Safety, Tolerability, And Immunogenicity Study Of ACC-001 In Japanese Subjects With Mild To Moderate Alzheimer's Disease
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00959192
Collaborator
JANSSEN Alzheimer Immunotherapy Research & Development, LLC (Industry)
32
9
2
41
3.6
0.1
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
32 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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.
Study Start Date
:
Aug 1, 2009
Actual Primary Completion Date
:
Jan 1, 2013
Actual Study Completion Date
:
Jan 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ACC-001 + QS-21 Active vaccine + adjuvant, IM injection, dose of 3, 10 and 30 micrograms, at Day 1, month 1, 3, 6 and 12 |
Biological: ACC-001
IM injection, dose of 3, 10 and 30 micrograms, at Day 1, month 1, 3, 6 and 12
Other: QS-21
IM injection, dose of 50 micrograms, at Day 1, month 1, 3, 6 and 12
|
| Placebo Comparator: QS-21 Adjuvant, IM injection, dose 50 micrograms, at Day 1, month 1, 3, 6 and 12 |
Other: QS-21
IM injection, dose 50 micrograms, at Day 1, month 1, 3, 6 and 12
|
Outcome Measures
Primary Outcome Measures
- Incidence of Treatment-emergent Adverse Events (AEs) by Severity [Baseline up to 24 months]
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 Magnetic Resonance Imaging (MRI) Data [Baseline up to 24 months]
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 Examination [Baseline up to 24 months]
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.
Secondary Outcome Measures
- Anti-a-beta IgG Titer at Specified Visits [Baseline up to 24 months]
Geometric mean of anti-a-beta IgG titer from pre-study through Week 104
- Anti-a-beta IgM Titer at Specified Visits [Baseline up to 24 months]
Geotmetric mean of anti-a-beta IgM titer from pre-study through Week 104
Other Outcome Measures
- The Mean Changes in Alzheimer's Disease Assessment Scale-Cognitive Behavior (ADAS-Cog) Score From Baseline at Week 12, 26, 52, 78 and 104. [Baseline up to 24 months]
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. [Baseline up to 24 months]
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. [Baseline up to 24 months]
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. [Baseline up to 24 months]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
50 Years
to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Meitetsu Hospital | Aichi | Japan | 451-8511 | |
| 2 | Ibaraki Prefectural Central Hospital | Ibaraki | Japan | 309-1793 | |
| 3 | Shonan Atsugi Hospital | Kanagawa | Japan | 243-8551 | |
| 4 | Kitasato University East Hospital | Kanagawa | Japan | 252-0380 | |
| 5 | Tazuke Kofukai Medical Research Institute Kitano Hospital | Osaka | Japan | 530-8480 | |
| 6 | The Jikei University School of medicine | Tokyo | Japan | 105-8471 | |
| 7 | Juntendo University Hospital | Tokyo | Japan | 113-8431 | |
| 8 | Juntendo Tokyo Koto Geriatric Medical Center | Tokyo | Japan | 136-0075 | |
| 9 | Kanto Ctrl Hp of the Mutual Aid Asso of Public school Teache | Tokyo | Japan | 158-8531 |
Sponsors and Collaborators
- Pfizer
- JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00959192
Other Study ID Numbers:
- 3134K1-2206
- B2571009
First Posted:
Aug 14, 2009
Last Update Posted:
Jan 1, 2016
Last Verified:
Nov 1, 2015
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 |
|---|---|---|---|---|
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 |
| Period Title: Overall Study | ||||
| STARTED | 6 | 9 | 9 | 8 |
| COMPLETED | 4 | 8 | 6 | 7 |
| NOT COMPLETED | 2 | 1 | 3 | 1 |
Baseline Characteristics
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 | Total |
|---|---|---|---|---|---|
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | Total of all reporting groups |
| Overall Participants | 6 | 9 | 9 | 8 | 32 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
72.50
(8.73)
|
68.00
(10.34)
|
74.33
(6.69)
|
64.75
(7.15)
|
69.81
(8.83)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
6
100%
|
6
66.7%
|
6
66.7%
|
7
87.5%
|
25
78.1%
|
| Male |
0
0%
|
3
33.3%
|
3
33.3%
|
1
12.5%
|
7
21.9%
|
Outcome Measures
| Title | Incidence of Treatment-emergent Adverse Events (AEs) by Severity |
|---|---|
| Description | 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) |
