Randomized Controlled Trial

. 2025 Nov;72(5):1108-1116.

doi: 10.1002/mus.70011. Epub 2025 Aug 26.

Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis

Brooke Krivickas¹, Erica Scirocco¹, Elisa Giacomelli¹, Saloni Sharma¹, Molly Benson¹, Mackenzie Keegan¹, Jennifer Kulesa-Kelley¹, Lori B Chibnik¹, Gabriella Casagrande¹, Lindsay Heyd¹, Marianne Chase¹, Kristin Drake¹, Silpa Mohapatra¹, Jennifer Linn Hagar¹, Meredith Gibbons Hasenoehrl¹, Derek Dagostino¹, Alexander V Sherman¹, Alex Leite¹, Hong Yu¹, Jesse Rosenthal¹, Timothy Miller², Alexandra McCaffrey¹, Kelly Gwathmey³, Eduardo Locatelli⁴, Elham Bayat⁵, Daragh Heitzman⁶, Eufrosina Young⁷, Namita A Goyal⁸, Jackie Whitesell⁹, Kevin Felice¹⁰, Hristelina Ilieva¹¹, Andrea Swenson¹², David Walk¹³, Gustavo Alameda¹⁴, Laura Foster¹⁵, Courtney E McIlduff¹⁶, Alison Walsh¹⁷, Lindsay Zilliox¹⁸, Senda Ajroud-Driss¹⁹, Cynthia Bodkin²⁰, Jonathan Katz²¹, Shafeeq Ladha²², Michael Rivner²³, Laura Rosow²⁴, Paul Twydell²⁵, Warren Wasiewski²⁶, Suma Babu¹, James D Berry¹, Sabrina Paganoni^{1

27}

Affiliations

¹ Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Washington University School of Medicine, St. Louis, Missouri, USA.
³ Virginia Commonwealth University, Richmond, Virginia, USA.
⁴ Nova Southeastern University, Davie, Florida, USA.
⁵ George Washington University, Washington, DC, USA.
⁶ Texas Neurology, Dallas, Texas, USA.
⁷ Upstate Medical University, Syracuse, New York, USA.
⁸ University of California Irvine, Orange, California, USA.
⁹ Saint Alphonsus, Boise, Idaho, USA.
¹⁰ Hospital for Special Care, New Britain, Connecticut, USA.
¹¹ Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
¹² University of Iowa, Iowa City, Iowa, USA.
¹³ University of Minnesota, Minneapolis, Minnesota, USA.
¹⁴ Holy Cross Hospital, Fort Lauderdale, Florida, USA.
¹⁵ University of Colorado Anschutz, Aurora, Colorado, USA.
¹⁶ Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
¹⁷ Lehigh Valley Health Network, Allentown, Pennsylvania, USA.
¹⁸ University of Maryland School of Medicine, Baltimore, Maryland, USA.
¹⁹ Northwestern University, Chicago, Illinois, USA.
²⁰ Indiana University, Indianapolis, Indiana, USA.
²¹ California Pacific Medical Center, San Francisco, California, USA.
²² Barrow Neurological Institute, Phoenix, Arizona, USA.
²³ Augusta University, Augusta, Georgia, USA.
²⁴ University of California San Francisco, San Francisco, California, USA.
²⁵ Spectrum Health, Grand Rapids, Michigan, USA.
²⁶ Seelos Therapeutics, New York, New York, USA.
²⁷ Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 40857020
PMCID: PMC12428506
DOI: 10.1002/mus.70011

Randomized Controlled Trial

Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis

Brooke Krivickas et al. Muscle Nerve. 2025 Nov.

. 2025 Nov;72(5):1108-1116.

doi: 10.1002/mus.70011. Epub 2025 Aug 26.

Authors

Affiliations

¹ Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Washington University School of Medicine, St. Louis, Missouri, USA.
³ Virginia Commonwealth University, Richmond, Virginia, USA.
⁴ Nova Southeastern University, Davie, Florida, USA.
⁵ George Washington University, Washington, DC, USA.
⁶ Texas Neurology, Dallas, Texas, USA.
⁷ Upstate Medical University, Syracuse, New York, USA.
⁸ University of California Irvine, Orange, California, USA.
⁹ Saint Alphonsus, Boise, Idaho, USA.
¹⁰ Hospital for Special Care, New Britain, Connecticut, USA.
¹¹ Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
¹² University of Iowa, Iowa City, Iowa, USA.
¹³ University of Minnesota, Minneapolis, Minnesota, USA.
¹⁴ Holy Cross Hospital, Fort Lauderdale, Florida, USA.
¹⁵ University of Colorado Anschutz, Aurora, Colorado, USA.
¹⁶ Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
¹⁷ Lehigh Valley Health Network, Allentown, Pennsylvania, USA.
¹⁸ University of Maryland School of Medicine, Baltimore, Maryland, USA.
¹⁹ Northwestern University, Chicago, Illinois, USA.
²⁰ Indiana University, Indianapolis, Indiana, USA.
²¹ California Pacific Medical Center, San Francisco, California, USA.
²² Barrow Neurological Institute, Phoenix, Arizona, USA.
²³ Augusta University, Augusta, Georgia, USA.
²⁴ University of California San Francisco, San Francisco, California, USA.
²⁵ Spectrum Health, Grand Rapids, Michigan, USA.
²⁶ Seelos Therapeutics, New York, New York, USA.
²⁷ Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 40857020
PMCID: PMC12428506
DOI: 10.1002/mus.70011

Abstract

Introduction/aims: Expanded access protocols (EAPs) allow individuals ineligible for clinical trials to receive investigational products. EAP data can be collected in parallel to randomized clinical trials (RCTs) and serve as a source of evidence in clinical practice. Here, we present the results of a National Institutes of Health (NIH)-funded EAP for amyotrophic lateral sclerosis (ALS).

