Background: CAD106 is an immunotherapeutic vaccine comprising the Aβ1-6 peptide coupled to the Qβ virus-like particle. In animals, CAD106 induced Aβ-antibody titers without activating Aβ-reactive T-cells. Administration of CAD106 to APP transgenic mice showed a considerable reduction of amyloid accumulation. Methods: Safety, tolerability and immunogenicity of CAD106 was assessed in a first-in-man study CCAD106A2101. This was a 52-week, two-center, randomized, double-blind, placebo-controlled, time-lagged, parallel group study in patients with mild to moderate AD in Sweden. Patients underwent regular safety monitoring, which included five brain MRIs, three lumbar punctures and five electroencephalograms. An independent Data Safety Monitoring Board was monitoring the study. Results: Results are available from the first cohort of patients. This included a total of 31 Caucasians (19 m, 12 f) with a mean age of 69.3 yrs and a mean MMSE score of 21.1. At weeks 0, 6 and 18, 24 patients received 50ug of CAD106 s.c. and 7 patients received placebo. None of the 31 patients discontinued the study prior to week 52. Adverse events were reported by a total of 29 patients, and were predominantly mild. The most common adverse events were nasopharyngitis (CAD106 42% vs placebo 29%), fatigue (29% vs 0) and headache (21% vs 0). Injection-site reactions were reported by three CAD106-treated patients and one placebo-treated patient. Serious adverse events were reported for four patients on CAD106 (trauma, aorta stenosis, fainting, chest pain) and one patient on placebo. They were not considered related to the study medication. Antibody titers were measured by specific sandwich ELISA assays. CAD106 induced a specific antibody response against Aβ and against Qβ in 16 of the 24 treated patients, while no such response was observed in placebo patients. Peak mean Aβ IgG antibody titers were observed at week 8 and persisted above the defined threshold for 4 weeks. Conclusions: Overall, the results of this study indicate CAD106 50ug to be safe and well tolerated, with antibody response achieved in two thirds of the patients. A second cohort of patients was initiated based on the findings from this initial cohort. Planning for further studies is ongoing.
FULL TEXT