HEALEY ALS Platform Trial - Master Protocol

Sponsor

Merit E. Cudkowicz, MD (Other)

Overall Status

Recruiting

CT.gov ID

NCT04297683

Collaborator

Massachusetts General Hospital (Other)

800

Enrollment

Locations

Arms

40.6

Anticipated Duration (Months)

12.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: Zilucoplan Drug: Verdiperstat Drug: CNM-Au8 Drug: Pridopidine Drug: SLS-005 Trehalose	Phase 2/Phase 3

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

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 Design

Study Type:

Interventional

Anticipated Enrollment :

800 participants

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.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

Official Title:

HEALEY ALS Platform Trial

Actual Study Start Date :

Jul 14, 2020

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Regimen A - Zilucoplan Participants are randomized to receive either active zilucoplan or matching placebo.	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
Experimental: Regimen B - Verdiperstat Participants are randomized to receive either active verdiperstat or matching placebo.	Drug: Verdiperstat Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily
Experimental: Regimen C - CNM-Au8 Participants are randomized to receive either active CNM-Au8 or matching placebo.	Drug: CNM-Au8 Drug: CNM-Au8 Administration: Oral Dose: 30 mg or 60 mg daily
Experimental: Regimen D - Pridopidine Participants are randomized to receive either active Pridopidine or matching placebo.	Drug: Pridopidine Drug: Pridopidine Administration: Oral Dose: 45mg twice daily
Experimental: Regimen E - SLS-005 Trehalose Participants are randomized to receive either active SLS-005 Trehalose or matching placebo.	Drug: SLS-005 Trehalose Drug: SLS-005 Trehalose Administration: Infusion Dose: 0.75 g/kg weekly

Outcome Measures

Primary Outcome Measures

Disease Progression [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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barrow Neurological Institute	Phoenix	Arizona	United States	85013
2	Loma Linda University Health	Loma Linda	California	United States	92354
3	University of Southern California	Los Angeles	California	United States	90033
4	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
5	University of California, Irvine	Orange	California	United States	92868
6	Forbes Norris MDA/ALS Research Center, California Pacific Medical Cente	San Francisco	California	United States	94115
7	University of California, San Francisco	San Francisco	California	United States	94143
8	University of Colorado	Aurora	Colorado	United States	80045
9	Hospital for Special Care	New Britain	Connecticut	United States	06053
10	Georgetown University	Washington	District of Columbia	United States	20007
11	Phil Smith Neuroscience Institute at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
12	University of Florida	Gainesville	Florida	United States	32610
13	Mayo Clinic Florida	Jacksonville	Florida	United States	32224
14	University of Miami	Miami	Florida	United States	33136
15	University of South Florida	Tampa	Florida	United States	33612
16	Emory University	Atlanta	Georgia	United States	30322
17	Augusta University	Augusta	Georgia	United States	30912
18	Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83704
19	Northwestern University	Chicago	Illinois	United States	60611
20	University of Chicago	Chicago	Illinois	United States	60637
21	Indiana University Health	Indianapolis	Indiana	United States	46202
22	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
23	University of Kansas Medical Center	Fairway	Kansas	United States	66205
24	University of Kentucky	Lexington	Kentucky	United States	40536
25	Ochsner Health System	New Orleans	Louisiana	United States	70115
26	University of Maryland	Baltimore	Maryland	United States	21201
27	Johns Hopkins University	Baltimore	Maryland	United States	21205
28	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
29	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
30	University of Massachusetts Medical School	North Worcester	Massachusetts	United States	01655
31	University of Michigan	Ann Arbor	Michigan	United States	48109
32	Henry Ford Health System	Detroit	Michigan	United States	48202
33	Spectrum Health	Grand Rapids	Michigan	United States	49525
34	Essentia Health	Duluth	Minnesota	United States	55805
35	University of Minnesota/Twin Cities ALS Research Consortium	Minneapolis	Minnesota	United States	55455
36	Mayo Clinic - Rochester	Rochester	Minnesota	United States	55902
37	University of Missouri Health Care	Columbia	Missouri	United States	65212
38	Saint Louis University	Saint Louis	Missouri	United States	63104
39	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
40	Neurology Associates, P.C./Somnos Clinical Research	Lincoln	Nebraska	United States	68506
41	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
42	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
43	Columbia University	New York	New York	United States	10032
44	SUNY Upstate	Syracuse	New York	United States	13202
45	Duke University	Durham	North Carolina	United States	27702
46	Wake Forest Health Science	Winston-Salem	North Carolina	United States	27157
47	University of Cincinnati	Cincinnati	Ohio	United States	45219
48	The Ohio State University	Columbus	Ohio	United States	43221
49	Providence Brain and Spine Institute ALS Center	Portland	Oregon	United States	97213
50	Lehigh Valley Health Network	Allentown	Pennsylvania	United States	18103
51	Penn State Hershey	Hershey	Pennsylvania	United States	17033
52	Jefferson Weinberg ALS Center, Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
53	University of Penn	Philadelphia	Pennsylvania	United States	19107
54	Lewis Katz School of Medicine at Temple University	Philadelphia	Pennsylvania	United States	19140
55	University of Pittsburg Medical Center	Pittsburgh	Pennsylvania	United States	15232
56	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
57	Texas Neurology	Dallas	Texas	United States	75214
58	Houston Methodist	Houston	Texas	United States	77030
59	UTHSCSA	San Antonio	Texas	United States	78229
60	University of Utah	Salt Lake City	Utah	United States	84132
61	University of Virginia	Charlottesville	Virginia	United States	22908
62	Swedish Medical Center	Seattle	Washington	United States	98122
63	University of Washington	Seattle	Washington	United States	98195
64	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226