Methods: Participants received trehalose, a drug studied in a parallel RCT, for up to 24 weeks; clinical and biomarker data were collected throughout the study.

Results: Seventy participants were enrolled at 20 study centers across the United States. Treatment with trehalose did not affect the levels of neurofilament light chain [estimated flat slope per month was -0.005, SE = 0.0078; 95% CI (-0.021, 0.011)] or disease progression [estimated least square mean change of the ALS Functional Rating Scale-Revised total score and slow vital capacity (percent predicted) from baseline to Week 24 were -5.6 (0.67); 95% CI (-7.0, -4.3) and -4.53 (4.308); 95% CI (-13.55, 4.48)], respectively. No unexpected treatment-related risks were identified. Serious adverse events were deemed not related to trehalose (20 occurrences in 13 [18.6%] participants with eight deaths).

Discussion: This EAP establishes a framework for implementing multi-center EAPs that complement data collected from RCTs. Additional NIH-funded EAPs are currently underway. Data and additional serum samples collected in this study are available to the research community for further study.

Trial registration: ClinicalTrials.gov: NCT05597436.

Keywords: amyotrophic lateral sclerosis; expanded access; investigational product; motor neuron disease; trehalose.

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Conflict of interest statement

Dr. Senda Ajroud‐Driss reports research support from Biogen, Amylyx, Mitsubishi Tanabe Pharma America, Alnylam, Novartis, Sanofi, and reports personal consulting fees from Biogen and Amylyx and served as a paid educational presenter for Biogen. Dr. Suma Babu has received research funding from AANEM Foundation, American Academy of Neurology, ALS Association, Muscular Dystrophy Association, Biogen, Orion Pharma, Novartis, Medicinova, Ionis, and AI therapeutics. Dr. James D. Berry reports research grants from Biogen, MT Pharma of America, Alexion, Rapa Therapeutics, the ALS Association, the Muscular Dystrophy Association, ALS One, Tambourine, ALS Finding a Cure, and reports personal consulting fees from Biogen, Clene Nanomedicine, MT Pharma of America, and Janssen. Dr. Cynthia Bodkin reports research grants from Icon Clinical Research LLC, Cytokinetics, Alector LLC, Atlantic Research Group, Amicus Therapeutics, Alexion Pharmaceuticals Inc., Medicinova Inc., RA Pharmaceuticals Inc., Edgewise, and Acceleron Pharma Inc., and reports consulting fees from Alexion. Dr. Namita A. Goyal has served on Advisory Boards for Abcuro, Alexion, Amylyx, Annexon, Argenx, Astrazeneca, CSL Behring, Fulcrum, Kezar, and Octapharma. She has received research grants from Abcuro, Alexion, Amylyx, Annexon, Calico, Clene, Fulcrum, Janssen, Medicinova, PepGen, Prilenia, PTC, Rapa, Roche, Sanofi, and Transposon. She has also served on the speaker's bureau for Argenx and CSL. Dr. Kelly Gwathmey has received consulting and speaking honoraria from Alexion Pharmaceuticals, consulting honoraria from Argenx and UCB Pharmaceuticals. Dr. Daragh Heitzman has received ALS clinic support from the Muscular Dystrophy Association and ALS Association. He has received research support from Biohaven, Clene Nanomedicine, Eledon, Prilenia, Seelos, Ra, Cytokinetics, Abcuro, AbbVie, Immunovant Sciences, Calico, Denali, Revance, Mitsubishi Tanabe, and Amylyx. He has performed consultant work for Amylyx. Dr. Shafeeq Ladha has received research funding from Clene, Sanofi, Annexon, Amylyx, Genentech, ALSA, and NIH. He has received consulting fees from Sanofi, Amylyx, Genentech, Annexon, Apellis, NeuroSense, UCB Pharma, and Amicus. Dr. Courtney E. McIlduff has received ALS clinic support from the ALS Association. She has received research support from the Blavatnik Family Foundation, NIH, and the US DOD Army CDMRP Program (ALSRP). Dr. Sabrina Paganoni reports research grants from Amylyx Therapeutics, Revalesio Corporation, Alector, Eledon, UCB, Biohaven, Clene Nanomedicine, Prilenia, Seelos, Calico, Denali, NIH, CDC, DoD, The ALS Association, the American Academy of Neurology, ALS Finding a Cure, the Salah Foundation, the Spastic Paraplegia Foundation, the Muscular Dystrophy Association, and Tambourine, and reports consulting fees from Amylyx, Orion, Medscape, Arrowhead, and Cytokinetics. Dr. Laura Rosow receives salary support from The ALS Association and contract research support from Mitsubishi Tanabe Pharma America, Seelos Therapeutics, Denali Therapeutics, Calico, AbbVie, and Abcuro. Mr. Alexander V. Sherman reports research grants from The ALS Association, ALS Finding a Cure, and the NIH. Dr. David Walk reports research support from the FDA and Minnesota Office of Higher Education, consulting fees from Biogen, Amylyx, and Mitsubishi Tanabe Pharma America, and serves on a regional board of the ALS Association. Dr. Jackie Whitesell reports research funding from the ALS Association. She does not serve on an advisory board, and she does not receive compensation for consultation. Dr. Eufrosina Young received research support for her institution from Mitsubishi Tanabe Pharma America. Dr. Warren Wasiewski was the Senior Neurologist for Seelos Therapeutics. The other authors declare no conflicts of interest.

Figures

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Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis

Affiliations

Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

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Grants and funding

LinkOut - more resources

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