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A Long Term Extension Study Evaluating ACC-001 With QS-21 in Subjects With Mild to Moderate Alzheimer's Disease

This study has been terminated.
Sponsor:
Collaborator:
JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00960531
First received: August 13, 2009
Last updated: March 2, 2016
Last verified: March 2016
Results First Received: December 18, 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+ QS21 (3mcg)
Biological: ACC-001 (10 mcg) + QS-21
Biological: ACC-001+QS-21 (30mcg)

  Participant Flow
  Hide Participant Flow

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 2 years (including 18 months of treatment + 6 months of follow-up). Participants who completed lead-in B2571005 study through Week 78 had the option to stay in the lead-in study, or to roll-over into the extension protocol B2571008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
ACC 3 µg+QS-21 / ACC 3 µg+QS-21 Participants received 3 μg of ACC-001 and 50 μg of QS-21 in the lead-in study and in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
QS-21 / ACC 3 µg+QS-21 Participants received 50 μg of QS-21 in the lead-in study and 3 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
ACC 10 µg+QS-21 / ACC 10 µg+QS-21 Participants received 10 μg of ACC-001 and 50 μg of QS-21 in the lead-in study and in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
ACC 10 µg / ACC 10 µg+QS-21 Participants received 10 μg of ACC-001 in the lead-in study and 10 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
QS-21 / ACC 10 µg+QS-21 Participants received 50 μg of QS-21 in the lead-in study and 10 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
PBS / ACC 10 µg+QS-21 Participants received Phosphate buffered Saline (PBS) in the lead-in study and 10 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
ACC 30 µg+QS-21 / ACC 30 µg+QS-21 Participants received 30 μg of ACC-001 and 50 μg of QS-21 in the lead-in study and in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
ACC 30 µg / ACC 30 µg+QS-21 Participants received 30 μg of ACC-001 in the lead-in study and 30 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
QS-21 / ACC 30 µg+QS-21 Participants received 50 μg of QS-21 in the lead-in study and 30 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
PBS / ACC 30 μg+QS-21 Participants received PBS in the lead-in study and 30 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.

Participant Flow:   Overall Study
    ACC 3 µg+QS-21 / ACC 3 µg+QS-21   QS-21 / ACC 3 µg+QS-21   ACC 10 µg+QS-21 / ACC 10 µg+QS-21   ACC 10 µg / ACC 10 µg+QS-21   QS-21 / ACC 10 µg+QS-21   PBS / ACC 10 µg+QS-21   ACC 30 µg+QS-21 / ACC 30 µg+QS-21   ACC 30 µg / ACC 30 µg+QS-21   QS-21 / ACC 30 µg+QS-21   PBS / ACC 30 μg+QS-21
STARTED   21 [1]   6 [1]   41 [1]   25 [2]   5 [1]   9 [1]   27 [1]   6 [1]   16 [1]   4 [1] 
Treated   21   6   41   24   5   9   27   6   16   4 
Completed Treatment   12   5   15   17   3   7   4   3   2   4 
COMPLETED   11 [3]   5 [3]   15 [3]   17 [3]   3 [3]   6 [3]   3 [3]   2 [3]   2 [3]   3 [3] 
NOT COMPLETED   10   1   26   8   2   3   24   4   14   1 
Lack of Efficacy                1                0                0                0                0                0                0                0                0                0 
Withdrawal by Subject                1                0                5                2                0                0                2                0                1                0 
Caregiver Request                2                0                6                5                0                2                3                1                3                0 
Investigator Request                0                0                1                0                0                0                0                0                0                0 
Discontinuation of Study by Sponsor                0                0                0                0                0                0                0                1                0                0 
Lost to Follow-up                0                0                1                0                0                0                1                0                0                0 
Failed to Return                2                0                0                0                0                0                0                2                0                0 
Adverse Event (AE)                2                0                0                0                0                1                2                0                2                0 
Reason not Specified                2                1                13                1                2                0                16                0                8                1 
[1] Started=Randomized
[2] Started=Randomized.
[3] Completed study



  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.
160 participants were randomized and included in analysis. Of these, 1 participant was not treated: at screening, the site felt that Mini-Mental State Examination (MMSE) score was artificially low due to language issue. Hence, study enrollment was approved. Later, participant discontinued from study, which was recorded as major protocol deviation.

