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Study Evaluating The Efficacy And Safety Of Bapineuzumab In Alzheimer Disease Patients

This study has been terminated.
(The study was terminated on August 6, 2012, because 2 large Phase 3 studies showed no clinical benefit. This decision was not based on any new safety concerns.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00667810
First received: April 24, 2008
Last updated: December 4, 2015
Last verified: December 2015
Results First Received: October 22, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer Disease
Interventions: Drug: bapineuzumab
Drug: placebo

  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
The study was terminated on 06 August 2012 due to lack of clinical efficacy observed in completed studies ELN115727-301 (ApoE4 non-carriers) and ELN115727-302. A total of 329 participants had completed the study up to and including Week 78 before the decision was taken to terminate the study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study originally included bapineuzumab 2.0 mg/kg dose level, which was discontinued on 02 April 2009 based on input from independent safety monitoring committee. It was estimated at the time that about 10 participants received 2.0mg/kg. These participants are not included in the efficacy analyses.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by intravenous (IV) infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 2.0 mg/kg Participants received 2.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.

Participant Flow:   Overall Study
    Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo   Bapineuzumab 2.0 mg/kg
STARTED   269   264   346   11 
Treated   267   263   344   11 
COMPLETED   102   94   124   9 
NOT COMPLETED   167   170   222   2 
Adverse Event                13                14                19                1 
Death                1                1                3                0 
Lack of Efficacy                1                0                2                0 
Lost to Follow-up                1                4                2                0 
Physician Decision                1                1                2                0 
Protocol Violation                0                2                0                0 
Withdrawal by Subject                14                20                29                1 
Discontinuation of Study by Sponsor                130                118                155                0 
Failed to Return                0                0                2                0 
Loss of Caregiver                0                1                3                0 
Vasogenic Edema Recurrence                0                3                0                0 
Not specified                6                6                5                0 



  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.
Safety population included all randomized participants who received at least one infusion or portion of an infusion of study drug.

Reporting Groups
  Description
Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Placebo Participants received placebo by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Bapineuzumab 2.0 mg/kg Participants received 2.0 mg/kg bapineuzumab by IV infusion every 13 weeks, for a total of 6 infusions over the course of the study. A final follow-up visit was performed at Week 78, 13 weeks after the last infusion.
Total Total of all reporting groups

Baseline Measures
   Bapineuzumab 0.5 mg/kg   Bapineuzumab 1.0 mg/kg   Placebo   Bapineuzumab 2.0 mg/kg   Total 
Overall Participants Analyzed 
[Units: Participants]
 267   263   344   11   885 
Age 
[Units: Years]
Mean (Standard Deviation)
 71.4  (9.38)   70.8  (9.73)   69.9  (9.76)   66.5  (7.94)   70.6  (9.63) 
Age, Customized 
[Units: Years]
         
<65 years   73   81   115   6   275 
≥65 years   194   182   229   5   610 
Gender 
[Units: Number of participants]
         
Female   151   150   199   4   504 
Male   116   113   145   7   381 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   The Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)/11 Total Score at Week 78   [ Time Frame: 78 weeks ]

2.  Primary:   The Change From Baseline in the Disability Assessment for Demential (DAD) Total Score at Week 78   [ Time Frame: 78 weeks ]

3.  Secondary:   The Change From Baseline in Brain Amyloid Burden at Week 71.   [ Time Frame: 71 Weeks ]

4.  Secondary:   The Change From Baseline in Phospho-tau Levels in the Cerebrospinal Fluid (CSF) at Week 71.   [ Time Frame: 71 Weeks ]

5.  Secondary:   The Change From Baseline in Brain Volume at Week 71   [ Time Frame: 71 Weeks ]

6.  Secondary:   Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78   [ Time Frame: 39 Weeks ]

7.  Secondary:   Divergence of Effect on the DAD Total Scores From Week 39 to Week 78   [ Time Frame: 39 weeks ]

8.  Secondary:   Time to Median Placebo Deterioration on ADAS-Cog/11 Total Score (European Union [EU] Analysis Plan)   [ Time Frame: 78 Weeks ]

9.  Secondary:   Time to First Clinically Meaningful Deterioration on ADAS-Cog/11 Total Score (United States [US] Analysis Plan)   [ Time Frame: 78 weeks ]

10.  Secondary:   Time to Median Placebo Deterioration on DAD Total Score   [ Time Frame: 78 Weeks ]

11.  Secondary:   Time to First Clinically Meaningful Deterioration on DAD Total Score (US Analysis Plan)   [ Time Frame: 78 Weeks ]

12.  Secondary:   Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (European Union Analysis Plan)   [ Time Frame: 78 Weeks ]

13.  Secondary:   Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (US Analysis Plan)   [ Time Frame: 78 Weeks ]

14.  Secondary:   Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (European Union Analysis Plan)   [ Time Frame: 78 Weeks ]

15.  Secondary:   Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (US Analysis Plan)   [ Time Frame: 78 weeks ]

16.  Secondary:   Change From Baseline in Dependence Scale Total Score at Week 78   [ Time Frame: 78 Weeks ]

17.  Secondary:   Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Total Score at Week 78   [ Time Frame: 78 Weeks ]


  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
The impact of study termination, the shorter observational periods and the resulting small sample size coupled with not having enough participants with post baseline assessments for various reasons were limiting factors for data interpretation.


  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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00667810     History of Changes
Obsolete Identifiers: NCT00909623
Other Study ID Numbers: 3133K1-3000
B2521001 ( Other Identifier: Alias Study Number )
2007-005994-79 ( EudraCT Number )
Study First Received: April 24, 2008
Results First Received: October 22, 2013
Last Updated: December 4, 2015
Health Authority: United States: Food and Drug Administration