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Efficacy assessment...
Efficacy assessment of an active tau immunotherapy in Alzheimer's disease patients with amyloid and tau pathology : a post hoc analysis of the “ADAMANT” randomised, placebo-controlled, double-blind, multi-centre, phase 2 clinical trial
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- Cullen, Nicholas C. (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Novak, Petr (author)
- Axon Neuroscience SE
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- Tosun, Duygu (author)
- San Francisco Veterans Administration Medical Center,University of California, San Francisco
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- Kovacech, Branislav (author)
- Axon Neuroscience SE
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Hanes, Jozef (author)
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Kontsekova, Eva (author)
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- Fresser, Michal (author)
- Axon Neuroscience SE
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- Ropele, Stefan (author)
- Medical University of Graz
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Feldman, Howard H. (author)
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- Schmidt, Reinhold (author)
- Medical University of Graz
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- Winblad, Bengt (author)
- Karolinska Institutet,Karolinska University Hospital
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- Zilka, Norbert (author)
- Axon Neuroscience SE
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: EBioMedicine. - 2352-3964. ; 99
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Abstract
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- Background: Tau pathology correlates with and predicts clinical decline in Alzheimer's disease. Approved tau-targeted therapies are not available. Methods: ADAMANT, a 24-month randomised, placebo-controlled, parallel-group, double-blinded, multicenter, Phase 2 clinical trial (EudraCT2015-000630-30, NCT02579252) enrolled 196 participants with Alzheimer's disease; 119 are included in this post-hoc subgroup analysis. AADvac1, active immunotherapy against pathological tau protein. A machine learning model predicted likely Amyloid+Tau+ participants from baseline MRI. Statistical methods: MMRM for change from baseline in cognition, function, and neurodegeneration; linear regression for associations between antibody response and endpoints. Results: The prediction model achieved PPV of 97.7% for amyloid, 96.2% for tau. 119 participants in the full analysis set (70 treatment and 49 placebo) were classified as A+T+. A trend for CDR-SB 104-week change (estimated marginal means [emm] = −0.99 points, 95% CI [−2.13, 0.13], p = 0.0825]) and ADCS-MCI-ADL (emm = 3.82 points, CI [−0.29, 7.92], p = 0.0679) in favour of the treatment group was seen. Reduction was seen in plasma NF-L (emm = −0.15 log pg/mL, CI [−0.27, −0.03], p = 0.0139). Higher antibody response to AADvac1 was related to slowing of decline on CDR-SB (rho = −0.10, CI [−0.21, 0.01], p = 0.0376) and ADL (rho = 0.15, CI [0.03, 0.27], p = 0.0201), and related to slower brain atrophy (rho = 0.18–0.35, p < 0.05 for temporal volume, whole cortex, and right and left hippocampus). Conclusions: In the subgroup of ML imputed or CSF identified A+T+, AADvac1 slowed AD-related decline in an antibody-dependent manner. Larger anti-tau trials are warranted. Funding: AXON Neuroscience SE.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimer's disease
- Immunotherapy
- Machine learning
- Post-hoc analysis
- Tau
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Cullen, Nicholas ...
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Novak, Petr
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Tosun, Duygu
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Kovacech, Branis ...
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Hanes, Jozef
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Kontsekova, Eva
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Fresser, Michal
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Ropele, Stefan
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Feldman, Howard ...
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Schmidt, Reinhol ...
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Winblad, Bengt
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Zilka, Norbert
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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EBioMedicine
- By the university
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Lund University
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Karolinska Institutet