P1–338: Safety, Tolerability and Immunogenicity of an Immunotherapeutic Vaccine (vanutide Cridificar [ACC‐001]) and the QS‐21 Adjuvant in Japanese Individuals with Mild‐to‐moderate Alzheimer's Disease: A Phase IIa, Multicenter, Randomized, Adjuvant and Placebo Clinical Trial

Vanutide cridificar (ACC-001) is a novel immunotherapeutic vaccine for the treatment of Alzheimer's Disease (AD) composed of amino-terminal peptides (1–7) of amyloid beta (Aβ) conjugated to a CRM 197 carrier, designed to elicit an anti-Aβ antibody response while avoiding an Aβ(1–42)-directed T-cell response. Objective: To assess the safety and tolerability of multiple doses of ACC-001 in Japanese subjects with mild to moderate AD. Immunogenicity and exploratory efficacy assessments were also conducted. Subjects were treated with 3μg of ACC-001 with QS-21 adjuvant (50μg), 10μg or 30μg of ACC-001 with/without QS-21, QS-21 alone, or PBS alone at day 1 and months 3, 6, 9, and 12, and followed for 12 months. Immunogenicity was evaluated by anti-Aβ IgG antibody titration. Exploratory efficacy evaluations included ADAS-Cog, DAD, NTB, and MMSE. Forty subjects were randomized and treated with either QS-21 50μg alone; 3μg, 10μg, or 30μg of ACC-001 with/without QS-21 (n=6 for each group); or PBS (n=4). Thirty-two subjects (80%) completed the study and 8 subjects (20%) discontinued the study for reasons other than adverse events (AEs) or lack of efficacy. The most common (≥2 subjects) treatment-emergent AEs (TEAEs) in the ACC-001 with/without QS-21 group were cataract, dental caries, injection site erythema/pain, pyrexia, nasopharyngitis, contusion, blood triglycerides increased, glucosuria, proteinuria, and back pain. Most TEAEs were mild (32 subjects) or moderate (3) in severity and self-limiting. Serious AEs were reported for 2 subjects: contusion, cholecystitis infective, and duodenal ulcer (ACC-001 3μg + QS-21, considered not related to study drug) and angina pectoris (ACC-001 30μg + QS-21, considered treatment related). No deaths occurred. High titer and sustained anti-Aβ IgG antibodies were observed in the ACC-001 with QS-21 groups. Addition of QS-21 was essential for high-titer responses. Due to a small number of subjects and intersubject variability, exploratory efficacy results did not support or refute a clinical benefit with ACC-001. Repeat administration of ACC-001 (3μg, 10μg, and 30μg) with/without QS-21 was generally safe and well tolerated. Addition of QS-21 was essential to elicit high-titer responses. High-titer, sustained, anti-Aβ IgG responses were observed with no apparent differences among the 3 ACC-001 doses tested.