| Time Frame | Baseline up to 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis population includes all of the randomly assigned participants who took at least one dose of study medication. |
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 |
|---|---|---|---|---|
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 |
| Measure Participants | 6 | 9 | 9 | 8 |
| Mild |
4
66.7%
|
7
77.8%
|
7
77.8%
|
5
62.5%
|
| Moderate |
2
33.3%
|
1
11.1%
|
1
11.1%
|
2
25%
|
| Severe |
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
| Title | Number of Participants With Brain Abnormalities in Magnetic Resonance Imaging (MRI) Data |
|---|---|
| Description | Number of participants with brain abnormalities in MRI data that are either consistent or not consistent with AD, as determined by radiologists. |
| Time Frame | Baseline up to 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis population includes all of the randomly assigned participants who took at least one dose of study medication. |
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 |
|---|---|---|---|---|
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 3, 6, 9 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 |
| Measure Participants | 6 | 9 | 9 | 8 |
| Abnormal - inconsistent with AD |
1
16.7%
|
0
0%
|
2
22.2%
|
0
0%
|
| Abnormal - consistent with AD |
6
100%
|
9
100%
|
9
100%
|
8
100%
|
| Title | Number of Participants With Abnormalities in Neurological Examination |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis population includes all of the randomly assigned participants who took at least one dose of study medication. |
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 |
|---|---|---|---|---|
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 3, 6, 9 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 |
| Measure Participants | 6 | 9 | 9 | 8 |
| Total |
1
16.7%
|
1
11.1%
|
0
0%
|
0
0%
|
| Mental Status |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Speech |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Cranial Nerves |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Visual Field |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sensory |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
| Motor |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Coordination |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Gate |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Primitive reflexes |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Tendon reflexes |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Romberg |
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
| Title | Anti-a-beta IgG Titer at Specified Visits |
|---|---|
| Description | Geometric mean of anti-a-beta IgG titer from pre-study through Week 104 |
| Time Frame | Baseline up to 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population for immunogenicity analysis includes all of the randomly assigned participants who took at least one dose of study medication, having the baseline and at least one post baseline immunogenicity evaluation. |
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 |
|---|---|---|---|---|
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 |
| Measure Participants | 6 | 9 | 9 | 8 |
| Pre-study (n=6,9,9,8) |
50.0
|
50.0
|
50.0
|
50.0
|
| Week 2 (n=6,9,9,8) |
62.2
|
65.0
|
67.0
|
50.0
|
| Week 4 (n=6,9,9,8) |
107.9
|
94.2
|
79.0
|
50.0
|
| Week 6 (n=6,9,9,8) |
2106.5
|
4793.2
|
5702.6
|
50.0
|
| Week 8 (n=6,9,9,8) |
1143.3
|
2331.4
|
3423.9
|
50.0
|
| Week 10 (n=6,9,9,8) |
979.2
|
1674.9
|
2012.4
|
50.0
|
| Week 14 (n=6,9,9,8) |
6088.4
|
6286.2
|
9983.5
|
50.0
|
| Week 16 (n=6,9,9,8) |
3860.4
|
4170.4
|
9228.0
|
50.0
|
| Week 24 (n=6,9,9,8) |
1151.5
|
1455.0
|
3903.1
|
50.0
|
| Week 28 (n=6,9,7,8) |
8216.5
|
8929.3
|
7429.5
|
50.0
|
| Week 30 (n=6,9,7,8) |
7218.7
|
7017.4
|
6162.2
|
50.0
|
| Week 40 (n=5,9,8,8) |
3136.4
|
2706.5
|
3615.5
|
50.0
|
| Week 50 (n=6,8,7,8) |
1854.5
|
1255.8
|
1261.4
|
50.0
|
| Week 54 (n=5,8,7,7) |
2873.6
|
9636.4
|
8604.6
|
50.0
|
| Week 56 (n=4,8,7,7) |
11006.2
|
7582.4
|
6201.5
|
50.0
|
| Week 66 (n=4,8,7,7) |
7407.9
|
3942.5
|
2452.5
|
50.0
|
| Week 78 (n=4,8,6,7) |
5108.6
|
2465.3
|
1316.3
|
50.0
|
| Week 91 (n=0,1,1,0) |
NA
|
