HEALEY ALS Platform Trial - Master Protocol

NCT ID: NCT04297683

Last Updated: 2024-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

1500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-14

Study Completion Date

2026-04-30

Brief Summary

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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

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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 F - ABBV-CLS-7262 Regimen G - DNL343

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.

Conditions

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Amyotrophic Lateral Sclerosis

Keywords

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ALS Placebo-Controlled Double-Blind Master Protocol Lou Gehrig's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

As new investigational products become available, additional regimens will be added to the HEALEY ALS Platform Trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Regimen F- ABBV-CLS-7262

Participants are randomized to receive either active ABBV-CLS-7262 or matching placebo.

Group Type EXPERIMENTAL

ABBV-CLS-7262

Intervention Type DRUG

Drug: ABBV-CLS-7162

Administration: Oral

Dose: Dose 1 or Dose 2

Regimen G - DNL343

Participants are randomized to receive either active DNL343 or matching placebo.

Group Type EXPERIMENTAL

DNL343

Intervention Type DRUG

Drug: DNL343

Administration: Oral

Dose: Once per day

Interventions

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ABBV-CLS-7262

Drug: ABBV-CLS-7162

Administration: Oral

Dose: Dose 1 or Dose 2

Intervention Type DRUG

DNL343

Drug: DNL343

Administration: Oral

Dose: Once per day

Intervention Type DRUG

Eligibility Criteria

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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 ≤ 24 months at the time of the Master Protocol Screening Visit.
5. Vital Capacity ≥ 50% of predicted capacity 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) measured in person.
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.
7. Participants must either not take edaravone or have completed at least one cycle (typically 14 days) of edaravone prior to the Master Protocol Screening Visit.
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), or clinically significant laboratory abnormality or EKG changes. Clinically significant abnormal liver or kidney function is exclusionary. The following values \[alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 times the upper limit of normal (ULN) or estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min/1.73m2\] are exclusionary regardless of clinical symptoms.
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 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 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Massachusetts General Hospital

OTHER

Sponsor Role collaborator

Merit E. Cudkowicz, MD

OTHER

Sponsor Role lead

Responsible Party

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Merit E. Cudkowicz, MD

Chief, Neurology Department

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Merit Cudkowicz, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Loma Linda University Health

Loma Linda, California, United States

Site Status

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

University of California, Irvine

Orange, California, United States

Site Status

Forbes Norris MDA/ALS Research Center, California Pacific Medical Center

San Francisco, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

Hospital for Special Care

New Britain, Connecticut, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

George Washington University

Washington D.C., District of Columbia, United States

Site Status

Nova Southeastern University

Davie, Florida, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Mayo Clinic Florida

Jacksonville, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

Saint Alphonsus Regional Medical Center

Boise, Idaho, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Indiana University Health

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Fairway, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Ochsner Health System

New Orleans, Louisiana, United States

Site Status

University of Maryland

Baltimore, Maryland, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Massachusetts Medical School

North Worcester, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Spectrum Health/Corewell Health

Grand Rapids, Michigan, United States

Site Status

Essentia Health

Duluth, Minnesota, United States

Site Status

University of Minnesota Medical School

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status

University of Missouri Health Care

Columbia, Missouri, United States

Site Status

Saint Louis University

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Neurology Associates, P.C./Somnos Clinical Research

Lincoln, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Las Vegas Clinic

Las Vegas, Nevada, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Dent Neurologic Institute

Amherst, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Stony Brook University Hospital

Stony Brook, New York, United States

Site Status

SUNY Upstate

Syracuse, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Atrium Health

Charlotte, North Carolina, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Wake Forest Health Science

Winston-Salem, North Carolina, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Providence Brain and Spine Institute ALS Center

Portland, Oregon, United States

Site Status

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Site Status

Penn State Hershey

Hershey, Pennsylvania, United States

Site Status

Jefferson Weinberg ALS Center, Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

University of Penn

Philadelphia, Pennsylvania, United States

Site Status

Lewis Katz School of Medicine at Temple University

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Texas Neurology

Dallas, Texas, United States

Site Status

Houston Methodist

Houston, Texas, United States

Site Status

UTHSCSA

San Antonio, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Virginia Commonwealth University

Henrico, Virginia, United States

Site Status

Swedish Medical Center

Seattle, Washington, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Writing Committee for the HEALEY ALS Platform Trial; Berry JD, Maragakis NJ, Macklin EA, Chibnik LB, Quintana M, Saville BR, Detry MA, Vestrucci M, Marion J, McGlothlin A, Stommel EW, Chase M, Pothier L, Harkey BA, Yu H, Sherman A, Shefner J, Hall M, Kittle G, Babu S, Andrews J, D'Agostino D, Tustison E, Scirocco E, Giacomelli E, Alameda G, Locatelli E, Ho D, Quick A, Ajroud-Driss S, Katz J, Heitzman D, Appel SH, Shroff S, Felice KJ, Simmons Z, Miller T, Olney N, Weiss MD, Goutman SA, Fernandes JA Jr, Jawdat O, Owegi MA, Foster L, Vu T, Ilieva H, Newman DS, Arcila-Londono X, Jackson C, Ladha S, Heiman-Patterson T, Caress J, Swenson A, Peltier A, Lewis R, Fee D, Elliott M, Bedlack R, Kasarskis EJ, Elman L, Rosenfeld J, Walk D, McIlduff CE, Twydell P, Young E, Johnson K, Rezania K, Goyal NA, Cohen JA, Benatar M, Jones V, Glass J, Shah J, Beydoun SR, Wymer JP, Zilliox L, Nayar S, Pattee GL, Martinez-Thompson J, Rynders A, Evan J, Evan J, Hartford A, Sepassi M, Ho KS, Glanzman R, Greenberg B, Hotchkin MT, Paganoni S, Cudkowicz ME; HEALEY ALS Platform Trial Study Group. CNM-Au8 in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial. JAMA. 2025 Feb 17;333(13):1138-49. doi: 10.1001/jama.2024.27643. Online ahead of print.