Reporting Groups
  Description
ACC 3 µg+QS-21 / ACC 3 µg+QS-21 Participants received 3 μg of ACC-001 and 50 μg of QS-21 in the lead-in study and in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
QS-21 / ACC 3 µg+QS-21 Participants received 50 μg of QS-21 in the lead-in study and 3 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
ACC 10 µg+QS-21 / ACC 10 µg+QS-21 Participants received 10 μg of ACC-001 and 50 μg of QS-21 in the lead-in study and in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
ACC 10 µg / ACC 10 µg+QS-21 Participants received 10 μg of ACC-001 in the lead-in study and 10 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
QS-21 / ACC 10 µg+QS-21 Participants received 50 μg of QS-21 in the lead-in study and 10 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
PBS / ACC 10 μg+QS-21 Participants received PBS in the lead-in study and 10 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
ACC 30 µg+QS-21 / ACC 30 µg+QS-21 Participants received 30 μg of ACC-001 and 50 μg of QS-21 in the lead-in study and in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
ACC 30 µg / ACC 30 µg+QS-21 Participants received 30 μg of ACC-001 in the lead-in study and 30 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
QS-21 / ACC 30 µg+QS-21 Participants received 50 μg of QS-21 in the lead-in study and 30 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
PBS / ACC 30 μg+QS-21 Participants received PBS in the lead-in study and 30 μg of ACC-001 and 50 μg of QS-21 in the extension study. Test article was given by intramuscular injection into the deltoid muscle at 0, 6, 12, and 18 months.
Total Total of all reporting groups

Baseline Measures
   ACC 3 µg+QS-21 / ACC 3 µg+QS-21   QS-21 / ACC 3 µg+QS-21   ACC 10 µg+QS-21 / ACC 10 µg+QS-21   ACC 10 µg / ACC 10 µg+QS-21   QS-21 / ACC 10 µg+QS-21   PBS / ACC 10 μg+QS-21   ACC 30 µg+QS-21 / ACC 30 µg+QS-21   ACC 30 µg / ACC 30 µg+QS-21   QS-21 / ACC 30 µg+QS-21   PBS / ACC 30 μg+QS-21   Total 
Overall Participants Analyzed 
[Units: Participants]
 21   6   41   25   5   9   27   6   16   4   160 
Age 
[Units: Years]
Mean (Standard Deviation)
 68.7  (6.94)   67.7  (9.52)   69.7  (9.29)   72.4  (9.12)   75.2  (8.23)   69.6  (7.94)   71.3  (9.20)   66.3  (9.42)   69.5  (6.95)   75.8  (7.89)   70.4  (8.61) 
Gender 
[Units: Participants]
                     
Female   11   4   21   12   3   8   16   3   14   2   94 
Male   10   2   20   13   2   1   11   3   2   2   66 
Race/Ethnicity, Customized 
[Units: Participants]
                     
Asian   0   0   0   0   0   0   0   0   0   0   0 
Black or African American   0   0   1   0   1   0   1   0   0   0   3 
Other   1   0   0   0   0   0   0   0   0   0   1 
White   20   6   40   25   4   9   26   6   16   4   156 
MMSE Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 16.7  (4.64)   18.3  (5.61)   18.4  (5.92)   19.6  (5.45)   21.8  (4.21)   20.0  (6.14)   18.7  (4.98)   20.5  (4.76)   19.1  (4.84)   20.0  (4.69)   18.8  (5.29) 
[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.
MMSE Ranges [1] 
[Units: Participants]
                     
MMSE score >26   0   0   5   3   1   1   1   0   1   0   12 
MMSE score 21-26   5   2   9   7   2   3   8   3   6   3   48 
MMSE score 16-20   5   2   12   10   2   3   11   2   6   0   53 
MMSE score 10-15   10   2   15   5   0   2   7   1   3   1   46 
MMSE score <10   1   0   0   0   0   0   0   0   0   0   1 
[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
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Treatment-emergent AEs or Serious Adverse Events (SAEs)   [ Time Frame: 24 months ]

2.  Other Pre-specified:   GMTs of Anti-A-beta Immunoglobulin M (IgM) Using ELISA at Weeks 0, 4, 12, 24, 30, 36, 50, 56, 66, 76, 82, and 104   [ Time Frame: Weeks 0, 4, 12, 24, 30, 36, 50, 56, 66, 76, 82, and 104 ]

3.  Other Pre-specified:   Change From Baseline GMTs of Anti-A-beta IgG Subtypes Using ELISA at Visits Where an IgG Total Response is Measurable (at Weeks 0, 4, 12, 24, 30, 36, 50, 56, 66, 76, 82, and 104 if Applicable)   [ Time Frame: Weeks 0, 4, 12, 24, 30, 36, 50, 56, 66, 76, 82, and 104 ]

4.  Other Pre-specified:   Geometric Mean Titers (GMTs) of Anti-A-beta Immunoglobulin G (IgG) Total Using an Enzyme-linked Immunosorbent Assay (ELISA) at Weeks 0, 4, 12, 24, 30, 36, 50, 56, 66, 76, 82, and 104   [ Time Frame: Weeks 0, 4, 12, 24, 30, 36, 50, 56, 66, 76, 82, and 104 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
In 2013 the sponsor decided that ACC-001 would not be further developed in mild to moderate Alzheimer's disease, study drug administration was discontinued, and remaining participants were followed for safety for up to 6 months after last injection.


  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: NCT00960531     History of Changes
Other Study ID Numbers: 3134K1-2205
B2571008 ( Other Identifier: Alias Study Number )
Study First Received: August 13, 2009
Results First Received: December 18, 2014
Last Updated: March 2, 2016
Health Authority: United States: Food and Drug Administration