HEALEY ALS Platform Trial - Master Protocol

Phase 2

Active, not recruiting

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: ABBV-CLS-7262; Drug: DNL343

• 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.

Study Timeline

• Study First Submitted: 2020-03-03
• Study First Submitted QC: 2020-03-04
• Study First Posted: 2020-03-05
• Study Start: 2020-07-14
• Status Verified: 2024-06
• Last Update Submitted: 2024-12-26
• Last Update Posted: 2024-12-30
• Primary Completion: 2025-07
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1500

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.

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