Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial

NOVAK, Petr, Reinhold SCHMIDT, Eva KONTSEKOVA, Norbert ZILKA, Branislav KOVACECH, Rostislav SKRABANA, Zuzana VINCE-KAZMEROVA, Stanislav KATINA, Lubica FIALOVA, Michal PRCINA, Vojtech PARRAK, Peter DAL-BIANCO, Martin BRUNNER, Wolfgang STAFFEN, Michael RAINER, Matej ONDRUS, Stefan ROPELE, Miroslav SMISEK, Roman SIVAK, Bengt WINBLAD and Michal NOVAK. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurology. London, UK: Elsevier, 2016, vol. 17, No 2, p. 1-12. ISSN 1474-4422. Available from: https://dx.doi.org/10.1016/S1474-4422(16)30331-3.

Basic information

• Original name: Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial
• Authors: NOVAK, Petr, Reinhold SCHMIDT, Eva KONTSEKOVA, Norbert ZILKA, Branislav KOVACECH, Rostislav SKRABANA, Zuzana VINCE-KAZMEROVA, Stanislav KATINA, Lubica FIALOVA, Michal PRCINA, Vojtech PARRAK, Peter DAL-BIANCO, Martin BRUNNER, Wolfgang STAFFEN, Michael RAINER, Matej ONDRUS, Stefan ROPELE, Miroslav SMISEK, Roman SIVAK, Bengt WINBLAD and Michal NOVAK.
• Edition: Lancet Neurology, London, UK, Elsevier, 2016, 1474-4422.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10103 Statistics and probability
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL URL
• Impact factor: Impact factor: 26.284
• Organization unit: Faculty of Science
• Doi: http://dx.doi.org/10.1016/S1474-4422(16)30331-3
• Keywords in English: Alzheimer's disease; a randomised; double-blind; placebo-controlled; phase 1 trial
• Tags: AKR
• Tags: International impact, Reviewed

Abstract

Neurofibrillary pathology composed of tau protein is a main correlate of cognitive impairment in patients with Alzheimer's disease. Immunotherapy targeting pathological tau proteins is therefore a promising strategy for disease-modifying treatment of Alzheimer's disease. We have developed an active vaccine, AADvac1, against pathological tau proteins and assessed it in a phase 1 trial. We did a first-in-man, phase 1, 12 week, randomised, double-blind, placebo-controlled study of AADvac1 with a 12 week open-label extension in patients aged 50–85 years with mild-to-moderate Alzheimer's disease at four centres in Austria. We randomly assigned patients with a computer-generated sequence in a 4:1 ratio overall to receive AADvac1 or placebo. They received three subcutaneous doses of AADvac1 or placebo from masked vaccine kits at monthly intervals, and then entered the open-label phase, in which all patients were allocated to AADvac1 treatment and received another three doses at monthly intervals. Patients, carers, and all involved with the trial were masked to treatment allocation. The primary endpoint was all-cause treatment-emergent adverse events, with separate analyses for injection site reactions and other adverse events. We include all patients who received at least one dose of AADvac1 in the safety assessment. Patients who had a positive IgG titre against the tau peptide component of AADvac1 at least once during the study were classified as responders. The first-in-man study is registered with EU Clinical Trials Register, number EudraCT 2012-003916-29, and ClinicalTrials.gov, number NCT01850238; the follow-up study, which is ongoing, is registered with EU Clinical Trials Register, number EudraCT 2013-004499-36, and ClinicalTrials.gov, number NCT02031198.