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ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer's disease.
Novak, Petr; Kovacech, Branislav; Katina, Stanislav; Schmidt, Reinhold; Scheltens, Philip; Kontsekova, Eva; Ropele, Stefan; Fialova, Lubica; Kramberger, Milica; Paulenka-Ivanovova, Natalia; Smisek, Miroslav; Hanes, Jozef; Stevens, Eva; Kovac, Andrej; Sutovsky, Stanislav; Parrak, Vojtech; Koson, Peter; Prcina, Michal; Galba, Jaroslav; Cente, Martin; Hromadka, Tomas; Filipcik, Peter; Piestansky, Juraj; Samcova, Maria; Prenn-Gologranc, Carmen; Sivak, Roman; Froelich, Lutz; Fresser, Michal; Rakusa, Martin; Harrison, John; Hort, Jakub; Otto, Markus; Tosun, Duygu; Ondrus, Matej; Winblad, Bengt; Novak, Michal; Zilka, Norbert.
Afiliación
  • Novak P; AXON Neuroscience CRM Services SE, Bratislava, Slovakia. petr.novak@axon-neuroscience.eu.
  • Kovacech B; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Katina S; AXON Neuroscience CRM Services SE, Bratislava, Slovakia.
  • Schmidt R; Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, Graz, Austria.
  • Scheltens P; Alzheimer Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
  • Kontsekova E; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Ropele S; Clinical Division of General Neurology, Department of Neurology, Medical University Graz, Graz, Austria.
  • Fialova L; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Kramberger M; Department of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
  • Paulenka-Ivanovova N; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Smisek M; AXON Neuroscience CRM Services SE, Bratislava, Slovakia.
  • Hanes J; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Stevens E; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Kovac A; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Sutovsky S; 1st Department of Neurology, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovakia.
  • Parrak V; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Koson P; AXON Neuroscience CRM Services SE, Bratislava, Slovakia.
  • Prcina M; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Galba J; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Cente M; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Hromadka T; Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.
  • Filipcik P; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Piestansky J; AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
  • Samcova M; AXON Neuroscience CRM Services SE, Bratislava, Slovakia.
  • Prenn-Gologranc C; AXON Neuroscience CRM Services SE, Bratislava, Slovakia.
  • Sivak R; AXON Neuroscience CRM Services SE, Bratislava, Slovakia.
  • Froelich L; Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, Medical Faculty Mannheim University of Heidelberg, Heidelberg, Germany.
  • Fresser M; AXON Neuroscience SE, Larnaca, Cyprus.
  • Rakusa M; Department of Neurological Diseases, University Medical Centre Maribor, Maribor, Slovenia.
  • Harrison J; Alzheimer Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
  • Hort J; Memory Clinic, Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
  • Otto M; Department of Neurology, Ulm University Hospital, Ulm, Germany.
  • Tosun D; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
  • Ondrus M; AXON Neuroscience CRM Services SE, Bratislava, Slovakia.
  • Winblad B; Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Solna, Sweden.
  • Novak M; Theme Inflammation and Aging, Karolinska University Hospital, Huddinge, Sweden.
  • Zilka N; AXON Neuroscience SE, Larnaca, Cyprus.
Nat Aging ; 1(6): 521-534, 2021 06.
Article en En | MEDLINE | ID: mdl-37117834
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Tipo de estudio: Clinical_trials Límite: Humans Idioma: En Revista: Nat Aging Año: 2021 Tipo del documento: Article País de afiliación: Eslovaquia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Tipo de estudio: Clinical_trials Límite: Humans Idioma: En Revista: Nat Aging Año: 2021 Tipo del documento: Article País de afiliación: Eslovaquia Pais de publicación: Estados Unidos