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; SCHMIDT Reinhold; KONTSEKOVA Eva; ZILKA Norbert; KOVACECH Branislav; SKRABANA Rostislav; VINCE-KAZMEROVA Zuzana; KATINA Stanislav; FIALOVA Lubica; PRCINA Michal; PARRAK Vojtech; DAL-BIANCO Peter; BRUNNER Martin; STAFFEN Wolfgang; RAINER Michael; ONDRUS Matej; ROPELE Stefan; SMISEK Miroslav; SIVAK Roman; WINBLAD Bengt; NOVAK Michal
• Year of publication: 2016
• Type: Article in Periodical
• Magazine / Source: Lancet Neurology
• MU Faculty or unit: Faculty of Science

Web

• http://www.sciencedirect.com/science/article/pii/S1474442216303313
• http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(16)30331-3/fulltext

• Doi: http://dx.doi.org/10.1016/S1474-4422(16)30331-3
• Field: Applied statistics, operation research
• Keywords: Alzheimer's disease; a randomised; double-blind; placebo-controlled; phase 1 trial
• Description: 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.