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

A Phase Iia, Multicenter, Treatment Assigned, Open-label, Long-term Extension Study To Determine Safety, Tolerability, And Immunogenicity Of Acc-001 With Qs-21 Adjuvant In Japanese Subjects With Mild To Moderate Alzheimer's Disease

The purpose of this long term extension study is to assess safety, tolerability and immunogenicity of ACC-001 with QS-21 adjuvant in Japanese subjects with mild to moderate AD who were randomized in the preceding P2 double blind studies.

Study Overview

• Status: Terminated
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Biological: ACC-001; Biological: ACC-001; Biological: ACC-001

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 530-8480
    • Tazuke Kofukai Medical Research Institute Kitano Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 451-8511
      • Meitetsu Hospital
  • Ibaraki
    • Kasama, Ibaraki, Japan, 309-1793
      • Ibaraki Prefectural Central Hospital
  • Kanagawa
    • Atsugi, Kanagawa, Japan, 243-8551
      • Shonan Atsugi Hospital
    • Sagamihara-shi, Kanagawa, Japan, 252-0380
      • Kitasato University East Hospital
  • Nagano
    • Suwa, Nagano, Japan, 392-8510
      • Suwa Red Cross Hospital
  • Osaka
    • Takatsuki, Osaka, Japan, 569-8686
      • Osaka Medical College Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital
    • Koto-ku, Tokyo, Japan, 136-0075
      • Juntendo Tokyo Koto Geriatric Medical Center
    • Minato-ku, Tokyo, Japan, 105-8471
      • The Tokyo Jikei University School of Medicine
    • Setagaya-ku, Tokyo, Japan, 158-8531
      • Kanto Central Hospital of the Mutual Aid Association of Public School Teachers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 52 years to 87 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects randomized under previous 3134K1-2202-JA (NCT00752232) and 3134K1-2206-JA (NCT00959192) and met all inclusion criteria and non of the exclusion criteria.
• Screening brain MRI scan is consistent with the diagnosis of AD.
• MMSE score 10 and above.

Exclusion Criteria:

• Significant neurological diseases other than AD.
• Brain MRI evidence of vasogenic edema during the preceding studies.
• Clinically significant illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACC-001 (3 micrograms) + QS-21; Active vaccine dose of 3 micrograms +adjuvant, IM injection, at Day 1, month 6, 12 and 18	Biological: ACC-001; IM injection, dose of 3 micrograms, at Day 1, month 6, 12 and 18; Biological: ACC-001; IM injection, dose of 10 micrograms, at Day 1, month 6, 12 and 18; Biological: ACC-001; IM injection, dose of 30 micrograms, at Day 1, month 6, 12 and 18
Experimental: ACC-001 (10 micrograms) + QS-21; Active vaccine dose of 10 micrograms +adjuvant, IM injection, at Day 1, month 6, 12 and 18	Biological: ACC-001; IM injection, dose of 3 micrograms, at Day 1, month 6, 12 and 18; Biological: ACC-001; IM injection, dose of 10 micrograms, at Day 1, month 6, 12 and 18; Biological: ACC-001; IM injection, dose of 30 micrograms, at Day 1, month 6, 12 and 18
Experimental: ACC-001 (30 micrograms) + QS-21; Active vaccine dose of 30 micrograms +adjuvant, IM injection, at Day 1, month 6, 12 and 18	Biological: ACC-001; IM injection, dose of 3 micrograms, at Day 1, month 6, 12 and 18; Biological: ACC-001; IM injection, dose of 10 micrograms, at Day 1, month 6, 12 and 18; Biological: ACC-001; IM injection, dose of 30 micrograms, at Day 1, month 6, 12 and 18

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Emergent Adverse Events (AEs) by Severity	Number of mild, moderate, and 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)	Baseline up to 24 months
Number of Participants With Brain Abnormalities in Magnetic Resonance Imaging (MRI) Data	Number of participants with brain abnormalities in MRI data that are either consistent or not consistent with AD, as determined by radiologists.	Baseline up to 24 months
Number of Participants With Abnormalities in Neurological Examination	Number of participants with abnormalities in neurological examinations as determined by the investigators. Neurological examinations included Mental Status, Speech, Cranial Nerve Function, Cranial Nerve II, Sensory Function, Motor Function, Coordination, Gait and Station, Reflexes and Deep Tendon Reflexes.	Baseline of the preceding studies through 24 months of this study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-A-beta IgG (Immunoglobulin G) Titer at Specified Visits	Geometric mean of anti-a-beta IgG titer from baseline of the preceding studies through the end of this study	Baseline of preceding studies to month 24 of this study (Week 210)
Anti-A-beta IgM (Immunoglobulin M) Titer at Specified Visits	Geotmetric mean of anti-a-beta IgM titer from baseline of the preceding studies through the end of this study	Baseline of preceding studies to month 24 of this study (Week 210)
The Mean Changes in Alzheimer's Disease Assessment Scale-Cognitive Behavior (ADAS-Cog) Score From Baseline at Week 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, with higher scores indicating a greater degree of impairment. The total score ranges from 0 (no impairment) to 70 (worst impairment).	Baseline up to 24 Months
The Mean Changes in Disability Assessment for Dementia (DAD) Score From Baseline at Week 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.	Baseline up to 24 Months
The Mean Changes in Neuropsychological Test Battery (NTB) Score From Baseline at Week 26, 52, 78 and 104.	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.	Baseline up to 24 Months
The Mean Changes in Mini-Mental State Examination (MMSE) Score From Baseline at Week 12, 26, 36, 52, 66, 78, 91 and 104.	The MMSE is a brief, structured examination of cognitive function. It has a total score of 30 points, and any score equal to or lower than 26 points indicates cognitive impairment.	Baseline up to 24 Months

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: JANSSEN Alzheimer Immunotherapy Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: October 21, 2010
• First Submitted That Met QC Criteria: November 9, 2010
• First Posted (Estimate): November 11, 2010

Study Record Updates

• Last Update Posted (Estimate): December 22, 2014
• Last Update Submitted That Met QC Criteria: December 12, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: B2571001; 3134K1-2207 (Other Identifier: Alias Study Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No