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Study Evaluating Single Ascending Doses of AAB-001 Vaccine SAD Japanese Patients With Alzheimers Disease

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.
 
ClinicalTrials.gov Identifier: NCT00397891
Recruitment Status : Completed
First Posted : November 10, 2006
Results First Posted : September 4, 2014
Last Update Posted : September 4, 2014
Sponsor:
Information provided by (Responsible Party):
Wyeth is now a wholly owned subsidiary of Pfizer

Tracking Information
First Submitted Date  ICMJE November 8, 2006
First Posted Date  ICMJE November 10, 2006
Results First Submitted Date  ICMJE August 20, 2014
Results First Posted Date  ICMJE September 4, 2014
Last Update Posted Date September 4, 2014
Study Start Date  ICMJE October 2006
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2014)
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 52 ]
    An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between dose of study medication and up to 52 weeks after the dose that were absent before treatment or that worsened relative to pre-treatment state.
  • Number of Participants With Clinically Significant Changes in Physical Examinations [ Time Frame: Screening up to Week 52 ]
    Physical examination included the assessment of abdomen, back/spinal, breasts, external genitalia, extremities, general appearance, head, eyes, ears, nose, throat (HEENT), heart, lungs, lymph nodes and skin.
  • Number of Participants With Vital Signs of Potential Clinical Importance [ Time Frame: Baseline up to Week 52 ]
    Criteria for determining potentially clinically important (PCI) vital signs was described as: supine blood pressure (BP)- systolic (greater than or equal to [>=]160 millimeter mercury [mm Hg] or less than or equal to [<=]90 mm Hg and increase or decrease of >=20 mm Hg compared to baseline value), supine diastolic BP (>=100 mm Hg or <= 50 mm Hg and increase or decrease of >=15 mm Hg compared to baseline value), supine pulse rate (>=120 beats per minute (bpm) or <=45 bpm and increase or decrease of >15 bpm compared to baseline value), body temperature (>38.3 degree Celsius and <35 degree Celsius).
  • Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance [ Time Frame: Screening up to Week 16 ]
    Criteria for determining PCI ECG result was described as: heart rate (>=120 bpm or <=45 bpm and increase or decrease of >15 bpm compared to baseline value), PR interval (>=220 millisecond (msec) and change of >=20 msec compared to baseline value), QRS interval (>=120 msec), corrected QT (QTc) interval for men (>450 msec), QTc interval for women (>470 msec).
  • Number of Participants With Laboratory Test Results of Potential Clinical Importance [ Time Frame: Week 1 up to Week 52 ]
    Criteria for PCI laboratory results: hematology (hematocrit [decrease >=5%], hemoglobin [decrease >=20gram/liter {g/L}] from baseline, white blood cells [<3], neutrophils [<1.5], platelet [<100], eosinophils [>0.5] *10^9/L); blood chemistry (sodium [>5], potassium [>0.5], fasting glucose [>0.83], phosphorous [>0.162] millimole/L [mmol/L] above upper limit of normal [ULN] and below lower limit of normal [LLN], non-fasting glucose >5 mmol/L above ULN, >0.56 mmol/L below LLN, creatinine >1.36*ULN, blood urea nitrogen >1.5*ULN, calcium [change of >=0.25 mmol/L], total protein [change of >=20g/L], albumin [change of >=10g/L], uric acid [change of >0.119mmol/L] from baseline and outside normal limits); Liver function tests (alanine aminotransferase/serum glutamic pyruvic transaminase [ALT/SGPT] and aspartate aminotransferase/serum glutamic oxaloacetic transaminase [AST/SGOT] >2*ULN, total bilirubin >2*ULN, alkaline phosphatase >1.5*ULN, gamma-glutamyl-transpeptidase [GGT] >3*ULN).
  • Number of Participants With Clinically Significant Changes in Neurological Examinations [ Time Frame: Screening up to Week 52 ]
    Neurological examination included the assessment of mental status, cranial nerves, visual fields, sensory, motor, gait, primitive reflexes and tendon reflexes.
  • Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 [ Time Frame: Baseline, Week 6 ]
    MMSE measures general cognitive functioning: orientation to time (range: 0 to 5) and orientation to place (range: 0 to 5), registration of 3 words (range: 0 to 3), attention and calculation (range: 0 to 5), recall of 3 words (range: 0 to 3), naming (range: 0 to 2), repetition (range: 0 to 1), comprehension (range: 0 to 3), reading (range: 0 to 1), writing (range: 0 to 1) and drawing (range: 0 to 1). Total score is the sum of sub-scores; total score ranges from 0 to 30, higher score indicates better cognitive state.
  • Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 16 [ Time Frame: Baseline, Week 16 ]
    MMSE measures general cognitive functioning: orientation to time (range: 0 to 5) and orientation to place (range: 0 to 5), registration of 3 words (range: 0 to 3), attention and calculation (range: 0 to 5), recall of 3 words (range: 0 to 3), naming (range: 0 to 2), repetition (range: 0 to 1), comprehension (range: 0 to 3), reading (range: 0 to 1), writing (range: 0 to 1) and drawing (range: 0 to 1). Total score is the sum of sub-scores; total score ranges from 0 to 30, higher score indicates better cognitive state.
  • Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 52 [ Time Frame: Baseline, Week 52 ]
    MMSE measures general cognitive functioning: orientation to time (range: 0 to 5) and orientation to place (range: 0 to 5), registration of 3 words (range: 0 to 3), attention and calculation (range: 0 to 5), recall of 3 words (range: 0 to 3), naming (range: 0 to 2), repetition (range: 0 to 1), comprehension (range: 0 to 3), reading (range: 0 to 1), writing (range: 0 to 1) and drawing (range: 0 to 1). Total score is the sum of sub-scores; total score ranges from 0 to 30, higher score indicates better cognitive state.
Original Primary Outcome Measures  ICMJE
 (submitted: November 9, 2006)
Safety, tolerability, Pharmacokinetics
