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

Alzheimer Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00397891
• Other study ID #: 3133K1-102
• Status: Completed
• Phase: Phase 1
• First received: November 8, 2006
• Last updated: August 20, 2014
• Start date: October 2006
• Est. completion date: February 2010

Study information

• Verified date: August 2014
• Source: Wyeth is now a wholly owned subsidiary of Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

Evaluate safety, tolerability, and pharmacokinetics of single doses of the investigational AAB-001 Vaccine in Japanese patients with Alzheimer's disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Japan	Pfizer Investigational Site	Chiba
Japan	Pfizer Investigational Site	Saitama
Japan	Pfizer Investigational Site	Shizuoka
Japan	Pfizer Investigational Site	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	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.	Baseline up to Week 52	Yes
Primary	Number of Participants With Clinically Significant Changes in Physical Examinations	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.	Screening up to Week 52	Yes
Primary	Number of Participants With Vital Signs of Potential Clinical Importance	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).	Baseline up to Week 52	Yes
Primary	Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance	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).	Screening up to Week 16	Yes
Primary	Number of Participants With Laboratory Test Results of Potential Clinical Importance	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).	Week 1 up to Week 52	Yes
Primary	Number of Participants With Clinically Significant Changes in Neurological Examinations	Neurological examination included the assessment of mental status, cranial nerves, visual fields, sensory, motor, gait, primitive reflexes and tendon reflexes.	Screening up to Week 52	Yes
Primary	Change From Baseline in Mini-Mental State Examination (MMSE) Score at 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.	Baseline, Week 6	Yes
Primary	Change From Baseline in Mini-Mental State Examination (MMSE) Score at 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.	Baseline, Week 16	Yes
Primary	Change From Baseline in Mini-Mental State Examination (MMSE) Score at 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.	Baseline, Week 52	Yes
Secondary	Maximum Observed Serum Concentration (Cmax) of Bapineuzumab	Participants who received bapineuzumab were reported.	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	No
Secondary	Time to Reach Maximum Observed Serum Concentration (Tmax) of Bapineuzumab	Participants who received bapineuzumab were reported.	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	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Bapineuzumab	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.	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	No
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of Bapineuzumab	AUC is a measure of the serum concentration of the drug over time. AUC (0 - 8) is area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). Participants who received bapineuzumab were reported.	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	No
Secondary	Systemic Clearance (CL) of Bapineuzumab	CL is a quantitative measure of the rate at which a drug substance is removed from the body. Participants who received bapineuzumab were reported.	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	No
Secondary	Volume of Distribution at Steady State (Vss) of Bapineuzumab	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.	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	No
Secondary	Mean Residence Time of Bapineuzumab	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 - 8]) divided by area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (AUC[0 - 8]). AUMC (0-8) 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.	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	No
Secondary	Serum Decay Half-Life (t1/2) of Bapineuzumab	Serum decay half-life is the time measured for the serum concentration to decrease by one half. Participants who received bapineuzumab were reported.	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	No
Secondary	Serum Bapineuzumab Concentrations	Serum bapineuzumab concentration was determined by using a validated enzyme-linked immunosorbent assay (ELISA) method. Participants who received bapineuzumab were reported.	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	No
Secondary	Number of Participants With Positive Serum Anti-Bapineuzumab Antibody	Serum anti-bapineuzumab antibody concentration was determined by using a validated ELISA method.	Baseline (Day 1) up to Week 52	No
Secondary	Plasma Amyloid-beta (x-40) Concentrations	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.	0 (pre-infusion), 1, 6, 24, 336, 1008, 2184, 2688, 4368, 8736 hours post start of infusion	No

External Links

•   To obtain contact information for a study center near you, click here.