Background: CAD106 is an immunotherapeutic vaccine comprising the A61-6 peptide coupled to the Q6 virus-like particle. In animals, CAD106 induced A6-antibody titers without activating A6-reactive T-cells. Admin-istration of CAD106 to APP transgenic mice showed a reduction of amyloid accumulation in the brain. Methods: Safety, toler ability and immunogenic-ity of CAD106 was assessed in a first-in-man study CCAD106A2101, a 52-week, two-center, randomized, double-blind, placebo-controlled, parallel group study in patients with mild to moderate AD in Sweden. Patients were administered 50ug CAD106/placebo at weeks 0/6/18 in Cohort I, and 150ug CAD106/placebo at weeks 0/2/6 in Cohort II. Results: 58 Cau-casians (30m, 28f) with MMSE 16-26 were randomized in two semi-over-lapping cohorts. Results of Cohort I were presented previously. The mean age was 69.3 and 68 years in Cohort I and II, respectively. One Cohort II patient discontinued the study due to withdrawal of consent at week 26. No cases of meningoencephalitis were detected clinically, and no relevant con-cerns were raised by the repeated CSF and MRI assessments. Adverse events were predominantly mild. Between the cohorts, an increase in injection-related reactions was observed in patients receiving CAD106, with the most common reaction being injection-site erythema (CAD106 Cohort I: 4%; vs CAD106 Cohort II: 64%). Serious adverse events were reported in Cohort I for 4/24 (17%) patients on CAD106 and 1/7 (14%) on placebo, and in Cohort II for 4/22 (18%) patients on CAD106 and none on placebo. All SAEs were considered unrelated to the study medication by the inves-tigator and the DSMB. CAD106 induced a measur able specific antibody re sponse against A6 in 16/24 Cohort I patients and in 18/22 Cohort II patients. Peak mean Aβ IgG antibody titers were observed at week 8 in both cohorts with a 2-fold increase observed in Cohort II. Exploratory outcome measures (clinical, CSF and MRI) did not differ significantly in either treatment group or cohort. Conclusions: Overall, the results of this study support further development of CAD106. In the two ongoing studies in Europe and the US, further data on safety, toler ability and immunogenic-ity of CAD106 150 ug administered at 0/6/12 or 0/2/6 weeks are being gathered.
Winblad, B. G., Minthon, L., Floesser, A., Imbert, G., Dumortier, T., He, Y., … Andreasen, N. (2009). O2-05-05: Results of the first-in-man study with the active Aβ Immunotherapy CAD106 in Alzheimer patients. Alzheimer’s & Dementia, 5(4S_Part_4), P113–P114. https://doi.org/10.1016/j.jalz.2009.05.356