546.0
|
389.0
|
NA
|
| Week 104 (n=0,1,1,0) |
NA
|
414.0
|
285.0
|
NA
|
| Title | Anti-a-beta IgM Titer at Specified Visits |
|---|---|
| Description | Geotmetric mean of anti-a-beta IgM titer from pre-study through Week 104 |
| Time Frame | Baseline up to 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population for immunogenicity analysis includes all of the randomly assigned participants who took at least one dose of study medication, having the baseline and at least one post baseline immunogenicity evaluation. |
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 |
|---|---|---|---|---|
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 3, 6, 9 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 |
| Measure Participants | 6 | 9 | 9 | 8 |
| Pre-study (n=6,9,9,8) |
30.9
|
28.2
|
25.0
|
41.5
|
| Week 2 (n=6,9,9,8) |
77.1
|
92.0
|
53.5
|
42.4
|
| Week 4 (n=6,9,9,8) |
108.5
|
141.5
|
108.5
|
43.7
|
| Week 6 (n=6,9,9,8) |
953.2
|
2988.4
|
2381.4
|
43.0
|
| Week 8 (n=6,9,9,8) |
848.6
|
2940.1
|
2776.2
|
46.9
|
| Week 10 (n=6,9,9,8) |
850.8
|
2432.1
|
2323.9
|
36.1
|
| Week 14 (n=6,9,9,8) |
1487.6
|
2231.0
|
4438.5
|
37.6
|
| Week 16 (n=6,9,9,8) |
1503.2
|
2484.8
|
4590.6
|
40.5
|
| Week 24 (n=6,9,9,8) |
898.5
|
1421.8
|
2396.4
|
40.1
|
| Week 28 (n=6,9,7,8) |
885.9
|
3395.8
|
3592.8
|
42.1
|
| Week 30 (n=6,9,7,8) |
859.5
|
3729.9
|
2956.7
|
38.9
|
| Week 40 (n=5,9,8,8) |
449.0
|
2480.5
|
1967.3
|
37.8
|
| Week 50 (n=6,8,7,8) |
354.2
|
1330.0
|
1326.8
|
39.9
|
| Week 54 (n=5,8,7,7) |
680.7
|
2605.4
|
3017.0
|
48.3
|
| Week 56 (n=4,8,7,7) |
1768.3
|
2570.6
|
3051.9
|
40.5
|
| Week 66 (n=4,8,7,7) |
1213.0
|
1872.7
|
1825.1
|
46.0
|
| Week 78 (n=4,8,6,7) |
952.8
|
1650.3
|
844.9
|
48.3
|
| Week 91 (n=0,1,1,0) |
NA
|
219.0
|
351.0
|
NA
|
| Week 104 (n=0,1,1,0) |
NA
|
154.0
|
258.0
|
NA
|
| Title | The Mean Changes in Alzheimer's Disease Assessment Scale-Cognitive Behavior (ADAS-Cog) Score From Baseline at Week 12, 26, 52, 78 and 104. |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy analyses were performed on the modified intent-to-treat (mITT) population. The mITT population included all of the randomly assigned participants who took at least one dose of study medication, and had the baseline and at least one post baseline evaluation of the key efficacy variable (ADAS-Cog). |
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 |
|---|---|---|---|---|
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 |
| Measure Participants | 6 | 9 | 9 | 8 |
| Week 12 (n=6,9,9,8) |
0.06
(5.20)
|
0.52
(4.39)
|
2.93
(4.10)
|
-0.25
(3.30)
|
| Week 26 (n=6,9,9,8) |
0.39
(4.38)
|
-0.41
(5.41)
|
3.56
(6.74)
|
-0.63
(5.76)
|
| Week 52 (n=5,9,7,8) |
1.87
(8.32)
|
0.15
(4.82)
|
5.05
(6.68)
|
1.04
(7.01)
|
| Week 78 (n=4,8,6,7) |
0.17
(3.50)
|
3.40
(7.08)
|
5.39
(3.66)
|
2.33
(7.78)
|
| Week 104 (n=0,1,1,0) |
NA
(NA)
|
-4.33
(NA)
|
8.33
(NA)
|
NA
(NA)
|
| Title | The Mean Changes in Disability Assessment for Dementia (DAD) Score From Baseline at Week 12, 26, 52,78 and 104. |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy analyses were performed on the modified intent-to-treat (mITT) population. The mITT population included all of the randomly assigned participants who took at least one dose of study medication, and had the baseline and at least one post baseline evaluation of the key efficacy variable (ADAS-Cog). |
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 |
|---|---|---|---|---|
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 3, 6, 9 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 |
| Measure Participants | 6 | 9 | 8 | 8 |
| Week 12 (n=5,9,7,8) |
-4.7
(9.7)
|
0.7
(2.6)
|
1.5
(5.1)
|
1.7
(6.4)
|
| Week 26 (n=6,9,8,8) |
-10.1
(14.5)
|
-0.2
(11.9)
|
-4.4
(28.6)
|
-0.6
(6.5)
|
| Week 52 (n=5,8,6,8) |
-11.2
(20.9)
|
-3.4
(10.7)
|
-1.8
(5.1)
|
-3.1
(9.0)
|
| Week 78 (n=4,8,5,6) |
-0.6
(3.1)
|
-5.4
(7.7)
|
0.5
(6.9)
|
3.5
(3.2)
|
| Week 104 (n=0,1,1,0) |
NA
(NA)
|
0
(NA)
|
12.8
(NA)
|
NA
(NA)
|
| Title | The Mean Changes in Neuropsychological Test Battery (NTB) Score From Baseline at Week 12, 26, 52 and 78. |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy analyses were performed on the modified intent-to-treat (mITT) population. The mITT population included all of the randomly assigned participants who took at least one dose of study medication, and had the baseline and at least one post baseline evaluation of the key efficacy variable (ADAS-Cog). |
