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O2‐05‐05: Results of the first‐in‐man study with the active Aβ Immunotherapy CAD106 in Alzheimer patients
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2009
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ImmunodeficienciesImmunologyAlzheimer PatientsImmunodominanceNeurochemical BiomarkersImmunotherapeuticsImmunotherapyAmyloid AccumulationAlzheimer's DiseaseVaccine SurveillanceVaccine TrialNeurologyAging-associated DiseaseNeuropathologyNeuroimmunologyVaccine DevelopmentMedicineTherapeutic VaccineHumoral ImmunityT Cell ImmunityImmune FunctionNeurodegenerationFirst‐in‐man StudyProtective MechanismsCad106 150VaccinationNeurodegenerative DiseasesVaccine EfficacyNeurosciencePrecision VaccinologyVaccine ResearchCad106 Cohort
CAD106 is an immunotherapeutic vaccine comprising the Aß1-6 peptide coupled to the Qß virus-like particle. In animals, CAD106 induced Aß-antibody titers without activating Aß-reactive T-cells. Administration of CAD106 to APP transgenic mice showed a reduction of amyloid accumulation in the brain. Safety, tolerability and immunogenicity 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. 58 Caucasians (30m, 28f) with MMSE 16-26 were randomized in two semi-overlapping 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 concerns 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 investigator and the DSMB. CAD106 induced a measurable specific antibody response against Aß in 16/24 Cohort I patients and in 18/22 Cohort II patients. Peak mean Aß 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. 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, tolerability and immunogenicity of CAD106 150 ug administered at 0/6/12 or 0/2/6 weeks are being gathered.