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

J 2016

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 et. al.

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

Edition

Lancet Neurology, London, UK, Elsevier, 2016, 1474-4422

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10103 Statistics and probability

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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.

Citovat

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.

@article{1364217,
   author = {Novak, Petr and Schmidt, Reinhold and Kontsekova, Eva and Zilka, Norbert and Kovacech, Branislav and Skrabana, Rostislav and VinceandKazmerova, Zuzana and Katina, Stanislav and Fialova, Lubica and Prcina, Michal and Parrak, Vojtech and DalandBianco, Peter and Brunner, Martin and Staffen, Wolfgang and Rainer, Michael and Ondrus, Matej and Ropele, Stefan and Smisek, Miroslav and Sivak, Roman and Winblad, Bengt and Novak, Michal},
   article_location = {London, UK},
   article_number = {2},
   doi = {http://dx.doi.org/10.1016/S1474-4422(16)30331-3},
   keywords = {Alzheimer's disease; a randomised; double-blind; placebo-controlled; phase 1 trial},
   language = {eng},
   issn = {1474-4422},
   journal = {Lancet Neurology},
   note = {Žádný z autorů nemá afiliaci na MU.},
   title = {Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial},
   url = {http://www.sciencedirect.com/science/article/pii/S1474442216303313},
   volume = {17},
   year = {2016}
}

TY  - JOUR
ID  - 1364217
AU  - 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
PY  - 2016
TI  - Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial
JF  - Lancet Neurology
VL  - 17
IS  - 2
SP  - 1-12
EP  - 1-12
PB  - Elsevier
SN  - 14744422
N1  - Žádný z autorů nemá afiliaci na MU.
KW  - Alzheimer's disease
KW  - a randomised
KW  - double-blind
KW  - placebo-controlled
KW  - phase 1 trial
UR  - http://www.sciencedirect.com/science/article/pii/S1474442216303313
L2  - http://www.sciencedirect.com/science/article/pii/S1474442216303313
N2  - 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.
ER  -

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. \textit{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.

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