Alzheimer Disease
Conditions
Keywords
open-label, safety, antibody
Brief summary
This study will evaluate the safety and tolerability of bapineuzumab when administered by subcutaneous injection. The study is open only to subjects who participated in the preceding double-blind study (3133L1-2203 US). Subjects will receive weekly injections of bapineuzumab for 3 years (156 doses). One dosage level will be included: 5 mg/week. All subjects will receive active treatment (bapineuzumab) and no subjects will receive placebo.
Interventions
DRUGbapineuzumab
5 mg/week subcutaneous bapineuzumab
Sponsors
JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of probable Alzheimer disease * Completed preceding double-blind study (3133L1-2203 US) * MMSE score \> 9.
Exclusion criteria
* Significant brain MRI abnormalities * Clinically important psychiatric symptoms * History of stroke
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 13, 26, 39, 52, 65, 78, 91, 104, 117, 130, 143, 156, Any visit | A brain Magnetic Resonance Imaging (MRI) was obtained from all participants at Week 13 and quarterly thereafter. Participants were to meet the following criteria: screening brain MRI scan is consistent with the diagnosis of Alzheimer's Disease. Screening diagnosis of probable Alzheimer's disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria. Clinically significant MRIs were identified by the investigator. The number of participants with clinically significant MRIs are tabulated by visit and treatment group. |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic Parameters Including Maximal Serum Drug Concentration, Time to Maximal Serum Drug Concentration, and Terminal Half-life of Elimination | 36 months |
Countries
United States
Participant flow
Recruitment details
Participants who completed the parent Study NCT00663026 and met the study criteria were enrolled and randomized into each of 3 dose cohorts to receive bapineuzumab or placebo. The study was terminated early on 06 August 2012 because 2 Phase 3 studies showed no clinical benefit. The decision was not based on any new safety concerns.
Participants by arm
| Arm | Count |
|---|---|
| Bapineuzumab (5 mg + 5 mg) Participants who received 5 milligram (mg) in the parent study, in Study NCT00663026, continued to receive 5 mg bapineuzumab in the current study. | 23 |
| Bapineuzumab (10 mg + 10 mg) Participants who received 10 mg in the parent study, Study NCT00663026, received 10 mg bapineuzumab in the current study. | 21 |
| Placebo + Bapineuzumab 5mg Participants who received placebo in the parent study, Study NCT00663026, received 5 mg bapineuzumab in the current study. | 10 |
| Placebo + Bapineuzumab 10 mg Participants who received placebo in the parent study, Study NCT00663026, received 10 mg bapineuzumab in the current study. | 7 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 6 | 3 |
| Overall Study | Caregiver Request | 3 | 2 | 1 | 0 |
| Overall Study | Discontinuation of Study by Sponsor | 8 | 13 | 3 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 | 0 | 0 |
| Overall Study | Other | 2 | 0 | 0 | 2 |
| Overall Study | Physician Decision | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Bapineuzumab (5 mg + 5 mg) | Bapineuzumab (10 mg + 10 mg) | Placebo + Bapineuzumab 5mg | Placebo + Bapineuzumab 10 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 72.2 Years STANDARD_DEVIATION 8.92 | 74.0 Years STANDARD_DEVIATION 9.34 | 80.4 Years STANDARD_DEVIATION 5.54 | 70.3 Years STANDARD_DEVIATION 10.13 | 73.9 Years STANDARD_DEVIATION 9.1 |
| Age, Customized Greater than or equal to (>=) 65 years | 19 Participants | 18 Participants | 10 Participants | 5 Participants | 52 Participants |
| Age, Customized Less than (<) 65 years | 4 Participants | 3 Participants | 0 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Female | 14 Participants | 8 Participants | 6 Participants | 2 Participants | 30 Participants |
| Sex: Female, Male Male | 9 Participants | 13 Participants | 4 Participants | 5 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 23 | 16 / 21 | 10 / 10 | 6 / 7 |
| serious Total, serious adverse events | 4 / 23 | 5 / 21 | 7 / 10 | 2 / 7 |
Outcome results
Primary
Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings
A brain Magnetic Resonance Imaging (MRI) was obtained from all participants at Week 13 and quarterly thereafter. Participants were to meet the following criteria: screening brain MRI scan is consistent with the diagnosis of Alzheimer's Disease. Screening diagnosis of probable Alzheimer's disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria. Clinically significant MRIs were identified by the investigator. The number of participants with clinically significant MRIs are tabulated by visit and treatment group.
Time frame: Week 13, 26, 39, 52, 65, 78, 91, 104, 117, 130, 143, 156, Any visit
Population: The safety population included all participants who received at least 1 dose of study medication in Study NCT00916617.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 78 | 0 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 39 | 0 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 143 | 0 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 65 | 0 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 130 | 0 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 117 | 0 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Any visit | 1 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 156 | 0 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 52 | 0 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 104 | 0 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 91 | 0 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 26 | 1 Participants |
| Bapineuzumab (5 mg + 5 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 13 | 0 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 26 | 0 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Any visit | 3 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 13 | 2 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 39 | 0 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 52 | 0 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 65 | 0 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 78 | 1 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 91 | 0 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 104 | 0 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 117 | 0 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 130 | 0 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 143 | 0 Participants |
| Bapineuzumab (10 mg + 10 mg) | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 156 | 0 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 104 | 0 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 91 | 0 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 130 | 0 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 52 | 0 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 13 | 1 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Any visit | 1 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 156 | 0 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 39 | 0 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 143 | 0 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 65 | 0 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 117 | 0 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 26 | 1 Participants |
| Placebo + Bapineuzumab 5mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 78 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 143 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 78 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 13 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Any visit | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 91 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 104 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 130 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 156 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 117 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 26 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 39 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 52 | 0 Participants |
| Placebo + Bapineuzumab 10 mg | Number of Participants Reporting Clinically Significant Magnetic Resonance Imaging (MRI) Findings | Week 65 | 0 Participants |
Secondary
Pharmacokinetic Parameters Including Maximal Serum Drug Concentration, Time to Maximal Serum Drug Concentration, and Terminal Half-life of Elimination
Time frame: 36 months
Population: Because this study was terminated early, the planned pharmacokinetic analyses were not performed.