Study Evaluating Single Ascending Doses of AAB-001 Vaccine SAD Japanese Patients With Alzheimers Disease
- Registration Number
- NCT00397891
- Lead Sponsor
- Wyeth is now a wholly owned subsidiary of Pfizer
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
- Diagnosis of AD
- Age 50-85
- MMSE 14-26
- Other Inclusion Criteria Apply
- Significant Neurological Disease
- Major Psychiatric Disorder
- Clinically Significant Systemic Illness
- Other Exclusion Criteria Apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 bapineuzumab bapineuzumab 0.5 mg/kg or placebo 1 bapineuzumab bapineuzumab 0.15 mg/kg or placebo 3 bapineuzumab bapineuzumab 1.0 mg/kg or placebo
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) 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 Laboratory Test Results of Potential Clinical Importance 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).
Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 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.
Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance 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 Clinically Significant Changes in Physical Examinations 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 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 Clinically Significant Changes in Neurological Examinations 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 16 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 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.
- Secondary Outcome Measures
Name Time Method Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Bapineuzumab 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.
Volume of Distribution at Steady State (Vss) of Bapineuzumab 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 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.
Maximum Observed Serum Concentration (Cmax) of Bapineuzumab 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.
Number of Participants With Positive Serum Anti-Bapineuzumab Antibody Baseline (Day 1) up to Week 52 Serum anti-bapineuzumab antibody concentration was determined by using a validated ELISA method.
Systemic Clearance (CL) of Bapineuzumab 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.
Time to Reach Maximum Observed Serum Concentration (Tmax) of Bapineuzumab 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 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.
Serum Bapineuzumab Concentrations 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.
Serum Decay Half-Life (t1/2) of Bapineuzumab 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.
Plasma Amyloid-beta (x-40) Concentrations 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.
Trial Locations
- Locations (1)
Pfizer Investigational Site
🇯🇵Tokyo, Japan