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 |
|---|---|---|---|---|
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 3, 6, 9 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 |
| Measure Participants | 6 | 9 | 9 | 8 |
| Week 12 (n=6,9,8,8) |
0.023
(0.416)
|
0.275
(0.280)
|
-0.028
(0.282)
|
0.227
(0.107)
|
| Week 26 (n=6,9,9,8) |
0.114
(0.423)
|
0.254
(0.353)
|
-0.081
(0.530)
|
0.222
(0.308)
|
| Week 52 (n=5,9,7,8) |
0.081
(0.288)
|
0.211
(0.285)
|
-0.109
(0.263)
|
0.213
(0.416)
|
| Week 78 (n=4,8,6,7) |
-0.088
(0.334)
|
-0.037
(0.494)
|
-0.120
(0.442)
|
0.246
(0.336)
|
| Week 104 (n=0,1,1,0) |
NA
(NA)
|
0.514
(NA)
|
-0.559
(NA)
|
NA
(NA)
|
| Title | 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. |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy analyses were performed on the modified intent-to-treat (mITT) population. The mITT population included all of the randomly assigned participants who took at least one dose of study medication, and had the baseline and at least one post baseline evaluation of the key efficacy variable (ADAS-Cog). |
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 |
|---|---|---|---|---|
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 3, 6, 9 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 |
| Measure Participants | 6 | 9 | 9 | 8 |
| Week 4 (n=6,9,9,8) |
1.7
(1.5)
|
1.3
(1.7)
|
1.6
(2.7)
|
0.4
(2.3)
|
| Week 8 (n=6,9,9,8) |
2.2
(3.1)
|
0.9
(3.2)
|
1.3
(1.7)
|
0.9
(2.6)
|
| Week 12 (n=6,9,9,8) |
0.8
(2.8)
|
1.1
(2.7)
|
1.1
(2.0)
|
1.4
(2.7)
|
| Week 16 (n=6,9,9,8) |
1.5
(3.4)
|
1.3
(2.3)
|
2.9
(2.5)
|
0.4
(1.8)
|
| Week 26 (n=6,9,8,8) |
0.3
(3.8)
|
0.1
(2.6)
|
1.0
(2.8)
|
-0.1
(1.6)
|
| Week 30 (n=6,9,8,8) |
0.3
(3.7)
|
1.2
(2.4)
|
1.6
(2.4)
|
0.3
(3.3)
|
| Week 40 (n=4,9,7,8) |
2.3
(2.2)
|
0.8
(3.5)
|
0.7
(2.0)
|
0.5
(3.2)
|
| Week 52 (n=5,8,7,7) |
0.4
(4.5)
|
1.0
(3.8)
|
1.1
(2.1)
|
0.6
(2.5)
|
| Week 78 (n=4,8,6,7) |
1.8
(2.5)
|
-1.4
(3.9)
|
-0.3
(1.2)
|
0.0
(3.2)
|
| Week 104 (n=0,1,1,0) |
NA
(NA)
|
-2.0
(NA)
|
-1.0
(NA)
|
NA
(NA)
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. | |||||||
| Arm/Group Title | ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 | ||||
| Arm/Group Description | A cohort of participants who received intramuscular (IM) injection of active vaccine ACC-001 (3 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (10 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of active vaccine ACC-001 (30 micrograms) + adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | A cohort of participants who received IM injection of adjuvant QS-21 (50 micrograms) at Day 1, month 1, 3, 6 and 12 | ||||
All Cause Mortality |
||||||||
| ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| ACC-001 3 Micrograms + QS-21 | ACC-001 10 Micrograms + QS-21 | ACC-001 30 Micrograms + QS-21 | QS-21 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 8/9 (88.9%) | 9/9 (100%) | 7/8 (87.5%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Iron deficiency anaemia | 0/6 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Vestibular disorder | 0/6 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | ||||
| Gastrointestinal disorders | ||||||||
| Constipation | 1/6 (16.7%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Dental caries | 0/6 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | ||||
| Gastric ulcer | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Nausea | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Vomiting | 1/6 (16.7%) | 1/9 (11.1%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| General disorders | ||||||||
| Injection site erythema | 2/6 (33.3%) | 1/9 (11.1%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Injection site haematoma | 0/6 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | ||||
| Injection site pain | 1/6 (16.7%) | 0/9 (0%) | 1/9 (11.1%) | 2/8 (25%) | ||||
| Injection site swelling | 3/6 (50%) | 1/9 (11.1%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Pyrexia | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Immune system disorders | ||||||||
