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Alzheimer DiseasePhase 1NCT00397891

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

A Phase 1 study testing bapineuzumab in people with Alzheimer Disease, run by Wyeth is now a wholly owned subsidiary of Pfizer at 4 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 50 to 85 years
Conditions the study is for
Alzheimer Disease
What is being tested?
bapineuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
4 sitesJapan
Study dates
Oct 2006to Feb 2010
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • Significant Neurological Disease
  • Major Psychiatric Disorder
  • Clinically Significant Systemic Illness
  • Other Exclusion Criteria Apply

Trial locations and contacts

4 sites in 1 country.

Japan4 sites

  • Pfizer Investigational Site

    Chiba

  • Pfizer Investigational Site

    Saitama

  • Pfizer Investigational Site

    Shizuoka

  • Pfizer Investigational Site

    Tokyo

Other trials in Japan

About this study

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

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

Being tested
bapineuzumab
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bapineuzumabDrug

    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.

  • bapineuzumabDrug

    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.

  • bapineuzumabDrug

    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 groups in NCT00397891
Study groupRoleWhat they receive
1Experimentalbapineuzumab 0.15 mg/kg or placebo
Receives: Drug: bapineuzumab
2Experimentalbapineuzumab 0.5 mg/kg or placebo
Receives: Drug: bapineuzumab
3Experimentalbapineuzumab 1.0 mg/kg or placebo
Receives: Drug: bapineuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline up to Week 52

  2. 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.

    Measured: Screening up to Week 52

  3. 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).

    Measured: Baseline up to Week 52

  4. 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).

    Measured: Screening up to Week 16

  5. 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).

    Measured: Week 1 up to Week 52

  6. 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.

    Measured: Screening up to Week 52

  7. 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.

    Measured: Baseline, Week 6

  8. 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.

    Measured: Baseline, Week 16

  9. 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.

    Measured: Baseline, Week 52

Secondary outcomes (11)

  1. Maximum Observed Serum Concentration (Cmax) of Bapineuzumab

    Participants who received bapineuzumab were reported.

    Measured: 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

  2. Time to Reach Maximum Observed Serum Concentration (Tmax) of Bapineuzumab

    Participants who received bapineuzumab were reported.

    Measured: 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

  3. 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.

    Measured: 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

  4. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Bapineuzumab

    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.

    Measured: 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

  5. 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.

    Measured: 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

  6. 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.

    Measured: 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

  7. 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 - ∞]) 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.

    Measured: 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

  8. 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.

    Measured: 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

  9. Serum Bapineuzumab Concentrations

    Serum bapineuzumab concentration was determined by using a validated enzyme-linked immunosorbent assay (ELISA) method. Participants who received bapineuzumab were reported.

    Measured: 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

  10. Number of Participants With Positive Serum Anti-Bapineuzumab Antibody

    Serum anti-bapineuzumab antibody concentration was determined by using a validated ELISA method.

    Measured: Baseline (Day 1) up to Week 52

  11. 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.

    Measured: 0 (pre-infusion), 1, 6, 24, 336, 1008, 2184, 2688, 4368, 8736 hours post start of infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Nov 2006 (estimated)
  2. Study startOct 2006
  3. Primary completionFeb 2010
  4. Study completionFeb 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00397891
Sponsor's protocol ID
3133K1-102
Status last verified
Aug 2014
First submitted
8 Nov 2006
Last updated
4 Sep 2014
Data monitoring committee
Yes

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.

    PubMed 26044070

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bapineuzumab in people with Alzheimer Disease, run by Wyeth is now a wholly owned subsidiary of Pfizer at 4 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) (time frame: Baseline up to Week 52). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00397891, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2014.

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