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| Name | Class |
|---|---|
| Biohaven Pharmaceuticals, Inc. | INDUSTRY |
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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.
Regimen B will evaluate the safety and efficacy of a single study drug, verdiperstat, in participants with ALS.
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. The HEALEY ALS Platform Trial Master Protocol is registered as NCT04297683.
Once a participant enrolls into the Master Protocol and meets all eligibility criteria, the participant will be eligible to be randomized into any currently enrolling regimen. All participants will have an equal chance of being randomized to any currently enrolling regimen.
If a participant is randomized to Regimen B - Verdiperstat, the participant will complete a screening visit to assess additional Regimen B eligibility criteria. Once Regimen B eligibility criteria are confirmed, participants will complete a baseline assessment and be randomized in a 3:1 ratio to either active Verdiperstat or matching placebo.
Regimen B will enroll by invitation as participants may not choose to enroll in Regimen B. Participants must first enroll into the Master Protocol and be eligible to participate in the Master Protocol before being able to be randomly assigned to Regimen B.
For a list of enrolling sites, please see the HEALEY ALS Platform Trial Master Protocol under NCT04297683.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Verdiperstat | Experimental | Verdiperstat is administered twice daily p.o. for 24 weeks. |
|
| Matching Placebo | Placebo Comparator | Matching placebo is administered twice daily p.o. for 24 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Matching Placebo | Drug | Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Disease Progression as Assessed by the ALSFRS-R-Slope | Change in disease severity as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) total score using a Bayesian repeated measures model that accounts for loss to follow-up due to mortality. Each of 12 questions assessing distinct functional ability 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. | Baseline to 24 Weeks |
| Mortality Even Rate | Mortality is defined as death or death equivalent. A participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row. The rate of mortality was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times. | Baseline to 24 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Respiratory Function | Change in respiratory function over time as measured by Slow Vital Capacity (SVC). | Baseline to 24 Weeks |
| Muscle Strength | Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD). |
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Inclusion Criteria:
Exclusion Criteria:
The following exclusion criteria are in addition to the exclusion criteria specified in the Master Protocol (NCT NCT04297683).
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| Name | Affiliation | Role |
|---|---|---|
| Merit Cudkowicz, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Healey Center for ALS at Mass General | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40067754 | Derived | Writing Committee for the HEALEY ALS Platform Trial; Andrews J, Paganoni S, Macklin EA, Chibnik LB, Quintana M, Saville BR, Detry MA, Vestrucci M, Marion J, McGlothlin A, Young E, Chase M, Pothier L, Harkey B, Yu H, Sherman A, Shefner J, Hall M, Kittle G, Connolly MR, Berry JD, D'Agostino D, Tustison E, Giacomelli E, Scirocco E, Alameda G, Locatelli E, Ho D, Quick A, Heitzman D, Ajroud-Driss S, Appel SH, Shroff S, Katz J, Felice K, Maragakis NJ, Simmons Z, Goutman SA, Olney N, Miller T, Fernandes JA, Ilieva H, Jawdat O, Weiss MD, Foster L, Vu T, Ladha S, Owegi MA, Newman DS, Arcila-Londono X, Jackson CE, Swenson A, Heiman-Patterson T, Caress J, Fee D, Peltier A, Lewis R, Rosenfeld J, Walk D, Johnson K, Elliott M, Kasarskis EJ, Rutkove S, McIlduff CE, Bedlack R, Elman L, Goyal NA, Rezania K, Twydell P, Benatar M, Glass J, Cohen JA, Jones V, Zilliox L, Wymer JP, Beydoun SR, Shah J, Pattee GL, Martinez-Thompson J, Nayar S, Granit V, Donohue M, Grossman K, Campbell DJ, Qureshi IA, Cudkowicz ME, Babu S. Verdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial. JAMA Neurol. 2025 Apr;82(4):333-343. doi: 10.1001/jamaneurol.2024.5249. Epub 2025 Feb 17. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Verdiperstat | Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily |
| FG001 | Matching Placebo | Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Baseline Analysis Population includes only placebo participants from the Regimen B Efficacy Regimen Only (ERO) sample; shared placebo participants from other regimens are not included in the Baseline Analysis Population.
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| ID | Title | Description |
|---|---|---|
| BG000 | Verdiperstat | Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily |
| BG001 | Matching Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Disease Progression as Assessed by the ALSFRS-R-Slope | Change in disease severity as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) total score using a Bayesian repeated measures model that accounts for loss to follow-up due to mortality. Each of 12 questions assessing distinct functional ability 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. | Outcome measure data was analyzed using the Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen A Zilucoplan (NCT04436497) and Regimen C CNM-Au8 (NCT04414345) contributed placebo participants into the shared placebo cohort used for analysis. | Posted | Mean | Standard Deviation | ALSFRS-R total score points per month | Baseline to 24 Weeks |
|
Up to 35 weeks after participant signed Master Protocol consent.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Verdiperstat | Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Healey Center for ALS Project Management | Healey Center for ALS at Massachusetts General Hospital | 833-425-8257 (HALT ALS) | healeyalsplatform@mgh.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 2, 2021 | Apr 5, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 22, 2022 | Apr 4, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
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| Verdiperstat | Drug | Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily |
|
| Baseline to 24 Weeks |
| Number of Participants That Experienced Death or Death Equivalent | The number of participants who died or met the criterion for a death equivalent from the date of their baseline visit to the end of the Week 24 visit window (generally 175 days after baseline). The death equivalent criterion is use of permanent assisted ventilation (PAV) for more than 22 hours per day for more than 7 days in a row. | 24 Weeks |
Matching placebo is administered twice daily p.o. for 24 weeks.
Matching Placebo: Drug: Matching Placebo
Administration: Oral
Dose: two tablets twice daily
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| El Escorial Diagnosis | Count of Participants | Participants |
|
| Time Since Symptom onset at Baseline | Mean | Standard Deviation | months |
|
| Delay in ALS Symptom Onset and Diagnosis | Mean | Standard Deviation | months |
|
| ALS Onset Location | Count of Participants | Participants |
|
| Baseline Edaravone Use | Count of Participants | Participants |
|
| Baseline Riluzole Use | Count of Participants | Participants |
|
| ALSFRS-R Total Score | The ALS Functional Rating Scare-Revised (ALSFRS-R) measures 12 aspects of physical function. Each of the 12 questions assessing distinct functional ability is scored from4(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. | Mean | Standard Deviation | scores on a scale |
|
| Change in ALSFRS-R prior to Baseline | The ALS Functional Rating Scare-Revised (ALSFRS-R) measures 12 aspects of physical function. Each of the 12 questions assessing distinct functional ability is scored from4(normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Baseline decline in ALSFRS-R was calculated as 48minus the ALSFRS-R total score at Baseline. The difference between 48 and ALSFRS-R total score at Baseline is divided by the number of months between onset of weakness due to ALS and the date of Baseline. A higher number indicates greater decline. | Mean | Standard Deviation | points per month |
|
| SVC | Number analyzed in row differs from overall number due to missing data. | Mean | Standard Deviation | Percent Predicted |
|
| Kings Stage | The King's ALS Clinical Staging System is a 4-level ordinal scale with the first three levels indicating the number (1, 2, or 3) of distinct central nervous system regions (bulbar, upper limb, and lower limb) with neuromuscular dysfunction. Level 4a indicates nutritional failure and level 4b indicates respiratory failure. Higher scores indicate a worse disease state. | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Serum Creatinine Concentration | Mean | Standard Deviation | mg/dL |
|
| Neurofilament Light (NfL) Protein in Serum | Number analyzed in row differs from overall number due to missing data. | Mean | Standard Deviation | ng/L |
|
Verdiperstat is administered twice daily p.o. for 24 weeks.
Verdiperstat: Drug: Verdiperstat
Administration: Oral
Dose: 600mg twice daily
| OG001 | Matching Placebo | Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily |
|
|
|
| Primary | Mortality Even Rate | Mortality is defined as death or death equivalent. A participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row. The rate of mortality was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times. | Outcome measure data was analyzed using the Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen A Zilucoplan (NCT04436497) and Regimen C CNM-Au8 (NCT04414345) contributed placebo participants into the shared placebo cohort used for analysis. | Posted | Mean | Standard Deviation | events per month | Baseline to 24 Weeks |
|
|
|
| Secondary | Respiratory Function | Change in respiratory function over time as measured by Slow Vital Capacity (SVC). | Outcome measure data was analyzed using the Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen A Zilucoplan (NCT04436497) and Regimen C CNM-Au8 (NCT04414345) contributed placebo participants into the shared placebo cohort used for analysis. | Posted | Least Squares Mean | Standard Error | percent change | Baseline to 24 Weeks |
|
|
|
|
| Secondary | Muscle Strength | Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD). | Outcome measure data was analyzed using the Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen A Zilucoplan (NCT04436497) and Regimen C CNM-Au8 (NCT04414345) contributed placebo participants into the shared placebo cohort used for analysis. | Posted | Least Squares Mean | Standard Error | percent change | Baseline to 24 Weeks |
|
|
|
|
| Secondary | Number of Participants That Experienced Death or Death Equivalent | The number of participants who died or met the criterion for a death equivalent from the date of their baseline visit to the end of the Week 24 visit window (generally 175 days after baseline). The death equivalent criterion is use of permanent assisted ventilation (PAV) for more than 22 hours per day for more than 7 days in a row. | Outcome measure data was analyzed using the Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen A Zilucoplan (NCT04436497) and Regimen C CNM-Au8 (NCT04414345) contributed placebo participants into the shared placebo cohort used for analysis. | Posted | Count of Participants | Participants | 24 Weeks |
|
|
|
|
| 6 |
| 126 |
| 20 |
| 126 |
| 114 |
| 126 |
| EG001 | Matching Placebo | Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily | 0 | 41 | 2 | 41 | 37 | 41 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Amyotrophic lateral sclerosis | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Aphasia | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Bacterial sepsis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| COVID-19 pneumonia | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Failure to thrive | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Sudden death | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
|
| Hepatic enzyme abnormal | Investigations | MedDRA 23.0 | Non-systematic Assessment |
|
| B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Non-systematic Assessment |
|
| Muscular weakness | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Neuromyopathy | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Tension headache | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dysarthria | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Blood thyroid stimulating hormone increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
|
| Urine odour abnormal | Renal and urinary disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
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| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Clinically Probable ALS - Laboratory Supported |
|
| Clinically Possible ALS |
|
| Generalized |
|
| Limb |
|
| Respiratory |
|
| 3 Regions with Neuromuscular Dysfunction |
|
| 4a/b Nutritional/Respiratory Failure |
|
| 4b Respiratory Failure |
|