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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Alzheimer's Research & Therapy 1/2018

Safety, tolerability and immunogenicity of an active anti-Aβ40 vaccine (ABvac40) in patients with Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase I trial

Zeitschrift:
Alzheimer's Research & Therapy > Ausgabe 1/2018
Autoren:
Ana-María Lacosta, María Pascual-Lucas, Pedro Pesini, Diego Casabona, Virginia Pérez-Grijalba, Iván Marcos-Campos, Leticia Sarasa, Jesus Canudas, Hassnae Badi, Inmaculada Monleón, Itziar San-José, Josep Munuera, Octavio Rodríguez-Gómez, Carla Abdelnour, Asunción Lafuente, Mar Buendía, Mercè Boada, Lluis Tárraga, Agustín Ruiz, Manuel Sarasa
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s13195-018-0340-8) contains supplementary material, which is available to authorized users.

Abstract

Background

Immunotherapy targeting the amyloid-β (Aβ) peptide is a promising strategy for the treatment of Alzheimer’s disease (AD); however, none of the active or passive vaccines tested have been demonstrated to be effective to date. We have developed the first active vaccine against the C-terminal end of Aβ40, ABvac40, and assessed its safety and tolerability in a phase I clinical trial.

Methods

A randomised, double-blind, placebo-controlled, parallel-group, phase I study of ABvac40 was conducted with patients aged 50–85 years with mild to moderate AD. Participants were entered into three separate groups according to time of study entry and were randomly allocated to receive ABvac40 or placebo (overall ratio 2:1). The first group received two half-doses of ABvac40 or placebo, whereas the second and third groups received two and three full doses, respectively. All treatments were administered subcutaneously at 4-week intervals. Patients, carers and investigators were blind to treatment allocation throughout the study. The primary objective was to assess the safety and tolerability of ABvac40 by registering all adverse events (AEs). All patients who received at least one dose of treatment were included in the safety analysis. The secondary objective was to evaluate the immunogenicity of ABvac40 by titration of specific anti-Aβ40 antibodies in plasma.

Results

Twenty-four patients were randomly allocated: 16 patients to the ABvac40 group and 8 patients to the placebo group. All randomised patients completed the study, therefore the intention-to-treat and safety populations were identical. Overall, 71 AEs affecting 18 patients were recorded: 11 (69%) in the ABvac40 group and 7 (88%) in the placebo group (p = 0.6214). Neither incident vasogenic oedema nor sulcal effusion (amyloid-related imaging abnormalities corresponding to vasogenic oedema and sulcal effusions) nor microhaemorrhages (amyloid-related imaging abnormalities corresponding to microhaemorrhages and hemosiderin deposits) were detected throughout the study period in the ABvac40-treated patients. Eleven of 12 (~92%) individuals receiving three injections of ABvac40 developed specific anti-Aβ40 antibodies.

Conclusions

ABvac40 showed a favourable safety and tolerability profile while eliciting a consistent and specific immune response. An ongoing phase II clinical trial is needed to confirm these results and to explore the clinical efficacy of ABvac40.

Trial registration

ClinicalTrials.gov, NCT03113812. Retrospectively registered on 14 April 2017.
Zusatzmaterial
Additional file 1: Inclusion and exclusion criteria (detailed). (DOCX 16 kb)
13195_2018_340_MOESM1_ESM.docx
Additional file 2 Randomisation (detailed). (DOCX 13 kb)
13195_2018_340_MOESM2_ESM.docx
Additional file 3: Table S1. Frequency of adverse events (detailed). (DOCX 26 kb)
13195_2018_340_MOESM3_ESM.docx
Additional file 4: Table S2. Relationship of adverse events (AEs) with the treatment. (DOCX 15 kb)
13195_2018_340_MOESM4_ESM.docx
Additional file 5: Table S3. Quantification of Aβ40 and Aβ42 levels in plasma. (DOCX 14 kb)
13195_2018_340_MOESM5_ESM.docx
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