Reference Type DERIVED
PMID: 40067821 (View on PubMed)

Writing Committee for the HEALEY ALS Platform Trial; Shefner JM, Oskarsson B, Macklin EA, Chibnik LB, Quintana M, Saville BR, Detry MA, Vestrucci M, Marion J, McGlothlin A, Heiman-Patterson T, Chase M, Pothier L, Harkey BA, Yu H, Sherman AV, Hall M, Kittle G, Berry JD, Babu S, Andrews J, D'Agostino D, Tustison E, Scirocco E, Giacomelli E, Alameda G, Locatelli E, Ho D, Quick A, Ajroud-Driss S, Katz J, Heitzman D, Appel SH, Shroff S, Felice K, Maragakis NJ, Simmons Z, Miller TM, Olney N, Weiss MD, Goutman SA, Fernandes JA, Jawdat O, Owegi MA, Foster LA, Vu T, Ilieva H, Newman DS, Arcila-Londono X, Jackson CE, Ladha S, Caress JB, Swenson A, Peltier A, Lewis RA, Fee D, Elliott M, Bedlack R, Kasarskis EJ, Elman L, Rosenfeld J, Walk D, McIlduff C, Twydell P, Young E, Johnson K, Rezania K, Goyal NA, Cohen JA, Benatar M, Jones V, Shah J, Beydoun SR, Wymer JP, Zilliox L, Nayar S, Pattee GL, Martinez-Thompson J, Leitner ML, Chen K, Goldberg YP, Cohen Y, Geva M, Hayden MR, Paganoni S, Cudkowicz ME; HEALEY ALS Platform Trial Study Group. Pridopidine in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial. JAMA. 2025 Feb 17;333(13):1128-37. doi: 10.1001/jama.2024.26429. Online ahead of print.

Reference Type DERIVED
PMID: 40067755 (View on PubMed)

Writing Committee for the HEALEY ALS Platform Trial; Andrews J, Paganoni S, Macklin EA, Chibnik LB, Quintana M, Saville BR, Detry MA, Vestrucci M, Marion J, McGlothlin A, Young E, Chase M, Pothier L, Harkey B, Yu H, Sherman A, Shefner J, Hall M, Kittle G, Connolly MR, Berry JD, D'Agostino D, Tustison E, Giacomelli E, Scirocco E, Alameda G, Locatelli E, Ho D, Quick A, Heitzman D, Ajroud-Driss S, Appel SH, Shroff S, Katz J, Felice K, Maragakis NJ, Simmons Z, Goutman SA, Olney N, Miller T, Fernandes JA, Ilieva H, Jawdat O, Weiss MD, Foster L, Vu T, Ladha S, Owegi MA, Newman DS, Arcila-Londono X, Jackson CE, Swenson A, Heiman-Patterson T, Caress J, Fee D, Peltier A, Lewis R, Rosenfeld J, Walk D, Johnson K, Elliott M, Kasarskis EJ, Rutkove S, McIlduff CE, Bedlack R, Elman L, Goyal NA, Rezania K, Twydell P, Benatar M, Glass J, Cohen JA, Jones V, Zilliox L, Wymer JP, Beydoun SR, Shah J, Pattee GL, Martinez-Thompson J, Nayar S, Granit V, Donohue M, Grossman K, Campbell DJ, Qureshi IA, Cudkowicz ME, Babu S. Verdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial. JAMA Neurol. 2025 Apr;82(4):333-343. doi: 10.1001/jamaneurol.2024.5249. Epub 2025 Feb 17.

Reference Type DERIVED
PMID: 40067754 (View on PubMed)

Paganoni S, Fournier CN, Macklin EA, Chibnik LB, Quintana M, Saville BR, Detry MA, Vestrucci M, Marion J, McGlothlin A, Ajroud-Driss S, Chase M, Pothier L, Harkey BA, Yu H, Sherman AV, Shefner JM, Hall M, Kittle G, Berry JD, Babu S, Andrews J, Dagostino D, Tustison E, Giacomelli E, Scirocco E, Alameda G, Locatelli E, Ho D, Quick A, Katz J, Heitzman D, Appel SH, Shroff S, Felice K, Maragakis NJ, Simmons Z, Miller TM, Olney N, Weiss MD, Goutman SA, Fernandes JA, Jawdat O, Owegi MA, Foster LA, Vu T, Ilieva H, Newman DS, Arcila-Londono X, Jackson CE, Ladha S, Heiman-Patterson T, Caress JB, Swenson A, Peltier A, Lewis R, Fee D, Elliott M, Bedlack R, Kasarskis EJ, Elman L, Rosenfeld J, Walk D, McIlduff C, Twydell P, Young E, Johnson K, Rezania K, Goyal NA, Cohen JA, Benatar M, Jones V, Glass J, Shah J, Beydoun SR, Wymer JP, Zilliox L, Nayar S, Pattee GL, Martinez-Thompson J, Harvey B, Patel S, Mahoney P, Duda PW, Cudkowicz ME; HEALEY ALS Platform Trial Study Group. Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Netw Open. 2025 Feb 3;8(2):e2459058. doi: 10.1001/jamanetworkopen.2024.59058.

Reference Type DERIVED
PMID: 39960672 (View on PubMed)

Other Identifiers

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2019P003518

Identifier Type: -

Identifier Source: org_study_id