HEALEY ALS Platform Trial - Master Protocol

NCT04297683 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2019P003518
• Study Type: interventional
• Target: 1,500
• Locations: 1 country
• Sites: 78

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Disease Progression

  Change in disease severity as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) total score and survival.

  36 Weeks

Secondary Outcomes (2)

• Respiratory Function

  36 Weeks

• Survival

  36 Weeks

Study Arms (8)

Regimen A - Zilucoplan

EXPERIMENTAL

Participants are randomized to receive either active zilucoplan or matching placebo. NO LONGER RECRUITING; RESULTS REPORTED.

Drug: Zilucoplan

Regimen B - Verdiperstat

EXPERIMENTAL

Participants are randomized to receive either active verdiperstat or matching placebo. NO LONGER RECRUITING; RESULTS REPORTED.

Drug: Verdiperstat

Regimen C - CNM-Au8

EXPERIMENTAL

Participants are randomized to receive either active CNM-Au8 or matching placebo. NO LONGER RECRUITING; RESULTS REPORTED.

Drug: CNM-Au8

Regimen D - Pridopidine

EXPERIMENTAL

Participants are randomized to receive either active Pridopidine or matching placebo. NO LONGER RECRUITING; RESULTS REPORTED.

Drug: Pridopidine

Regimen E - SLS-005 Trehalose

EXPERIMENTAL

Participants are randomized to receive either active SLS-005 Trehalose or matching placebo. NO LONGER RECRUITING; RESULTS REPORTED.

Drug: SLS-005 Trehalose

Regimen F- ABBV-CLS-7262

EXPERIMENTAL

Participants are randomized to receive either active ABBV-CLS-7262 or matching placebo. NO LONGER RECRUITING; RESULTS REPORTED.

Drug: ABBV-CLS-7262

Regimen G - DNL343

EXPERIMENTAL

Participants are randomized to receive either active DNL343 or matching placebo. NO LONGER RECRUITING; RESULTS REPORTED.

Drug: DNL343

Regimen I - NUZ-001

EXPERIMENTAL

Participants are randomized to receive either active NUZ-001 or matching placebo.

Drug: NUZ-001

Interventions

Pridopidine DRUG

Drug: Pridopidine Administration: Oral Dose: 45mg twice daily

Regimen D - Pridopidine

Zilucoplan DRUG

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

Regimen A - Zilucoplan

Verdiperstat DRUG

Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily

Regimen B - Verdiperstat

CNM-Au8 DRUG

Drug: CNM-Au8 Administration: Oral Dose: 30 mg or 60 mg daily

Regimen C - CNM-Au8

ABBV-CLS-7262 DRUG

Drug: ABBV-CLS-7162 Administration: Oral Dose: Dose 1 or Dose 2

Regimen F- ABBV-CLS-7262

DNL343 DRUG

Drug: DNL343 Administration: Oral Dose: Once per day

Regimen G - DNL343

NUZ-001 DRUG

Drug: NUZ-001. Administration: Oral. Dose: Once per day.

Regimen I - NUZ-001

SLS-005 Trehalose DRUG

Drug: SLS-005 Trehalose Administration: Infusion Dose: 0.75 g/kg weekly

Regimen E - SLS-005 Trehalose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sporadic or familial ALS diagnosed as clinically possible, probable, lab-supported probable, or definite ALS defined by revised El Escorial criteria.
• Age 18 years or older.
• Capable of providing informed consent and complying with study procedures, in the SI's opinion.
• Time since onset of weakness due to ALS ≤ 24 months at the time of the Master Protocol Screening Visit.
• 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.
• Participants must either not take riluzole or be on a stable dose of riluzole for ≥ 30 days prior to the Master Protocol Screening Visit.
• 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.
• 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.
• Geographically accessible to the site.

You may not qualify if:

• 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.
• 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.
• 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.
• Exposure at any time to any gene therapies under investigation for the treatment of ALS (off-label use or investigational).
• 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.
• 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.
• 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.
• If a participant is being re-screened, the disqualifying condition has not been resolved, or the mandatory wash-out duration has not occurred.

