TY - JOUR
T1 - ASURE Clinical Trial Protocol
T2 - A Randomized, Placebo-Controlled, Proof-of-Concept Study Aiming to Evaluate Safety and Target Engagement following Administration of TW001 in Early Alzheimer’s Disease Patients
AU - Oosthoek, Marlies
AU - Lili, A.
AU - Almeida, A.
AU - van Loosbroek, O.
AU - van der Geest, R.
AU - de Greef-van der Sandt, I.
AU - van Bokhoven, P.
AU - Sikkes, S.A.M.
AU - Teunissen, C.E.
AU - Vijverberg, E.G.B.
N1 - Funding Information: Funding: This trial is kindly sponsored by the Alzheimer’s Drug Discovery Foundation. Funding Information: Disclosures: MO has received consultancy fees from New Amsterdam Pharma (paid to the institute). PvB declares that he has no competing interests. PvB is an advisory consultant for several pharmaceutical companies in the field of neurodegeneration. Research of CET is supported by the European Commission (Marie Curie International Training Network, grant agreement No 860197 (mIRIADE), Innovative Medicines Initiatives 3TR (Horizon 2020, grant no 831434) EPND (FMI 2 Joint Undertaking (JU), grant No. 101034344) and JPND (bPRIDE), National MS Society (Progressive MS alliance), Alzheimer Association, Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands. CT is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health-Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). CET has a collaboration contract with ADx Neurosciences, Quanterix and Eli Lilly, performed contract research or received grants from AC-Immune, Axon Neurosciences, BioConnect, Bioorchestra, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, Fujirebio, Grifols, Instant Nano Biosensors, Merck, Novo Nordisk, PeopleBio, Roche, Siemens, Toyama, Vivoryon. CET serves on editorial boards of Medidact Neurologie/Springer, Alzheimer Research and Therapy, Neurology: Neuroimmunology & Neuroinflammation. EGBV has received consultancy fees (paid to institute) for New Amsterdam Pharma, Treeway, ReMynd, Vivoryon, Biogen, Vigil Neuroscience, ImmunoBrain Checkpoint en Roche. Within his university affiliation he is PI of studies of DIAN, AC immune, Alnylam, CogRX therapeutics, New Amsterdam Pharma, Janssen, UCB, Roche, Vivoryon, ImmunoBrain, GemVax and Alector. Sub-Investigator from Eli Lilly, Biogen en Fuij Film Toyama. Co-founder van het CANDIDATE Center Amsterdam UMC. Publisher Copyright: © 2023, The Authors.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - Background: Alzheimer’s disease (AD) is a neurodegenerative disease with complex disease etiology and pathological processes. These include formation of plaques and tangles, aberrant lipid processing, neuroinflammation, cerebrovascular dysregulation, ion channel and mitochondrial dysfunction, and oxidative stress. Disease-modifying therapies focusing on all these different facets are needed. TW001 is an oral formulation with the radical scavenger edaravone as its active ingredient, targeting oxidative stress. Objectives: This manuscript describes the trial design for Phase IIA Alzheimer Study Using oRal Edaravone (ASURE). Methods: ASURE is a randomized, placebo-controlled, proof-of-concept study aiming to evaluate safety and target engagement following administration of TW001 in early AD patients. Patients should have a biomarker confirmed diagnosis to be included in the trial and will be treated for 90 days. The primary endpoints include safety and effect of TW001 on oxidative stress biomarkers. Exploratory endpoints focus on a panel of AD(-related) fluid-based biomarkers and EEG. In addition, a recently developed cognitive functional composite (CFC) score will measure early signs of cognitive and functional effects of TW001. Results: This article outlines the design of the clinical study, no results are included. Conclusions: The ASURE trial design is discussed, with a particular focus on fluid biomarkers, EEG, and CFC as endpoints. By testing multiple measures related to pathology, pharmacodynamics, EEG as proxy for cognition, and cognitive functional scores, it is expected that small changes will be detectable in trials of shorter duration. Moreover, the wide range of endpoints allows to make well-informed decisions for designing pivotal studies later.
AB - Background: Alzheimer’s disease (AD) is a neurodegenerative disease with complex disease etiology and pathological processes. These include formation of plaques and tangles, aberrant lipid processing, neuroinflammation, cerebrovascular dysregulation, ion channel and mitochondrial dysfunction, and oxidative stress. Disease-modifying therapies focusing on all these different facets are needed. TW001 is an oral formulation with the radical scavenger edaravone as its active ingredient, targeting oxidative stress. Objectives: This manuscript describes the trial design for Phase IIA Alzheimer Study Using oRal Edaravone (ASURE). Methods: ASURE is a randomized, placebo-controlled, proof-of-concept study aiming to evaluate safety and target engagement following administration of TW001 in early AD patients. Patients should have a biomarker confirmed diagnosis to be included in the trial and will be treated for 90 days. The primary endpoints include safety and effect of TW001 on oxidative stress biomarkers. Exploratory endpoints focus on a panel of AD(-related) fluid-based biomarkers and EEG. In addition, a recently developed cognitive functional composite (CFC) score will measure early signs of cognitive and functional effects of TW001. Results: This article outlines the design of the clinical study, no results are included. Conclusions: The ASURE trial design is discussed, with a particular focus on fluid biomarkers, EEG, and CFC as endpoints. By testing multiple measures related to pathology, pharmacodynamics, EEG as proxy for cognition, and cognitive functional scores, it is expected that small changes will be detectable in trials of shorter duration. Moreover, the wide range of endpoints allows to make well-informed decisions for designing pivotal studies later.
KW - Alzheimer
KW - clinical trial design
KW - oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85174826032&partnerID=8YFLogxK
U2 - https://doi.org/10.14283/jpad.2023.107
DO - https://doi.org/10.14283/jpad.2023.107
M3 - Article
C2 - 37874087
SN - 2274-5807
VL - 10
SP - 669
EP - 674
JO - Journal of Prevention of Alzheimer's Disease
JF - Journal of Prevention of Alzheimer's Disease
IS - 4
ER -