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

NCT00397891 | Completed Phase 1 Results DMC

• 1 other identifier: 3133K1-102
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (9)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (11)

• 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

• 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

• 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

• 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

• 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

Study Arms (3)

1

EXPERIMENTAL

bapineuzumab 0.15 mg/kg or placebo

Drug: bapineuzumab

2

EXPERIMENTAL

bapineuzumab 0.5 mg/kg or placebo

Drug: bapineuzumab

3

EXPERIMENTAL

bapineuzumab 1.0 mg/kg or placebo

Drug: bapineuzumab

Interventions

bapineuzumab DRUG

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.

1

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AD
• Age 50-85
• MMSE 14-26

You may not qualify if:

• Significant Neurological Disease
• Major Psychiatric Disorder
• Clinically Significant Systemic Illness

Sponsors & Collaborators

• Wyeth is now a wholly owned subsidiary of Pfizer: lead

Study Sites (4)

Pfizer Investigational Site

Chiba, Japan

Location

Pfizer Investigational Site

Saitama, Japan

Location

Pfizer Investigational Site

Shizuoka, Japan

Location

Pfizer Investigational Site

Tokyo, Japan

Location

Related Publications (1)

• 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.

  PMID: 26044070 DERIVED

Related Links

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

MeSH Terms

Conditions

Alzheimer Disease

Interventions

bapineuzumab

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Wyeth

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2006
• First Posted: November 10, 2006
• Study Start: October 1, 2006
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: September 4, 2014
• Results First Posted: September 4, 2014

Record last verified: 2014-08

Locations

JP (4)