Sponsors & Collaborators

• Merit E. Cudkowicz, MD: lead
• Massachusetts General Hospital: collaborator

Study Sites (78)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

RECRUITING

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259, United States

RECRUITING

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

RECRUITING

Loma Linda University Health

Loma Linda, California, 92354, United States

ACTIVE NOT RECRUITING

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

ACTIVE NOT RECRUITING

University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

ACTIVE NOT RECRUITING

University of California, Irvine

Orange, California, 92868, United States

ACTIVE NOT RECRUITING

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

San Francisco, California, 94115, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Hospital for Special Care

New Britain, Connecticut, 06053, United States

RECRUITING

Yale University

New Haven, Connecticut, 06519, United States

RECRUITING

Georgetown University

Washington D.C., District of Columbia, 20007, United States

RECRUITING

George Washington University

Washington D.C., District of Columbia, 20037, United States

RECRUITING

Nova Southeastern University

Davie, Florida, 33024, United States

RECRUITING

University of Florida

Gainesville, Florida, 32610, United States

ACTIVE NOT RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

ACTIVE NOT RECRUITING

University of Miami

Miami, Florida, 33136, United States

ACTIVE NOT RECRUITING

University of South Florida

Tampa, Florida, 33612, United States

RECRUITING

Augusta University

Augusta, Georgia, 30912, United States

ACTIVE NOT RECRUITING

Saint Alphonsus Regional Medical Center

Boise, Idaho, 83704, United States

ACTIVE NOT RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

ACTIVE NOT RECRUITING

Indiana University Health

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

University of Kansas Medical Center

Fairway, Kansas, 66205, United States

RECRUITING

University of Kentucky

Lexington, Kentucky, 40536, United States

ACTIVE NOT RECRUITING

Ochsner Health System

New Orleans, Louisiana, 70115, United States

ACTIVE NOT RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21205, United States

ACTIVE NOT RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

University of Massachusetts Medical School

North Worcester, Massachusetts, 01655, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

RECRUITING

Spectrum Health/Corewell Health

Grand Rapids, Michigan, 49525, United States

RECRUITING

Essentia Health

Duluth, Minnesota, 55805, United States

RECRUITING

University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, 55902, United States

RECRUITING

University of Missouri Health Care

Columbia, Missouri, 65212, United States

RECRUITING

Saint Louis University

St Louis, Missouri, 63104, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Neurology Associates, P.C./Somnos Clinical Research

Lincoln, Nebraska, 68506, United States

ACTIVE NOT RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

ACTIVE NOT RECRUITING

Dent Neurologic Institute

Amherst, New York, 14226, United States

RECRUITING

Mount Sinai

New York, New York, 10003, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

RECRUITING

SUNY Upstate

Syracuse, New York, 13202, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

ACTIVE NOT RECRUITING

Atrium Health

Charlotte, North Carolina, 28207, United States

RECRUITING

Duke University

Durham, North Carolina, 27702, United States

RECRUITING

Wake Forest Health Science

Winston-Salem, North Carolina, 27157, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45219, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43221, United States

RECRUITING

OhioHealth Research Institute

Westerville, Ohio, 43082, United States

RECRUITING

Providence Brain and Spine Institute ALS Center

Portland, Oregon, 97213, United States

ACTIVE NOT RECRUITING

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

RECRUITING

Penn State Hershey

Hershey, Pennsylvania, 17033, United States

RECRUITING

Jefferson Weinberg ALS Center, Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Lewis Katz School of Medicine at Temple University

Philadelphia, Pennsylvania, 19140, United States

RECRUITING

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Austin Neuromuscular Clinic

Austin, Texas, 78759, United States

RECRUITING

Texas Neurology

Dallas, Texas, 75214, United States

RECRUITING

Houston Methodist

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

UTHSCSA

San Antonio, Texas, 78229, United States

ACTIVE NOT RECRUITING

University of Utah

Salt Lake City, Utah, 84132, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22908, United States

RECRUITING

Virginia Commonwealth University

Henrico, Virginia, 23233, United States

ACTIVE NOT RECRUITING

Swedish Medical Center

Seattle, Washington, 98122, United States

RECRUITING

University of Washington

Seattle, Washington, 98195, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Related Publications (4)

• 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.

  PMID: 40067821 DERIVED

• 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.

  PMID: 40067755 DERIVED

• 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.

  PMID: 40067754 DERIVED

• 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.

  PMID: 39960672 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

zilucoplan; pridopidine

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Merit Cudkowicz, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

HEALEY Center for ALS at Massachusetts General Hospital

CONTACT

833-425-8257 (HALT ALS); healeyalsplatform@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Research participants, care providers, investigators and site staff (i.e. outcome assessors) will not be blinded to the regimen assignment, but they will be blinded to active product or matching placebo assignment and this blind will be maintained throughout the study. Quadruple masking remains consistent across all regimens which may start at different time points.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Neurology Department

Model Details: As new investigational products become available, additional regimens will be added to the HEALEY ALS Platform Trial.

Study Record Dates

• First Submitted: March 3, 2020
• First Posted: March 5, 2020
• Study Start: June 14, 2020
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (78)