| Food allergy | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Infections and infestations | ||||||||
| Cellulitis | 0/6 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Enterocolitis infectious | 0/6 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | ||||
| Folliculitis | 0/6 (0%) | 1/9 (11.1%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Gastroenteritis viral | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Gingivitis | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Herpes zoster | 0/6 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | ||||
| Influenza | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Nasopharyngitis | 2/6 (33.3%) | 4/9 (44.4%) | 3/9 (33.3%) | 3/8 (37.5%) | ||||
| Periodontitis | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Pharyngitis | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Chillblains | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Contusion | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Fall | 1/6 (16.7%) | 2/9 (22.2%) | 0/9 (0%) | 1/8 (12.5%) | ||||
| Head injury | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Ligament sprain | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Spinal compression fracture | 1/6 (16.7%) | 1/9 (11.1%) | 0/9 (0%) | 1/8 (12.5%) | ||||
| Subcutaneous haematoma | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Subdural haematoma | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Wrist fracture | 0/6 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | ||||
| Investigations | ||||||||
| Aspartate aminotransferase increased | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Blood alkaline phosphatase increased | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Blood cholesterol increased | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Blood creatine phosphokinase increased | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Blood pressure decreased | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Electrocardiogram QT prolonged | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Gamma-glutamyltransferase increased | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Positive Rombergism | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Protein urine present | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/6 (16.7%) | 0/9 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | ||||
| Dehydration | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Lipid metabolism disorder | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Musculoskeletal chest pain | 0/6 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Osteoporosis | 1/6 (16.7%) | 1/9 (11.1%) | 0/9 (0%) | 1/8 (12.5%) | ||||
| Spinal osteoarthritis | 0/6 (0%) | 2/9 (22.2%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Nervous system disorders | ||||||||
| Cerebral infarction | 0/6 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Cerebral microhaemorrhage | 0/6 (0%) | 0/9 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | ||||
| Dizziness | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Dyskinesia | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Haemorrhagic cerebral infarction | 0/6 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Headache | 0/6 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Hypoaesthesia | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Intercostal neuralgia | 0/6 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Loss of consciousness | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Meralgia paraesthetica | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Psychiatric disorders | ||||||||
| Agitation | 0/6 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Anxiety | 0/6 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | ||||
| Depression | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Haemorrhage subcutaneous | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Rash pruritic | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
| Urticaria | 1/6 (16.7%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/6 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00959192
Other Study ID Numbers:
- 3134K1-2206
- B2571009
First Posted:
Aug 14, 2009
Last Update Posted:
Jan 1, 2016
Last Verified:
Nov 1, 2015