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2014)
  • Maximum Observed Serum Concentration (Cmax) of Bapineuzumab [ Time Frame: 0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52 ]
    Participants who received bapineuzumab were reported.
  • Time to Reach Maximum Observed Serum Concentration (Tmax) of Bapineuzumab [ Time Frame: 0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52 ]
    Participants who received bapineuzumab were reported.
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Bapineuzumab [ Time Frame: 0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52 ]
    AUC is a measure of the serum concentration of the drug over time. AUC (0-t) is area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). Participants who received bapineuzumab were reported.
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Bapineuzumab [ Time Frame: 0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52 ]
    AUC is a measure of the serum concentration of the drug over time. AUC (0 - ∞) is area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). Participants who received bapineuzumab were reported.
  • Systemic Clearance (CL) of Bapineuzumab [ Time Frame: 0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52 ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body. Participants who received bapineuzumab were reported.
  • Volume of Distribution at Steady State (Vss) of Bapineuzumab [ Time Frame: 0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52 ]
    Volume of distribution is defined as the theoretical blood volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Participants who received bapineuzumab were reported.
  • Mean Residence Time of Bapineuzumab [ Time Frame: 0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52 ]
    MRT is average time for which the drug molecules resides in the body, after administration. It is calculated as area under the serum concentration versus time first moment curve from time zero (pre-dose) to extrapolated infinite time (AUMC [0 - ∞]) divided by area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (AUC[0 - ∞]). AUMC (0-∞) is calculated as AUMC(0-inf)= AUMCt + [(t x Ct) / kel] + (Ct / kel^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method, Ct is the concentration at time t and kel is the terminal phase rate constant. Participants who received bapineuzumab were reported.
  • Serum Decay Half-Life (t1/2) of Bapineuzumab [ Time Frame: 0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52 ]
    Serum decay half-life is the time measured for the serum concentration to decrease by one half. Participants who received bapineuzumab were reported.
  • Serum Bapineuzumab Concentrations [ Time Frame: 0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6, 24, 48, 168, 336, 672, 1008, 1344, 1848, 2184, 2688, 4368, 8736 hours post start of infusion ]
    Serum bapineuzumab concentration was determined by using a validated enzyme-linked immunosorbent assay (ELISA) method. Participants who received bapineuzumab were reported.
  • Number of Participants With Positive Serum Anti-Bapineuzumab Antibody [ Time Frame: Baseline (Day 1) up to Week 52 ]
    Serum anti-bapineuzumab antibody concentration was determined by using a validated ELISA method.
  • Plasma Amyloid-beta (x-40) Concentrations [ Time Frame: 0 (pre-infusion), 1, 6, 24, 336, 1008, 2184, 2688, 4368, 8736 hours post start of infusion ]
    Amyloid-beta (A-beta) is a peptide fragment of the amyloid precursor protein which is one of the characteristic hallmarks of Alzheimer's disease (AD). Total plasma amyloid-beta (x-40) was determined using a validated ELISA method.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating Single Ascending Doses of AAB-001 Vaccine SAD Japanese Patients With Alzheimers Disease
Official Title  ICMJE A Multicenter, Randomized, Double-blind, Placebo-controlled, Safety, Tolerability, and Pharmakokinetic Study of Single Ascending Doses of AAB-001 in Japanese Patients With Mild to Moderate Alzheimer's Disease
Brief Summary Evaluate safety, tolerability, and pharmacokinetics of single doses of the investigational AAB-001 Vaccine in Japanese patients with Alzheimer's disease.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE Drug: bapineuzumab
The dose cohorts are as follows: 0.15 mg/kg AAB-001; 0.5 mg/kg AAB-001; 1.0 mg/kg AAB-001. Placebo is vehicle (all ingredients except active). In each dose cohort, designated as groups 1 to 3, study drug (AAB-001 or placebo) will be administered as an intravenous infusion over 1 hour.
Study Arms  ICMJE
  • Experimental: 1
    bapineuzumab 0.15 mg/kg or placebo
    Intervention: Drug: bapineuzumab
  • Experimental: 2
    bapineuzumab 0.5 mg/kg or placebo
    Intervention: Drug: bapineuzumab
  • Experimental: 3
    bapineuzumab 1.0 mg/kg or placebo
    Intervention: Drug: bapineuzumab
Publications * Arai H, Umemura K, Ichimiya Y, Iseki E, Eto K, Miyakawa K, Kirino E, Shibata N, Baba H, Tsuchiwata S. Safety and pharmacokinetics of bapineuzumab in a single ascending-dose study in Japanese patients with mild to moderate Alzheimer's disease. Geriatr Gerontol Int. 2016 May;16(5):644-50. doi: 10.1111/ggi.12516. Epub 2015 Jun 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 28, 2012)
80
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE February 2010
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of AD
  • Age 50-85
  • MMSE 14-26
  • Other Inclusion Criteria Apply

Exclusion Criteria:

  • Significant Neurological Disease
  • Major Psychiatric Disorder
  • Clinically Significant Systemic Illness
  • Other Exclusion Criteria Apply
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00397891
Other Study ID Numbers  ICMJE 3133K1-102
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Wyeth is now a wholly owned subsidiary of Pfizer
Study Sponsor  ICMJE Wyeth is now a wholly owned subsidiary of Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Wyeth is now a wholly owned subsidiary of Pfizer
Verification Date August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP