Operational Development and Launch of an Adaptive Platform Trial in Amyotrophic Lateral Sclerosis: Processes and Learnings From the First Four Regimens of the HEALEY ALS Platform Trial

doi:10.1002/mus.28442

Operational Development and Launch of an Adaptive Platform Trial in Amyotrophic Lateral Sclerosis: Processes and Learnings From the First Four Regimens of the HEALEY ALS Platform Trial

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4 Scopus citations

Abstract

Introduction/Aims: Platform trials present several advantages over traditional interventional clinical trials. Here, we provide a detailed description of the operational framework of the HEALEY ALS Platform Trial. Methods: Platform-level procedures for regulatory oversight, safety, and site management were developed prior to trial launch. Central vendors and a single Institutional Review Board (sIRB) were used. An Investigational New Drug (IND) application was submitted for the master protocol, and each regimen was added as an amendment. Results: The HEALEY ALS Platform Trial was launched in 2020. Fifty-four geographically diverse sites from the Northeast ALS Consortium (NEALS), all highly experienced in ALS care and research, were selected. Three investigational products were selected to launch concurrently at the start of the trial as individual regimens. A fourth investigational product was selected and added to the trial after the initial launch. The Master Protocol and the first three regimens (Regimens A-C) were sIRB approved in 120 days. sIRB amendment for Regimen D was approved in 21 days. Enrollment for regimens A–C was completed in 15 months, whereas Regimen D was completed in 11 months from the start of enrollment. Results of all regimens were available within approximately 2 years from the initial trial launch. Discussion: The HEALEY ALS Platform Trial capitalized on the benefits of the platform approach, including an adaptable operational infrastructure, concurrent enrollment into four distinct regimens, and an accelerated start-up time for a new regimen added after initial trial launch.

Original language	English
Pages (from-to)	294-305
Number of pages	12
Journal	Muscle and Nerve
Volume	72
Issue number	2
DOIs	https://doi.org/10.1002/mus.28442
State	Published - Aug 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.

Funding

Funding: This work was supported by philanthropic gifts to the Sean M. Healey and AMG Center for ALS and partially supported by Tackle ALS, ALS Finding a Cure, The ALS Association, ALS ONE, The Arthur M. Blank Family Foundation and the Muscular Dystrophy Association. UCB, Biohaven Pharmaceuticals, Inc, Clene Nanomedicine, and Prilenia Therapeutics provided investigational product and partially supported their individual regimen. This investigation was supported by philanthropic gifts to the Sean M. Healey and AMG Center for ALS and partially supported by Tackle ALS, ALS Finding a Cure, The ALS Association, ALS ONE, The Arthur M. Blank Family Foundation, and the Muscular Dystrophy Association. UCB, Biohaven Pharmaceuticals Inc., Clene Nanomedicine, and Prilenia Therapeutics provided investigational product and partially supported their individual regimen. We acknowledge the altruism of the participants and their families and contributions of the HEALEY ALS Platform Trial research and support staff at each of the participating sites for their contributions to this study. We are grateful for the formative input we received from all members of the HEALEY ALS Platform Trial Patient Advisory Committee and the Recruitment and Retention Committee, past and present. Additionally, we sincerely appreciate Raina Chrobak, MS, for creating the dynamic YouTube Studio dashboard used to track webinar views, and the members of the Data and Safety Monitoring Board (DSMB) (Jason Connor, PhD; Borje Darpo, MD, PhD FESC; Karl Kieburtz, MD, MPH; Ruth Schneider, MD; and Andrew Siderowf, MD) for their oversight and guidance in ensuring the integrity and safety of the trial. Suma Babu has received research funding from, OrphAI therapeutics, Biogen, Denali Therapeutics, Novartis, Orion, Ionis, American Academy of Neurology, AANEM Foundation and Muscular Dystrophy Association. She has received other honoraria from Biogen, Medscape and MDA. James Berry reports consulting fees from Biogen, MT Pharma of America, MT Pharma Holdings of America, Janssen, ALexion, Regeneron, and Amylyx. He has received research support from Biogen, Clene Nanomedicine, MT Pharma of America, MT Pharma Holdings of America, Alexion, Amylyx, Rapa Therapeutics, Brainstorm Cell Therapeutics, MDA, ALSA, ALS Finding A Cure, ALS One, Tambourine, DoD, and NINDS. He has been a paid educational speaker for PeerView and Projects in Knowledge. Merit Cudkowicz reports research grants from Prilenia, Seelos, Calico, Denali, ITB, NIH, ALS Finding a Cure and ALS One and reports consulting fees from Pasithea, Transposon, Vector Y, Infectis, Roche, AB Science, Novartis, Regeneron, Quralis, ImmunityPharm and Coya. She is a board member of Praxis Precision Medicine. Sabrina Paganoni reports research grants from Amylyx Therapeutics, Revalesio, Eledon, Alector, UCB Pharma, Biohaven, Clene Nanomedicine, Prilenia Therapeutics, Seelos, Calico, Denali, NIH, DoD, the Muscular Dystrophy Association and reports consulting fees from Amylyx, Arrowhead, Biogen, BMS, Clene Nanomedicine, Cytokinetics, Eikonizo, J&J, Merck, PharmAust, Prilenia, and Sola. She has been a paid educational speaker for Medscape, PeerView, and i3Health. Jeremy Shefner reports research Funding from: NIH, AB Sciences; Acorda Therapeutics; Alector; Amylyx; Biogen; Cytokinetics Incorporated; Ionis; Mitsubishi Tanabe Pharma America; Quralis; PTC; Sanofi; Wave; Myolex, and personal compensation for consulting from: Amylyx [ALS]; Cytokinetics [ALS]; Denali [ALS]; GSK [ALS]; Mitsubishi Tanabe Pharma America [ALS]; Neurosense [ALS]; Orthogonal [ALS]; Pinteon [ALS]; RRD [ALS]; Acurastem [ALS], Revalasio [ALS]; Apellis [ALS]; Swanbio [ALD]; Novartis [ALS]; Sanofi [ALS]; Eikonizo [ALS]; Sarepta [Muscular Dystrophy]. No other authors have disclosures to report.

Funders
Data and Safety Monitoring Board
Novartis
Amylyx Therapeutics
AANEM Foundation
Roche Canada
Merck
ALS Association
Prilenia Therapeutics
NIH
AB Science
Biohaven Pharmaceuticals
Muscular Dystrophy Association
ALS ONE
American Academy of Neurology

Keywords

HEALEY ALS platform trial
adaptive platform trials
amyotrophic lateral sclerosis
clinical operations
motor neuron disease

ASJC Scopus subject areas

Physiology
Clinical Neurology
Cellular and Molecular Neuroscience
Physiology (medical)

Access to Document

10.1002/mus.28442

Cite this

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title = "Operational Development and Launch of an Adaptive Platform Trial in Amyotrophic Lateral Sclerosis: Processes and Learnings From the First Four Regimens of the HEALEY ALS Platform Trial",

abstract = "Introduction/Aims: Platform trials present several advantages over traditional interventional clinical trials. Here, we provide a detailed description of the operational framework of the HEALEY ALS Platform Trial. Methods: Platform-level procedures for regulatory oversight, safety, and site management were developed prior to trial launch. Central vendors and a single Institutional Review Board (sIRB) were used. An Investigational New Drug (IND) application was submitted for the master protocol, and each regimen was added as an amendment. Results: The HEALEY ALS Platform Trial was launched in 2020. Fifty-four geographically diverse sites from the Northeast ALS Consortium (NEALS), all highly experienced in ALS care and research, were selected. Three investigational products were selected to launch concurrently at the start of the trial as individual regimens. A fourth investigational product was selected and added to the trial after the initial launch. The Master Protocol and the first three regimens (Regimens A-C) were sIRB approved in 120 days. sIRB amendment for Regimen D was approved in 21 days. Enrollment for regimens A–C was completed in 15 months, whereas Regimen D was completed in 11 months from the start of enrollment. Results of all regimens were available within approximately 2 years from the initial trial launch. Discussion: The HEALEY ALS Platform Trial capitalized on the benefits of the platform approach, including an adaptable operational infrastructure, concurrent enrollment into four distinct regimens, and an accelerated start-up time for a new regimen added after initial trial launch.",

keywords = "HEALEY ALS platform trial, adaptive platform trials, amyotrophic lateral sclerosis, clinical operations, motor neuron disease",

author = "Harkey, \{Brittney A.\} and Sofia Distefano and Pagliaro, \{Jaclyn A.\} and Lindsay Heyd and Marianne Chase and Courtney Igne and Hong Yu and Sherman, \{Alexander V.\} and Derek Dagostino and Eric Tustison and Genevive Changkuon and Meghan Hall and Gale Kittle and Connolly, \{Mariah R.\} and Elisa Giacomelli and Erica Scirocco and Berry, \{James D.\} and Suma Babu and Jeremy Shefner and Macklin, \{Eric A.\} and Chibnik, \{Lori B.\} and \{De Mattos\}, Annette and Kristin Drake and Cornelia Kamp and Andrew McGarry and Margherita Torti and Catherine Small and Allison Bulat and Cudkowicz, \{Merit E.\} and Sabrina Paganoni and Macklin, \{Eric A.\} and Chibnik, \{Lori B.\} and Douglas Hayden and Lai, \{Po Ying\} and Donahue, \{Rachel A.\} and Chen, \{Hao Wun\} and Jianing Wang and Melanie Quintana and Saville, \{Benjamin R.\} and Detry, \{Michelle A.\} and Joe Marion and Matteo Vestrucci and Anna McGlothlin and Gustavo Alameda and Nithya Mathai and Eduardo Locatelli and Gabriela Lopes and Sabrina Paganoni and Doreen Ho and Zabeen Mahuwala",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Muscle \& Nerve published by Wiley Periodicals LLC.",

year = "2025",

month = aug,

doi = "10.1002/mus.28442",

language = "English",

volume = "72",

pages = "294--305",

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T1 - Operational Development and Launch of an Adaptive Platform Trial in Amyotrophic Lateral Sclerosis

T2 - Processes and Learnings From the First Four Regimens of the HEALEY ALS Platform Trial

AU - Harkey, Brittney A.

AU - Distefano, Sofia

AU - Pagliaro, Jaclyn A.

AU - Heyd, Lindsay

AU - Chase, Marianne

AU - Igne, Courtney

AU - Yu, Hong

AU - Sherman, Alexander V.

AU - Dagostino, Derek

AU - Tustison, Eric

AU - Changkuon, Genevive

AU - Hall, Meghan

AU - Kittle, Gale

AU - Connolly, Mariah R.

AU - Giacomelli, Elisa

AU - Scirocco, Erica

AU - Berry, James D.

AU - Babu, Suma

AU - Shefner, Jeremy

AU - Macklin, Eric A.

AU - Chibnik, Lori B.

AU - De Mattos, Annette

AU - Drake, Kristin

AU - Kamp, Cornelia

AU - McGarry, Andrew

AU - Torti, Margherita

AU - Small, Catherine

AU - Bulat, Allison

AU - Cudkowicz, Merit E.

AU - Paganoni, Sabrina

AU - Macklin, Eric A.

AU - Chibnik, Lori B.

AU - Hayden, Douglas

AU - Lai, Po Ying

AU - Donahue, Rachel A.

AU - Chen, Hao Wun

AU - Wang, Jianing

AU - Quintana, Melanie

AU - Saville, Benjamin R.

AU - Detry, Michelle A.

AU - Marion, Joe

AU - Vestrucci, Matteo

AU - McGlothlin, Anna

AU - Alameda, Gustavo

AU - Mathai, Nithya

AU - Locatelli, Eduardo

AU - Lopes, Gabriela

AU - Paganoni, Sabrina

AU - Ho, Doreen

AU - Mahuwala, Zabeen

PY - 2025/8

Y1 - 2025/8

N2 - Introduction/Aims: Platform trials present several advantages over traditional interventional clinical trials. Here, we provide a detailed description of the operational framework of the HEALEY ALS Platform Trial. Methods: Platform-level procedures for regulatory oversight, safety, and site management were developed prior to trial launch. Central vendors and a single Institutional Review Board (sIRB) were used. An Investigational New Drug (IND) application was submitted for the master protocol, and each regimen was added as an amendment. Results: The HEALEY ALS Platform Trial was launched in 2020. Fifty-four geographically diverse sites from the Northeast ALS Consortium (NEALS), all highly experienced in ALS care and research, were selected. Three investigational products were selected to launch concurrently at the start of the trial as individual regimens. A fourth investigational product was selected and added to the trial after the initial launch. The Master Protocol and the first three regimens (Regimens A-C) were sIRB approved in 120 days. sIRB amendment for Regimen D was approved in 21 days. Enrollment for regimens A–C was completed in 15 months, whereas Regimen D was completed in 11 months from the start of enrollment. Results of all regimens were available within approximately 2 years from the initial trial launch. Discussion: The HEALEY ALS Platform Trial capitalized on the benefits of the platform approach, including an adaptable operational infrastructure, concurrent enrollment into four distinct regimens, and an accelerated start-up time for a new regimen added after initial trial launch.

AB - Introduction/Aims: Platform trials present several advantages over traditional interventional clinical trials. Here, we provide a detailed description of the operational framework of the HEALEY ALS Platform Trial. Methods: Platform-level procedures for regulatory oversight, safety, and site management were developed prior to trial launch. Central vendors and a single Institutional Review Board (sIRB) were used. An Investigational New Drug (IND) application was submitted for the master protocol, and each regimen was added as an amendment. Results: The HEALEY ALS Platform Trial was launched in 2020. Fifty-four geographically diverse sites from the Northeast ALS Consortium (NEALS), all highly experienced in ALS care and research, were selected. Three investigational products were selected to launch concurrently at the start of the trial as individual regimens. A fourth investigational product was selected and added to the trial after the initial launch. The Master Protocol and the first three regimens (Regimens A-C) were sIRB approved in 120 days. sIRB amendment for Regimen D was approved in 21 days. Enrollment for regimens A–C was completed in 15 months, whereas Regimen D was completed in 11 months from the start of enrollment. Results of all regimens were available within approximately 2 years from the initial trial launch. Discussion: The HEALEY ALS Platform Trial capitalized on the benefits of the platform approach, including an adaptable operational infrastructure, concurrent enrollment into four distinct regimens, and an accelerated start-up time for a new regimen added after initial trial launch.

KW - HEALEY ALS platform trial

KW - adaptive platform trials

KW - amyotrophic lateral sclerosis

KW - clinical operations

KW - motor neuron disease

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JF - Muscle and Nerve

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ER -

Operational Development and Launch of an Adaptive Platform Trial in Amyotrophic Lateral Sclerosis: Processes and Learnings From the First Four Regimens of the HEALEY ALS Platform Trial

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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