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Study Evaluating The Safety Of AAB-003 (PF-05236812) In Subjects With Alzheimer's Disease

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01193608
First Posted: September 2, 2010
Last Update Posted: February 23, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Information provided by (Responsible Party):
Pfizer
Results First Submitted: June 15, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer's Disease
Interventions: Drug: AAB-003 (PF-05236812)
Other: 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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
AAB-003 0.5 mg/kg Participants received AAB-003 0.5 milligram/kilogram (mg/kg) 1-hour intravenous (IV) infusion (infusion of AAB-003 and 20 milliliter (mL) normal saline flush of IV line) once every 13 weeks on Day 1, Week 13 and Week 26 for a total of 3 infusions over the course of study. A final follow-up visit was performed at Week 39, 13 weeks after the last infusion.
AAB-003 1 mg/kg Participants received AAB-003 1 mg/kg 1-hour IV infusion (infusion of AAB-003 and 20 mL normal saline flush of IV line) once every 13 weeks on Day 1, Week 13 and Week 26 for a total of 3 infusions over the course of study. A final follow-up visit was performed at Week 39, 13 weeks after the last infusion.
AAB-003 2 mg/kg Participants received AAB-003 2 mg/kg 1-hour IV infusion (infusion of AAB-003 and 20 mL normal saline flush of IV line) once every 13 weeks on Day 1, Week 13 and Week 26 for a total of 3 infusions over the course of study. A final follow-up visit was performed at Week 39, 13 weeks after the last infusion.
AAB-003 4 mg/kg Participants received AAB-003 4 mg/kg 1-hour IV infusion (infusion of AAB-003 and 20 mL normal saline flush of IV line) once every 13 weeks on Day 1, Week 13 and Week 26 for a total of 3 infusions over the course of study. A final follow-up visit was performed at Week 39, 13 weeks after the last infusion.
AAB-003 8 mg/kg Participants received AAB-003 8 mg/kg 1-hour IV infusion (infusion of AAB-003 and 20 mL normal saline flush of IV line) once every 13 weeks on Day 1, Week 13 and Week 26 for a total of 3 infusions over the course of study. A final follow-up visit was performed at Week 39, 13 weeks after the last infusion.
Placebo Participants received placebo matched to AAB-003 1-hour IV infusion (infusion of placebo matched to AAB-003 and 20 mL normal saline flush of IV line) once every 13 weeks on Day 1, Week 13 and Week 26 for a total of 3 infusions over the course of study. A final follow-up visit was performed at Week 39, 13 weeks after the last infusion.

Participant Flow:   Overall Study
    AAB-003 0.5 mg/kg   AAB-003 1 mg/kg   AAB-003 2 mg/kg   AAB-003 4 mg/kg   AAB-003 8 mg/kg   Placebo
STARTED   6   6   16   17   24   19 
COMPLETED   6   4   14   14   19   17 
NOT COMPLETED   0   2   2   3   5   2 
Other                0                1                0                0                0                0 
Withdrawal by Subject                0                1                2                3                3                0 
Lost to Follow-up                0                0                0                0                1                2 
Adverse Event                0                0                0                0                1                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.
All participants who were randomized.

Reporting Groups
  Description
AAB-003 0.5 mg/kg Participants received AAB-003 0.5 mg/kg by IV infusion on Day 1, Week 13 and Week 26
AAB-003 1 mg/kg Participants received AAB-003 1 mg/kg by IV infusion on Day 1, Week 13 and Week 26
AAB-003 2 mg/kg Participants received AAB-003 2 mg/kg by IV infusion on Day 1, Week 13 and Week 26
AAB-003 4 mg/kg Participants received AAB-003 4 mg/kg by IV infusion on Day 1, Week 13 and Week 26
AAB-003 8 mg/kg Participants received AAB-003 8 mg/kg by IV infusion on Day 1, Week 13 and Week 26
Placebo Participants received placebo matched to AAB-003 by IV infusion on Day 1, Week 13 and Week 26
Total Total of all reporting groups

Baseline Measures
   AAB-003 0.5 mg/kg   AAB-003 1 mg/kg   AAB-003 2 mg/kg   AAB-003 4 mg/kg   AAB-003 8 mg/kg   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 6   6   16   17   24   19   88 
Age 
[Units: Years]
Mean (Standard Deviation)
 64.5  (6.4)   67.2  (7.4)   70.7  (10.8)   71.5  (8.8)   64.5  (7.6)   71.1  (7.6)   68.6  (8.8) 
Gender 
[Units: Participants]
Count of Participants
             
Female      4  66.7%      3  50.0%      14  87.5%      9  52.9%      14  58.3%      8  42.1%      52  59.1% 
Male      2  33.3%      3  50.0%      2  12.5%      8  47.1%      10  41.7%      11  57.9%      36  40.9% 
Race/Ethnicity, Customized 
[Units: Participants]
             
