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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. (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Novak, Petr (författare)
- Axon Neuroscience SE
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- Tosun, Duygu (författare)
- San Francisco Veterans Administration Medical Center,University of California, San Francisco
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- Kovacech, Branislav (författare)
- Axon Neuroscience SE
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Hanes, Jozef (författare)
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Kontsekova, Eva (författare)
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- Fresser, Michal (författare)
- Axon Neuroscience SE
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- Ropele, Stefan (författare)
- Medical University of Graz
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Feldman, Howard H. (författare)
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- Schmidt, Reinhold (författare)
- Medical University of Graz
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- Winblad, Bengt (författare)
- Karolinska Institutet,Karolinska University Hospital
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- Zilka, Norbert (författare)
- Axon Neuroscience SE
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(creator_code:org_t)
- 2024
- 2024
- Engelska.
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Ingår i: EBioMedicine. - 2352-3964. ; 99
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Alzheimer's disease
- Immunotherapy
- Machine learning
- Post-hoc analysis
- Tau
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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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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visa fler...
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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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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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EBioMedicine
- Av lärosätet
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Lunds universitet
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Karolinska Institutet