Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study
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Winblad, Bengt, Andreasen, Niels, Minthon, Lennart, Floesser, Annette, Imbert, Georges, Dumortier, Thomas, Maguire, Paul, blennow, Kaj, lundmark, joens, Staufenbiel, Matthias, orgogozo, jean-marc and Graf, Ana (2012) Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study. Lancet Neurology.
Abstract
Summary
Background Immunotherapy targeting the amyloid β (Aβ) peptide is a potential strategy to slow the progression of
Alzheimer’s disease. We aimed to assess the safety and tolerability of CAD106, a novel active Aβ immunotherapy for patients
with Alzheimer’s disease, designed to induce N-terminal Aβ-specifi c antibodies without an Aβ-specifi c T-cell response.
Methods We did a phase 1, double-blind, placebo-controlled, 52-week study in two centres in Sweden. Participants, aged
50–80 years, with mild-to-moderate Alzheimer’s disease were entered into one of two cohorts according to time of study
entry and then randomly allocated (by use of a computer-generated randomisation sequence) to receive either CAD106
or placebo (4:1; cohort one received CAD106 50 μg or placebo, cohort two received CAD106 150 μg or placebo). Each
patient received three subcutaneous injections. All patients, caregivers, and investigators were masked to treatment
allocation throughout the study. Primary objectives were to assess the safety and tolerability of CAD106 and to identify
the Aβ-specifi c antibody response. Safety assessment was done by recording of all adverse events, assessment of MRI
scans, physical and neurological examinations, vital signs, electrocardiography, electroencephalography, and laboratory
analysis of blood and CSF. Patients with Aβ-IgG serum titres higher than 16 units at least once during the study were
classifi ed as responders. This study is registered with ClinicalTrials.gov, number NCT00411580.
Findings Between August, 2005, and March, 2007, we randomly allocated 31 patients into cohort one (24 patients to
CAD106 treatment and seven to placebo) and 27 patients into cohort two (22 patients to CAD106 treatment and fi ve to
placebo). 56 of 58 patients reported adverse events. In cohort one, nasopharyngitis was the most commonly reported
adverse event (10 of 24 CAD106-treated patients). In cohort two, injection site erythema was the most commonly
reported adverse event (14 of 22 CAD106-treated patients). Overall, nine patients reported serious adverse events—
none was thought to be related to the study drug. We recorded no clinical or subclinical cases of meningoencephalitis.
16 of 24 (67%) CAD106-treated patients in cohort one and 18 of 22 (82%) in cohort two developed Aβ antibody response
meeting pre-specifi ed responder threshold. One of 12 placebo-treated patients (8%) had Aβ-IgG concentrations that
qualifi ed them as a responder.
Interpretation Our fi ndings suggest that CAD106 has a favourable safety profi le and acceptable antibody response in
patients with Alzheimer’s disease. Larger trials with additional dose investigations are needed to confi rm the safety
and establish the effi cacy of CAD106.
| Item Type: | Article |
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| Additional Information: | Published online June 6, 2012 |
| Keywords: | CAD106, Alzheimer's disease, immunotherapy, imaging |
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| Date Deposited: | 13 Oct 2015 13:14 |
| Last Modified: | 13 Oct 2015 13:14 |
| URI: | https://oak.novartis.com/id/eprint/7956 |