HEALEY ALS Platform Trial - Master Protocol

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

HEALEY ALS Platform Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04297683
• Other study ID #: 2019P003518
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: July 14, 2020
• Est. completion date: April 2026

Study information

• Verified date: May 2024
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 A - Zilucoplan Regimen B - Verdiperstat Regimen C - CNM-Au8 Regimen D - Priodopidine Regimen E - SLS-005 Trehalose 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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 1500
• Est. completion date: April 2026
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 = 36 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.

10. Participants must either not take Relyvrio/ Albrioza or have started Relyvrio/ Albrioza = 30 days prior to the Master Protocol Screening Visit.

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, untreated thyroid dysfunction), 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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

Drug:
• Zilucoplan
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
• Verdiperstat
Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily
• CNM-Au8
Drug: CNM-Au8 Administration: Oral Dose: 30 mg or 60 mg daily
• Pridopidine
Drug: Pridopidine Administration: Oral Dose: 45mg twice daily
• SLS-005 Trehalose
Drug: SLS-005 Trehalose Administration: Infusion Dose: 0.75 g/kg weekly
• ABBV-CLS-7262
Drug: ABBV-CLS-7162 Administration: Oral Dose: Dose 1 or Dose 2
• DNL343
Drug: DNL343 Administration: Oral Dose: Once per day

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Merit E. Cudkowicz, MD	Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Progression	Change in disease severity over time as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Each type of function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Patients with higher scores have more physical function.	24 Weeks
Secondary	Respiratory Function	Change in respiratory function over time as measured by Slow Vital Capacity (SVC).	24 Weeks
Secondary	Muscle Strength	Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD).	24 Weeks
Secondary	Survival	Comparison of rate of occurrence between groups.	24 Weeks