HEALEY ALS Platform Trial - Master Protocol
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Registration Number
- NCT04297683
- Lead Sponsor
- Merit E. Cudkowicz, MD
- 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 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1500
- 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.
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regimen F- ABBV-CLS-7262 ABBV-CLS-7262 Participants are randomized to receive either active ABBV-CLS-7262 or matching placebo. Regimen G - DNL343 DNL343 Participants are randomized to receive either active DNL343 or matching placebo.
- Primary Outcome Measures
Name Time Method Disease Progression 36 Weeks Change in disease severity as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) total score and survival.
- Secondary Outcome Measures
Name Time Method Respiratory Function 36 Weeks Change in respiratory function over time as measured by Slow Vital Capacity (SVC).
Survival 36 Weeks Comparison of rate of occurrence between groups.
Trial Locations
- Locations (76)
Neurology Associates, P.C./Somnos Clinical Research
🇺🇸Lincoln, Nebraska, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
University of Pittsburg Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Washington
🇺🇸Seattle, Washington, United States
Indiana University Health
🇺🇸Indianapolis, Indiana, United States
Las Vegas Clinic
🇺🇸Las Vegas, Nevada, United States
Houston Methodist
🇺🇸Houston, Texas, United States
University of Minnesota Medical School
🇺🇸Minneapolis, Minnesota, United States
Duke University
🇺🇸Durham, North Carolina, United States
UTHSCSA
🇺🇸San Antonio, Texas, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
University of California, Irvine
🇺🇸Orange, California, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
University of Miami
🇺🇸Miami, Florida, United States
Forbes Norris MDA/ALS Research Center, California Pacific Medical Center
🇺🇸San Francisco, California, United States
Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
SUNY Upstate
🇺🇸Syracuse, New York, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Hospital for Special Care
🇺🇸New Britain, Connecticut, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Spectrum Health/Corewell Health
🇺🇸Grand Rapids, Michigan, United States
Nova Southeastern University
🇺🇸Davie, Florida, United States
Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
Saint Alphonsus Regional Medical Center
🇺🇸Boise, Idaho, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Lehigh Valley Health Network
🇺🇸Allentown, Pennsylvania, United States
Texas Neurology
🇺🇸Dallas, Texas, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Penn State Hershey
🇺🇸Hershey, Pennsylvania, United States
University of Penn
🇺🇸Philadelphia, Pennsylvania, United States
Virginia Commonwealth University
🇺🇸Henrico, Virginia, United States
University of Missouri Health Care
🇺🇸Columbia, Missouri, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
George Washington University
🇺🇸Washington, District of Columbia, United States
Augusta University
🇺🇸Augusta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Massachusetts Medical School
🇺🇸North Worcester, Massachusetts, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
University of South Florida
🇺🇸Tampa, Florida, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Wake Forest Health Science
🇺🇸Winston-Salem, North Carolina, United States
Providence Brain and Spine Institute ALS Center
🇺🇸Portland, Oregon, United States
Loma Linda University Health
🇺🇸Loma Linda, California, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Essentia Health
🇺🇸Duluth, Minnesota, United States
Columbia University
🇺🇸New York, New York, United States
Dent Neurologic Institute
🇺🇸Amherst, New York, United States
Atrium Health
🇺🇸Charlotte, North Carolina, United States
Lewis Katz School of Medicine at Temple University
🇺🇸Philadelphia, Pennsylvania, United States
Jefferson Weinberg ALS Center, Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Ochsner Health System
🇺🇸New Orleans, Louisiana, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
University of Kansas Medical Center
🇺🇸Fairway, Kansas, United States