Clinical trial NCT04297683: HEALEY ALS Platform Trial - Master Protocol
Official title: HEALEY ALS Platform Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Placebo-Controlled
Double-Blind
Master Protocol
Lou Gehrig's Disease
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
First posted: 2020-03-05
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: As new investigational products become available, additional regimens will be added to the HEALEY ALS Platform Trial.
Primary purpose: TREATMENT

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.

Eligibility 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 ≤ 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.

Primary outcomes:
measure: Disease Progression
timeFrame: 36 Weeks
Secondary outcomes:
measure: Respiratory Function
timeFrame: 36 Weeks
measure: Survival
timeFrame: 36 Weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Health
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: San Francisco
country: United States
facility: Forbes Norris MDA/ALS Research Center, California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Britain
country: United States
facility: Hospital for Special Care
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Davie
country: United States
facility: Nova Southeastern University
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Health System
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: North Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health/Corewell Health
state: Michigan
city: Duluth
country: United States
facility: Essentia Health
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical School
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri Health Care
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lincoln
country: United States
facility: Neurology Associates, P.C./Somnos Clinical Research
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Las Vegas Clinic
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Health Science
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Providence Brain and Spine Institute ALS Center
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Weinberg ALS Center, Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Penn
state: Pennsylvania
city: Philadelphia
country: United States
facility: Lewis Katz School of Medicine at Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburg Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Neurology
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: San Antonio
country: United States
facility: UTHSCSA
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Henrico
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Massachusetts General Hospital
name: Merit Cudkowicz, MD
role: PRINCIPAL_INVESTIGATOR
References: