Active Aβ immunotherapy CAD106 in Alzheimer's disease: A phase 2b study

Rik Vandenberghe, Marie-Emmanuelle Riviere, Angelika Caputo, Judit Sovago, R Paul Maguire, Martin Farlow, Giovanni Marotta, Raquel Sanchez-Valle, Philip Scheltens, J Michael Ryan, Ana Graf

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

INTRODUCTION: This randomized, double-blind, placebo-controlled, 90-week study assessed safety, tolerability, and immunogenicity of CAD106 with/without adjuvant in patients with mild Alzheimer's disease.

METHODS: One hundred twenty-one patients received up to seven intramuscular injections of CAD106 (150 μg or 450 μg) or placebo ± adjuvant over 60 weeks. An amyloid positron emission tomography (PET) substudy was also conducted.

RESULTS: CAD106 induced strong serological responses (amyloid-beta [Aβ]-Immunoglobuline G[IgG]) in 55.1% (150 μg) and 81.1% (450 μg) of patients (strong serological responders [SSRs]). Serious adverse events (SAEs) were reported in 24.5% (95% confidence interval [CI] 16.7-33.8) of the patients in the active treatment group and in 6.7% (95% CI 0.2-31.9) in the placebo group. Three of the SAEs were classified as possibly related to study drug by the investigators. No evidence of central nervous system inflammation was found. Amyloid-related imaging abnormalities (ARIAs) occurred in six cases, all of them were strong serological responders. None of the ARIAs were symptomatic. Serum Aβ-IgG titer area under the curves correlated negatively with amyloid PET standardized uptake value ratio percentage change from baseline to week 78 within the CAD106-treated patients (r = -0.84, P = .0004). Decrease in cortical gray-matter volume from baseline to week 78 was larger in SSRs than in controls (P = .0077).

DISCUSSION: Repeated CAD106 administration was generally well tolerated. CAD106 450 μg with alum adjuvant demonstrated the best balance between antibody response and tolerability.

Original languageEnglish
Pages (from-to)10-22
Number of pages13
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume3
Issue number1
DOIs
Publication statusPublished - Jan 2017

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