HEALEY ALS Platform Trial - Master Protocol
Amyotrophic Lateral Sclerosis
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring ALS, Placebo-Controlled, Double-Blind, Master Protocol, Lou Gehrig's Disease
Eligibility Criteria
Inclusion Criteria:
- 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 ≤ 36 months at the time of the Master Protocol Screening Visit.
- Vital Capacity ≥ 50% of predicted capacity for age, height, and sex 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).
- Participants must either not take riluzole or be on a stable dose of riluzole for ≥ 30 days prior to the Master Protocol Screening Visit. Riluzole-naïve participants are permitted in the study.
- Participants must either not take edaravone or have completed at least one cycle of edaravone prior to the Master Protocol Screening Visit. Edaravone-naïve participants are permitted in the study.
- 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.
Exclusion Criteria:
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).
Lab abnormalities include, but are not limited to: Hemoglobin < 10 g/dL, White Blood Cells < 3.0 x 103/mm3, Neutrophils, Absolute ≤ 1000/mm3, Eosinophilia (absolute eosinophil count of ≥ 500 eosinophils per microliter), low platelet counts (< 150 x 109 per liter), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal (ULN), eGFR < 30 mL/min/1.73m2, thyroid-stimulating hormone (TSH) levels >10 mIU/L or <0.01 mIU/L.
- 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 longer 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 longer 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.
- For those participating in the optional CSF collection, contraindication to undergoing a lumbar puncture (LP) in the SI's opinion. Participants undergoing the LP must not be currently taking anticoagulation medications such as warfarin that would be a contraindication to LP; aspirin and non-steroidal anti-inflammatories are allowed.
Sites / Locations
- Barrow Neurological InstituteRecruiting
- Loma Linda University HealthRecruiting
- University of Southern CaliforniaRecruiting
- Cedars-Sinai Medical CenterRecruiting
- University of California, IrvineRecruiting
- Forbes Norris MDA/ALS Research Center, California Pacific Medical CenterRecruiting
- University of California, San FranciscoRecruiting
- University of ColoradoRecruiting
- Hospital for Special CareRecruiting
- Georgetown UniversityRecruiting
- George Washington UniversityRecruiting
- Nova Southeastern UniversityRecruiting
- Phil Smith Neuroscience Institute at Holy Cross HospitalRecruiting
- University of FloridaRecruiting
- Mayo Clinic Florida
- University of MiamiRecruiting
- University of South FloridaRecruiting
- Emory University
- Augusta UniversityRecruiting
- Saint Alphonsus Regional Medical CenterRecruiting
- Northwestern UniversityRecruiting
- University of ChicagoRecruiting
- Indiana University Health
- University of Iowa Hospitals and ClinicsRecruiting
- University of Kansas Medical CenterRecruiting
- University of KentuckyRecruiting
- Ochsner Health System
- University of MarylandRecruiting
- Johns Hopkins UniversityRecruiting
- Massachusetts General HospitalRecruiting
- Beth Israel Deaconess Medical CenterRecruiting
- University of Massachusetts Medical SchoolRecruiting
- University of MichiganRecruiting
- Henry Ford Health SystemRecruiting
- Spectrum Health
- Essentia HealthRecruiting
- University of Minnesota/Twin Cities ALS Research ConsortiumRecruiting
- Mayo Clinic - RochesterRecruiting
- University of Missouri Health Care
- Saint Louis University
- Washington University School of MedicineRecruiting
- Neurology Associates, P.C./Somnos Clinical Research
- University of Nebraska Medical CenterRecruiting
- Las Vegas Clinic
- Dartmouth-Hitchcock Medical CenterRecruiting
- Columbia University
- SUNY UpstateRecruiting
- Duke UniversityRecruiting
- Wake Forest Health ScienceRecruiting
- University of CincinnatiRecruiting
- Cleveland ClinicRecruiting
- The Ohio State UniversityRecruiting
- Providence Brain and Spine Institute ALS CenterRecruiting
- Lehigh Valley Health NetworkRecruiting
- Penn State HersheyRecruiting
- Jefferson Weinberg ALS Center, Thomas Jefferson UniversityRecruiting
- University of PennRecruiting
- Lewis Katz School of Medicine at Temple UniversityRecruiting
- University of Pittsburg Medical CenterRecruiting
- Vanderbilt University Medical CenterRecruiting
- Texas NeurologyRecruiting
- Houston MethodistRecruiting
- UTHSCSARecruiting
- University of UtahRecruiting
- University of VirginiaRecruiting
- Swedish Medical CenterRecruiting
- University of WashingtonRecruiting
- Medical College of WisconsinRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Regimen A - Zilucoplan
Regimen B - Verdiperstat
Regimen C - CNM-Au8
Regimen D - Pridopidine
Regimen E - SLS-005 Trehalose
Regimen F- ABBV-CLS-7262
Regimen G - DNL343
Participants are randomized to receive either active zilucoplan or matching placebo.
Participants are randomized to receive either active verdiperstat or matching placebo.
Participants are randomized to receive either active CNM-Au8 or matching placebo.
Participants are randomized to receive either active Pridopidine or matching placebo.
Participants are randomized to receive either active SLS-005 Trehalose or matching placebo.
Participants are randomized to receive either active ABBV-CLS-7262 or matching placebo.
Participants are randomized to receive either active DNL343 or matching placebo.