White   4   3   5   6   12   11   41 
Black   2   2   1   0   1   3   9 
Asian   0   1   10   11   11   5   38 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Treatment-Emergent Adverse Events (TEAEs)   [ Time Frame: Baseline up to 39 Weeks and at Early Withdrawal ]

2.  Primary:   Number of Participants With Laboratory Abnormalities   [ Time Frame: Baseline up to 39 Weeks and at Early Withdrawal ]

3.  Primary:   Number of Participants With Vital Signs of Potential Clinical Concern   [ Time Frame: Baseline up to 39 Weeks and at Early Withdrawal ]

4.  Primary:   Number of Participants With Abnormal Physical Examination Findings   [ Time Frame: Baseline up to 39 Weeks and at Early Withdrawal ]

5.  Primary:   Number of Participants With Abnormal Neurological Examination Findings   [ Time Frame: Screening, Day 1 (Baseline) and Weeks 1,6,13,19,26,32, and 39, and at Early Withdrawal ]

6.  Primary:   Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]

7.  Primary:   Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]

8.  Primary:   Average Concentration (Cavg) for AAB-003 in Serum at Day 1   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]

9.  Primary:   Average Concentration (Cavg) for AAB-003 in Serum at Week 26   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]

10.  Primary:   Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]

11.  Primary:   Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]

12.  Primary:   Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]

13.  Primary:   Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]

14.  Primary:   Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]

15.  Primary:   Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]

16.  Primary:   Systemic Clearance (CL) for AAB-003 in Serum at Day 1   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]

17.  Primary:   Systemic Clearance (CL) for AAB-003 in Serum at Week 26   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]

18.  Primary:   Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]

19.  Primary:   Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]

20.  Primary:   Serum Decay Half-Life (t1/2) for AAB-003 at Day 1   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]

21.  Primary:   Serum Decay Half-Life (t1/2) for AAB-003 at Week 26   [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]

22.  Primary:   Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)   [ Time Frame: Baseline up to Week 39 or Early Withdrawal ]

23.  Primary:   Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding   [ Time Frame: Baseline up to Week 32. ]

24.  Primary:   Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit   [ Time Frame: Day 1, Week 13, and Week 26 ]

25.  Primary:   Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria   [ Time Frame: Baseline, Weeks 1,13,16,26,39 or Early Withdrawal ]

26.  Other Pre-specified:   Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum   [ Time Frame: Day 1 (predose), Week 13 (predose), Week 26 (predose) and Week 39 or Early Withdrawal ]

27.  Other Pre-specified:   Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39   [ Time Frame: Baseline, Weeks 13, 26 and 39 ]

28.  Other Pre-specified:   Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39   [ Time Frame: Baseline, Weeks 13, 26 and 39 ]

29.  Other Pre-specified:   Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39   [ Time Frame: Baseline, Weeks 13, 26 and 39 ]

30.  Other Pre-specified:   Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39   [ Time Frame: Baseline, Weeks 26 and 39 ]

31.  Other Pre-specified:   Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39   [ Time Frame: Baseline, Weeks 13, 26 and 39 ]

32.  Other Pre-specified:   Cerebrospinal Fluid (CSF) Concentration of AAB-003 at Week 32   [ Time Frame: Week 32 or Early Withdrawal ]

33.  Other Pre-specified:   Change From Baseline in CSF Amyloid-beta x-40 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups   [ Time Frame: Baseline and Week 32 ]

34.  Other Pre-specified:   CSF Amyloid-beta x-40 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups   [ Time Frame: Baseline and Week 32 ]

35.  Other Pre-specified:   Change From Baseline in CSF Amyloid-beta x-42 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups   [ Time Frame: Baseline and Week 32 ]

36.  Other Pre-specified:   CSF Amyloid-beta x-42 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups   [ Time Frame: Baseline and Week 32 ]

37.  Other Pre-specified:   Change From Baseline in CSF Tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups   [ Time Frame: Baseline and Week 32 ]

38.  Other Pre-specified:   CSF Tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups   [ Time Frame: Baseline and Week 32 ]

39.  Other Pre-specified:   Change From Baseline in CSF P-tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups   [ Time Frame: Baseline and Week 32 ]

40.  Other Pre-specified:   CSF P-tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups   [ Time Frame: Baseline and Week 32 ]

41.  Other Pre-specified:   Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40   [ Time Frame: Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]

42.  Other Pre-specified:   Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40   [ Time Frame: Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]

43.  Other Pre-specified:   Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Amyloid-Beta x-40   [ Time Frame: Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]

44.  Other Pre-specified:   Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Amyloid-Beta x-40   [ Time Frame: Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]

45.  Other Pre-specified:   Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40   [ Time Frame: Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]

46.  Other Pre-specified:   Plasma Decay Half-Life (t1/2) for Amyloid-Beta x-40   [ Time Frame: Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]


  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


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

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01193608     History of Changes
Other Study ID Numbers: B2601001
3245K1-1000 ( Other Identifier: Alias Study Number )
First Submitted: August 19, 2010
First Posted: September 2, 2010
Results First Submitted: June 15, 2016
Results First Posted: February 23, 2017
Last Update Posted: February 23, 2017