A 90-week, multi-center, randomized, double-blind, placebo-controlled study in patients with mild Alzheimer’s Disease (AD) to investigate the safety, tolerability and Abeta-specific antibody response following repeated i.m. injections of adjuvanted CAD106

INTERVENTION: Product Name: CAD106 Product Code: CAD106A Pharmaceutical Form: Powder and solvent for solution for injection INN or Proposed INN: Not available yet CAS Number: N/A Current Sponsor code: CAD106A Other descriptive name: CAD106 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.5‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Intramuscular use CONDITION: Alzheimer's Disease. ; MedDRA version: 13.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] SECONDARY OUTCOME: Secondary end point(s): As listed in protocol section 9.5 Timepoint(s) of evaluation of this end point: 22 visits post baseline over 90 weeks (details see protocol table 6‐1). INCLUSION CRITERIA: 1. Written informed consent obtained before any assessment is performed according to local requirements for obtaining consent in mild AD patients. 2. Male and female patients below the age of 85 years. 3. Female patients must be without childbearing potential (post‐menopausal or surgically sterilized). 4. Diagnosis of dementia of the Alzheimer’s type according to the DSM‐IV criteria. 5. Patients who satisfy the criteria for a clinical diagnosis of probable AD. 6. Mild AD as confirmed by a MMSE score of 20 to 26 (both inclusive) at screening, and either untreated or on stable dose of cholinesterase inhibitor and/or other AD treatment over the last 4 weeks prior to the clinical assessments. 7. Sufficient education to have been able to read, write, and communicate effectively during the pre‐morbid state. 8. Cooperative, willing to complete all aspects and attend all visits of the study including lumbar puncture/CSF samplings (primarily f PRIMARY OUTCOME: Main Objective: • To assess the safety and tolerability of up to 7 repeated injections of CAD106 with or without adjuvant (Alum or MF59) in patients with mild Alzheimer’s Disease (AD) over 90 weeks.; • To compare the immunogenicity of CAD106 with Alum or MF59 in patients with mild Alzheimer’s Disease (AD) as measured by the titers of Aß‐specific IgG in serum across regimens and in reference to non‐adjuvanted CAD106. Primary end point(s): •Adverse events, serious adverse events, discontinuation due to an AE; •Cerebral safety MRI (including signs of inflammation,; microhemorrhages, and other findings); •CSF findings related to inflammation (white blood cells, IgG index,; oligoclonal bands in blood and CSF); •All other safety assessments (eg. laboratory tests, ECGs, vital signs); •Injection‐related reactions from the adverse events and the patient's; diary such as Bruising (Ecchymosis), Redness, Induration, Swelling,; Local pain, Chills, Malaise, Muscle pain (Myalgia), Joint pain (Arthralgia),; Headache, Sweating, and Fatigue; •Immune response after repeated up to 7 injections of CAD106 in each; treatment arm as measured primarily by the profile of Abeta‐specific IgG; titers in serum. The immune response will be assessed by CMAX, TMAX,; and AUC (area under the curve) and by responders status. Secondary Objective: • To characterize the Aß‐ and Qß‐specific antibody response to CAD106 with or without adjuvant (Alum or MF59) in serum and CSF, e.g. by measuring Aß‐specific IgMs and Qß‐specific IgGs in serum, and markers of the quality of the immune response.; • To characterize Aß‐specific and Qß‐specific T‐cell response to CAD106 with or without adjuvant (Alum or MF59) using PBMCs.; • To evaluate changes over time of the concentrations of disease related markers (Aß1‐40 and Aß1‐42 in plasma; Aß1‐40, Aß1‐42, total‐tau, phospho‐tau in CSF, or other markers) in patients with mild AD receiving CAD106 with or without adjuvant (Alum or MF59) compared to placebo. Timepoint(s) of evaluation of this end point: 22 visits post baseline over 90 weeks (details see protocol table 6‐1).;