A phase II a , Multicenter, Randomized , Third -party Unblinded , Long- term Extension study to Determine Safety, Tolerability and Immunogenicity of ACC-001 with and without QS21 Adjuvant in Subjects with Mild to Moderate Alzheimzer's Disease

INTERVENTION: Product Name: ACC‐001 Product Code: ACC‐001 Pharmaceutical Form: Injection* Current Sponsor code: ACC‐001 Other descriptive name: A‐Beta‐1‐7‐CRM197 Conjugate Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 25‐ Product Name: ACC‐001 Product Code: ACC‐001 Pharmaceutical Form: Injection* Current Sponsor code: ACC‐001 Other descriptive name: A‐Beta‐1‐7‐CRM197 Conjugate Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 60‐ Product Name: ACC‐001 + QS‐21 Adjuvant Product Code: ACC‐001 + QS‐21 Adjuvant Pharmaceutical Form: Injection* Current Sponsor code: ACC‐001 Other descriptive name: A‐Beta‐1‐7‐CRM197 Conjugate Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 25‐ Product Name: ACC‐001 + QS‐21 Adjuvant Product Code: ACC‐001 + QS‐21 Adjuvant Pharmaceutical Form: Injection* Current Sponsor code: ACC‐001 Other descriptive name: A‐Beta‐1‐7‐CRM197 Conjugate Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 60‐ CONDITION: Patients with mild to moderate Alzheimer's disease. PRIMARY OUTCOME: Main Objective: The primary objective of the study is to evaluate the long‐term safety and tolerability of doses of 3, 10, and 30 µg of ACC‐001 (CRM‐conjugated A‐beta [1‐7] antigen alone and in combination with QS‐21 adjuvant) in subjects with mild to moderate AD. Primary end point(s): Safety assessments will include vital sign measurements, weight, physical and neurological examinations, 12‐lead ECG recordings, and brain MRI scans (at screening and before each immunization and at the end of the study), including T2*/gradient echo MRI). Clinical laboratory evaluations will include complete blood count (CBC) with platelet count, chemistry panel, and urinalysis, thyroid panel, serum vitamin B12 and folate, coagulation studies, and circulating immune complexes and anti‐A‐beta titers. Secondary Objective: • To assess the immunogenicity of doses of 3, 10, and 30 µg of ACC‐001; • To assess the long‐term efficacy of ACC‐001 in subjects with mild to moderate AD.; • To evaluate the effect of ACC‐001 on patient quality of life (QoL) and caregiver dependence and related health outcomes.; • To compare the efficacy at the end of the study between those subjects who received ACC‐001 with or without QS‐21 in the preceding double‐blind trial and those subjects who received phosphate‐buffered saline (PBS) or QS‐21 in the preceding trial.; • To evaluate the change from baseline volumes for whole brain volume, brain boundary shift integral (BBSI), ventricular volume, and ventricular boundary shift integral (BSI) as assessed from MRI scans.; INCLUSION CRITERIA: 1. Subjects were randomized under previous 3134K1‐200‐EU study and met all inclusion/and none of the exclusion criteria. 2. Subject must have completed through week 78 of study 3134K1‐200‐EU and received at least 3 doses of investigational product and has been compliant in the opinion of the investigator and sponsor. 3. Screening brain MRI scan is consistent with the diagnosis of AD. 4. Mini‐Mental State Examination (MMSE) score >10. 5. Lives at home with appropriate caregiver capable of accompanying the subject on all clinic visits, or community dwelling with caregiver capable of accompanying the subject on all clinic visits and visiting with the subject approximately 5 times per week for the duration of the study. 6. In the opinion of the investigator, the subject and the caregiver will be compliant and have a high probability of completing the study. 7. The subject and caregiver are likely to be able to participate in all scheduled examinati