/treatment
Experimental: Regimen A - Zilucoplan
Participants are randomized to receive either active zilucoplan or matching placebo.
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


Experimental: Regimen B - Verdiperstat
Participants are randomized to receive either active verdiperstat or matching placebo.
Drug: Verdiperstat

Drug: Verdiperstat

Administration: Oral

Dose: 600mg twice daily


Experimental: Regimen C - CNM-Au8
Participants are randomized to receive either active CNM-Au8 or matching placebo.
Drug: CNM-Au8

Drug: CNM-Au8

Administration: Oral

Dose: 30 mg or 60 mg daily





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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04297683


Contacts
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Contact: HEALEY Center for ALS at Massachusetts General Hospital 833-425-8257 (HALT ALS) healeyalsplatform@mgh.harvard.edu

Locations
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Sponsors and Collaborators
Merit E. Cudkowicz, MD
Massachusetts General Hospital
Investigators
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Principal Investigator: Merit Cudkowicz, MD Massachusetts General Hospital
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Responsible Party: Merit E. Cudkowicz, MD, Chief, Neurology Department, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04297683    
Other Study ID Numbers: 2019P003518
First Posted: March 5, 2020    Key Record Dates
Last Update Posted: August 31, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Master Protocol
Lou Gehrig's Disease
Additional relevant MeSH terms:
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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