HEALEY ALS Platform Trial - Master Protocol

• ClinicalTrials.gov Identifier: NCT04297683
• Recruitment Status: Active, not recruiting
• First Posted: March 5, 2020
• Last Update Posted: May 14, 2024
• Sponsor: Merit E. Cudkowicz, MD
• Collaborator: Massachusetts General Hospital
• Information provided by (Responsible Party): Merit E. Cudkowicz, MD, Massachusetts General Hospital

Tracking Information

• First Submitted Date: March 3, 2020
• First Posted Date: March 5, 2020
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: July 14, 2020
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 17, 2020)

Disease Progression [ Time Frame: 24 Weeks ]

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.

Original Primary Outcome Measures (submitted: March 4, 2020)

Disease Progression [ Time Frame: 24 Weeks ]

Change in disease severity over time as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).

Current Secondary Outcome Measures (submitted: March 4, 2020)

• Respiratory Function [ Time Frame: 24 Weeks ]
  Change in respiratory function over time as measured by Slow Vital Capacity (SVC).
• Muscle Strength [ Time Frame: 24 Weeks ]
  Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD).
• Survival [ Time Frame: 24 Weeks ]
  Comparison of rate of occurrence between groups.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: HEALEY ALS Platform Trial - Master Protocol
• Official Title: HEALEY ALS Platform Trial
• 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 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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

As new investigational products become available, additional regimens will be added to the HEALEY ALS Platform Trial.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Amyotrophic Lateral Sclerosis

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

• Drug: Verdiperstat

  Drug: Verdiperstat

  Administration: Oral

  Dose: 600mg twice daily

• Drug: CNM-Au8

  Drug: CNM-Au8

  Administration: Oral

  Dose: 30 mg or 60 mg daily

• Drug: Pridopidine

  Drug: Pridopidine

  Administration: Oral

  Dose: 45mg twice daily

• Drug: SLS-005 Trehalose

  Drug: SLS-005 Trehalose

  Administration: Infusion

  Dose: 0.75 g/kg weekly

• Drug: ABBV-CLS-7262

  Drug: ABBV-CLS-7162

  Administration: Oral

  Dose: Dose 1 or Dose 2

• Drug: DNL343

  Drug: DNL343

  Administration: Oral

  Dose: Once per day

Study Arms

• Experimental: Regimen A - Zilucoplan
  Participants are randomized to receive either active zilucoplan or matching placebo.
  Intervention: Drug: Zilucoplan
• Experimental: Regimen B - Verdiperstat
  Participants are randomized to receive either active verdiperstat or matching placebo.
  Intervention: Drug: Verdiperstat
• Experimental: Regimen C - CNM-Au8
  Participants are randomized to receive either active CNM-Au8 or matching placebo.
  Intervention: Drug: CNM-Au8
• Experimental: Regimen D - Pridopidine
  Participants are randomized to receive either active Pridopidine or matching placebo.
  Intervention: Drug: Pridopidine
• Experimental: Regimen E - SLS-005 Trehalose
  Participants are randomized to receive either active SLS-005 Trehalose or matching placebo.
  Intervention: Drug: SLS-005 Trehalose
• Experimental: Regimen F- ABBV-CLS-7262
  Participants are randomized to receive either active ABBV-CLS-7262 or matching placebo.
  Intervention: Drug: ABBV-CLS-7262
• Experimental: Regimen G - DNL343
  Participants are randomized to receive either active DNL343 or matching placebo.
  Intervention: Drug: DNL343

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 14, 2023): 1500
• Original Estimated Enrollment (submitted: March 4, 2020): 480
• Estimated Study Completion Date: April 2026
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

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 ≤ 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04297683
• Other Study ID Numbers: 2019P003518
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Merit E. Cudkowicz, MD, Massachusetts General Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Merit E. Cudkowicz, MD
• Original Study Sponsor: Same as current
• Collaborators: Massachusetts General Hospital

Investigators

• Principal Investigator: Merit Cudkowicz, MD; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: May 2024