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

This study has been completed.
Sponsor:
Collaborator:
Janssen Alzheimer Immunotherapy (JAI) Research and Development, LLC
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00479557
First received: May 24, 2007
Last updated: November 30, 2015
Last verified: November 2015
Results First Received: May 6, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer Disease
Interventions: Biological: ACC-001 + QS-21
Biological: ACC-001
Biological: QS-21
Drug: Placebo: Phosphate buffered saline

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Planned duration was approximately 110 weeks (including 6 week screening period, 52 weeks of dosing, and 52 weeks of follow-up). Participants who completed the 3134K1-200-EU (B2571004) study through Week 78 had the option to exit after this time point, for continued treatment and follow-up under extension protocol 3134K1-2203-EU (B2571007).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The Basic Results disclose pooled data from studies NCT00479557 and NCT00498602.

Reporting Groups
  Description
ACC 3 µg+QS-21 Participants received 3 µg of ACC-001 and 50 µg of QS-21. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
ACC 10 µg+QS-21 Participants received 10 µg of ACC-001 and 50 µg of QS-21. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
ACC 30 µg+QS-21 Participants received 30 µg of ACC-001 and 50 µg of QS-21. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
ACC 10 µg Participants received 10 µg of ACC-001. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
ACC 30 µg Participants received 30 µg of ACC-001. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
QS-21 Alone Participants received 50 µg of QS-21. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
Phosphate Buffered Saline Participants received Phosphate buffered Saline (PBS). Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.

Participant Flow:   Overall Study
    ACC 3 µg+QS-21     ACC 10 µg+QS-21     ACC 30 µg+QS-21     ACC 10 µg     ACC 30 µg     QS-21 Alone     Phosphate Buffered Saline  
STARTED     36     61     40     35     12     44     17  
Treated     36     60 [1]   40     35     12     44     17  
COMPLETED     26     51     32     30     8     31     15  
NOT COMPLETED     10     10     8     5     4     13     2  
Death                 0                 0                 0                 0                 0                 1                 0  
Lack of Efficacy                 1                 0                 0                 0                 0                 0                 0  
Lost to Follow-up                 0                 2                 0                 2                 0                 0                 0  
Adverse Event (AE) related to Study Drug                 1                 0                 3                 2                 0                 1                 0  
AE not related to Study Drug                 1                 3                 0                 0                 2                 2                 1  
Caregiver Request                 2                 2                 2                 0                 1                 2                 0  
Investigator Request                 0                 0                 1                 0                 0                 0                 0  
Subject Request                 3                 0                 1                 1                 1                 4                 1  
Not specified                 2                 3                 1                 0                 0                 3                 0  
[1] One participant discontinued due to an AE, with an outcome of death.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
245 participants were randomized in both studies (86 participants in 3134K1-200-EU [B2571004] and 159 participants in 3134K1-2201-US [B2571005]) and included in the analysis below. One participant of the randomized participants did not receive treatment.

Reporting Groups
  Description
ACC 3 µg+QS-21 Participants received 3 µg of ACC-001 and 50 µg of QS-21. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
ACC 10 µg+QS-21 Participants received 10 µg of ACC-001 and 50 µg of QS-21. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
ACC 30 µg+QS-21 Participants received 30 µg of ACC-001 and 50 µg of QS-21. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
ACC 10 µg Participants received 10 µg of ACC-001. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
ACC 30 µg Participants received 30 µg of ACC-001. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
QS-21 Alone Participants received 50 µg of QS-21. Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
Phosphate Buffered Saline Participants received Phosphate buffered Saline (PBS). Test article was given by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, and 12 months.
Total Total of all reporting groups

Baseline Measures
    ACC 3 µg+QS-21     ACC 10 µg+QS-21     ACC 30 µg+QS-21     ACC 10 µg     ACC 30 µg     QS-21 Alone     Phosphate Buffered Saline     Total  
Number of Participants  
[units: participants]
  36     61     40     35     12     44     17     245  
Age  
[units: year]
Mean (Standard Deviation)
  65.7  (7.75)     69.3  (9.57)     69.0  (9.27)     71.9  (8.96)     70.9  (9.59)     68.8  (8.07)     69.4  (7.82)     69.1  (8.87)  
Gender  
[units: number of participants]
               
Female     16     29     22     19     8     31     14     139  
Male     20     32     18     16     4     13     3     106  
Race/Ethnicity, Customized  
[units: number of participants]
               
Asian     0     0     0     0     1     0     0     1  
Black or African American     1     0     1     0     0     1     0     3  
Other     2     1     1     1     0     0     0     5  
White     33     60     38     34     11     43     17     236  
Mini-Mental State Examination (MMSE) Score [1]
[units: score]
Mean (Standard Deviation)
  21.4  (2.96)     21.4  (3.38)     21.0  (2.92)     21.6  (3.16)     21.8  (3.60)     21.7  (3.11)     21.2  (3.17)     21.4  (3.13)  
MMSE Stratum [1]
[units: number of participants]
               
High (21 - 26)     26     40     24     23     8     29     11     161  
Low (16 - 20)     10     21     16     12     4     15     6     84  
[1] The MMSE was used to systematically and thoroughly assess mental status of participants. It is an 11-question measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. The total score ranges from 0 to 30. A score of 23 or lower is indicative of cognitive impairment.



  Outcome Measures
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1.  Primary:   Percentage of Participants With Treatment-emergent AEs or Serious Adverse Events (SAEs)   [ Time Frame: approximately 110 weeks, including a 6-week screening period, 52 weeks of dosing and 54 weeks for follow-up after the last dose. ]

2.  Secondary:   Geometric Mean Titers (GMTs) of Anti-A-beta Immunoglobulin G (IgG) Total Using an Enzyme-linked Immunosorbent Assay (ELISA) at Weeks 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104   [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 ]

3.  Secondary:   GMTs of Anti-A-beta Immunoglobulin M (IgM) Using ELISA at Weeks 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104   [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 ]

4.  Secondary:   Change From Baseline GMTs of Anti-A-beta IgG Subtypes Using ELISA at Visits Where an IgG Total Response is Measurable (at Weeks 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 if Applicable)   [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com



Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00479557     History of Changes
Other Study ID Numbers: 3134K1-200
B2571004 ( Other Identifier: Alias Study Number )
2006-002061-39 ( EudraCT Number )
Study First Received: May 24, 2007
Results First Received: May 6, 2014
Last Updated: November 30, 2015
Health Authority: European Union: European Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Spain: Ministry of Health