ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer’s disease
Open accessAbstract
Alzheimer's disease (AD) pathology is partly characterized by accumulation of aberrant forms of tau protein. Here we report the results of ADAMANT, a 24-month double-blinded, parallel-arm, randomized phase 2 multicenter placebo-controlled trial of AADvac1, an active peptide vaccine designed to target pathological tau in AD (EudraCT 2015-000630-30). Eleven doses of AADvac1 were administered to patients with mild AD dementia at 40 μg per dose over the course of the trial. The primary objective was to evaluate the safety and tolerability of long-term AADvac1 treatment. The secondary objectives were to evaluate immunogenicity and efficacy of AADvac1 treatment in slowing cognitive and functional decline. A total of 196 patients were randomized 3:2 between AADvac1 and placebo. AADvac1 was safe and well tolerated (AADvac1 n = 117, placebo n = 79; serious adverse events observed in 17.1% of AADvac1-treated individuals and 24.1% of placebo-treated individuals; adverse events observed in 84.6% of AADvac1-treated individuals and 81.0% of placebo-treated individuals). The vaccine induced high levels of IgG antibodies. No significant effects were found in cognitive and functional tests on the whole study sample (Clinical Dementia Rating-Sum of the Boxes scale adjusted mean point difference -0.360 (95% CI -1.306, 0.589)), custom cognitive battery adjusted mean z-score difference of 0.0008 (95% CI -0.169, 0.172). We also present results from exploratory and post hoc analyses looking at relevant biomarkers and clinical outcomes in specific subgroups. Our results show that AADvac1 is safe and immunogenic, but larger stratified studies are needed to better evaluate its potential clinical efficacy and impact on disease biomarkers.
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Treatment with AADvac1 did not slow cognitive and functional decline in mild AD patients in the phase 2 clinical trial (ADAMANT, NCT02579252), although it shows high immunogenicity.
“However, the treatment of this vaccine did not slow cognitive and functional decline in mild AD patients in the phase 2 clinical trial (ADAMANT, NCT02579252), although it shows the high immunogenicity [227].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [227]
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- Authors
- Novak, P., Kovacech, B., Katina, S., Schmidt, R., Scheltens, P., Kontsekova, E., Ropele, S., Fialova, L., Kramberger, M., Paulenka-Ivanovova, N., Smisek, M., Hanes, J., Stevens, E., Kovac, A., Sutovsky, S., Parrak, V., Koson, P., Prcina, M., Galba, J., Cente, M., Hromadka, T., Filipcik, P., Piestansky, J., Samcova, M., Prenn-Gologranc, C., Sivak, R., Froelich, L., Fresser, M., Rakusa, M., Harrison, J., Hort, J., Otto, M., Tosun, D., Ondrus, M., Winblad, B., Novak, M., & Zilka, N.
- Affiliations
- AXON Neuroscience (Slovakia) (SK)
- University of Graz (AT)
- Amsterdam University Medical Centers (NL)
- Medical University of Graz (AT)
- Ljubljana University Medical Centre (SI)
- Heidelberg University (DE)
- AXON Neuroscience (Cyprus) (CY)
- Charles University (CZ)
- University Hospital Ulm (DE)
- University of California, San Francisco (US)
- Karolinska University Hospital (SE)
- ORCID
- Venue
- Nature Aging
- Published
- 2021-06-14
- Volume
- 1
- Issue
- 6
- Pages
- 521-534
- ISSN
- 2662-8465 (ISSN-L)
- OpenAlex
- W3167556772
- Cited by
- 187
- References
- 12
- Citations by year
- 2026: 23 · 2025: 49 · 2024: 50 · 2023: 28 · 2022: 25 · 2021: 12
- FWCI
- 18.36
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- Nature Aging (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, pathological tau, active immunotherapy, mild dementia, safety and tolerability, immunogenicity, IgG, cognitive decline, functional decline, disease biomarkers, Clinical Dementia Rating
- MeSH terms
- Alzheimer Disease, Humans, Biomarkers, Immunotherapy, Active, tau Proteins, Alzheimer Vaccines
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