Safety, Tolerability, And Immunogenicity Study Of ACC-001 In Japanese Subjects With Mild To Moderate Alzheimer's Disease

Safety, Tolerability, And Immunogenicity Study Of ACC-001 In Japanese Subjects With Mild To Moderate Alzheimer's Disease

Phase Iia, Multicenter, Randomized, Third-party Unblinded, Adjuvant-controlled, Multiple Ascending Dose, Safety, Tolerability, And Immunogenicity Trial Of Acc-001 Withqs-21 Adjuvant In Japanese Subjects With Mild To Moderate Alzheimer's Disease.

The purpose of this study is to assess the safety, tolerability, and immunogenicity of ACC-001, an investigational vaccine, in subjects with mild to moderate Alzheimer's disease in Japan.

Active vaccine + adjuvant, IM injection, dose of 3, 10 and 30 micrograms, at Day 1, month 1, 3, 6 and 12

Number of participants who experienced mild, moderate, or severe AEs (mild = does not interfere with subject's usual function; moderate = interferes to some extent with subject's usual function; severe = interferes significantly with subject's usual function)

Number of participants with brain abnormalities in MRI data that are either consistent or not consistent with AD, as determined by radiologists.

Number of participants with abnormalities in neurological examinations as determined by the investigators. Neurological examinations included Mental Status, Speech, Cranial Nerves (including pupil equality and reactivity), Visual field, Sensory, Motor, Coordination, Gait, Primitive reflexes, Tendon reflexes and Romberg.

The Mean Changes in Alzheimer's Disease Assessment Scale-Cognitive Behavior (ADAS-Cog) Score From Baseline at Week 12, 26, 52, 78 and 104.

The ADAS-Cog is a 12-item,objective measure of cognitive function, consisting of 1) Word Recall, 2) Naming Objects and Fingers, 3) Following Commands, 4) Constructional Praxis, 5) Ideational Praxis, 6) Orientation, 7) Word Recognition, 8) Recall of Test Instructions, 9) Spoken Language Ability, 10) Word-Finding Difficulty, 11) Comprehension of Spoken Language and 12) Concentration/Distractibility. For this study, the ADAS-Cog total score is derived by summing the individual scores from items 1 to 11. Total score ranges from 0 to 70 points, with higher scores indicating a greater degree of impairment.

The Mean Changes in Disability Assessment for Dementia (DAD) Score From Baseline at Week 12, 26, 52,78 and 104.

The DAD is administered through an interview with the caregiver and measures instrumental and basic activities of daily living. A total score is obtained by adding the rating for each question and converting this total score out of 100. Higher scores represent less disability in ADL while lower scores indicate more dysfunction.

The Mean Changes in Neuropsychological Test Battery (NTB) Score From Baseline at Week 12, 26, 52 and 78.

The NTB is a composite of nine widely used neuropsychological tests that assess immediate and delayed recall of verbal and visual information, attention, verbal fluency and executive function. The cognitive tests included in the NTB are the Wechsler Memory Scale (WMS) Visual-Paired Associates (immediate and delayed), WMS-Verbal Paired Associates (immediate and delayed), Rey Auditory Verbal Learning Test (immediate and delayed), WMS-Digit Span, Controlled Word Association Test, and Category Fluency Test. The NTB z-score is used for analysis. The z-score for each component is calculated through the following formula: z = (y_visit - y_base)/SD_base, where y_visit is a value at a particular time point and y_base is the average test score, and SD_base is the SD based on all participants' observed baseline scores in the study.

The Mean Changes in Mini-Mental State Examination (MMSE) Score From Baseline at Week 4, 8, 12, 16, 26, 30, 40, 52, 78 and 104.

The MMSE is a brief, structured examination of cognitive function. It has a total score of 30 points (0-30), and any score equal to or lower than 26 points indicates cognitive impairment.

Inclusion Criteria: Diagnosis of mild to moderate Alzheimer's Disease Mini-Mental State Examination (MMSE) 16-26 Exclusion Criteria: Significant Neurological Disease other than Alzheimer's disease Major psychiatric disorder Clinically significant systemic illness

Arai H, Suzuki H, Yoshiyama T. Vanutide cridificar and the QS-21 adjuvant in Japanese subjects with mild to moderate Alzheimer's disease: results from two phase 2 studies. Curr Alzheimer Res. 2015;12(3):242-54. doi: 10.2174/1567205012666150302154121.

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=3134K1-2206&StudyName=Safety%2C%20Tolerability%2C%20And%20Immunogenicity%20Study%20Of%20ACC-001%20In%20Japanese%20Subjects%20With%20Mild%20To%20Moderate%20Alzheimer%27s%20Disease