Alzheimer Disease
Conditions
Keywords
antibody, immunotherapy
Brief summary
The study will evaluate the safety and effectiveness of bapineuzumab for the treatment of mild to moderate Alzheimer disease. Subjects will be in the study for six months and will receive subcutaneous injections once per week.
Interventions
DRUGbapineuzumab
5 mg bapineuzumab subcutaneous injection once per week for 6 months
DRUGplacebo
Placebo subcutaneous injection once per week for 6 months
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of probable Alzheimer Disease according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria * Mini-Mental State Examination (MMSE) score 16-26
Exclusion criteria
* Magnetic Resonance Imaging (MRI) showing other brain abnormalities * Other diagnosed neurological or psychiatric disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 30 days after Week 25 dose | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was 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 first dose of study drug and up to 30 days after Week 25 dose that were absent before treatment or that worsened relative to pretreatment state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Serum Concentration at Steady State (Cavg,ss) | Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | Average plasma concentration at steady state (Cavg,ss) = AUCtau divided by dosing interval (1 week). AUCtau is the area under the plasma concentration time curve (AUC) at steady state from time zero (pre-dose) to end of dosing interval (tau), here dosing interval is 1 week. |
| Serum Decay Half-Life (t1/2) | Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | Serum decay half-life is the time measured for the serum concentration to decrease by one half. |
| Maximum Observed Serum Concentration (Cmax) | Predose, 4 hours [hrs] postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | — |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | AUCtau is the area under the serum concentration time curve (AUC) at steady state from time zero (pre-dose) to end of dosing interval (tau), here dosing interval is 1 week. |
| Apparent Systemic Clearance (CL/F) | Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after subcutaneous dose (apparent systemic clearance) is influenced by the fraction (F) of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Steady-state apparent systemic clearance (CL/F) was calculated as dose/AUC tau. |
| Time to Reach Maximum Observed Serum Concentration (Tmax) | Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matched to bapineuzumab subcutaneous injection once weekly for 6 months. | 19 |
| Bapineuzumab 5 mg Bapineuzumab 5 milligram (mg) subcutaneous injection once weekly for 6 months. | 29 |
| Bapineuzumab 10 mg Bapineuzumab 10 mg subcutaneous injection once weekly for 6 months. | 31 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 3 |
| Overall Study | Caregiver Request | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Other | 1 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Bapineuzumab 5 mg | Bapineuzumab 10 mg | Total |
|---|---|---|---|---|
| Age Continuous | 76.16 years STANDARD_DEVIATION 8.63 | 71.28 years STANDARD_DEVIATION 8.73 | 72.42 years STANDARD_DEVIATION 8.83 | 72.90 years STANDARD_DEVIATION 8.85 |
| Sex: Female, Male Female | 8 Participants | 18 Participants | 12 Participants | 38 Participants |
| Sex: Female, Male Male | 11 Participants | 11 Participants | 19 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 19 | 22 / 29 | 27 / 31 |
| serious Total, serious adverse events | 1 / 19 | 2 / 29 | 3 / 31 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was 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 first dose of study drug and up to 30 days after Week 25 dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline up to 30 days after Week 25 dose
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 16 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 participants |
| Bapineuzumab 5 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 22 participants |
| Bapineuzumab 5 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 participants |
| Bapineuzumab 10 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 3 participants |
| Bapineuzumab 10 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 28 participants |
Secondary
Apparent Systemic Clearance (CL/F)
Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after subcutaneous dose (apparent systemic clearance) is influenced by the fraction (F) of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Steady-state apparent systemic clearance (CL/F) was calculated as dose/AUC tau.
Time frame: Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12
Population: PK analysis set included all participants who provided data for the estimation of at least 1 of the relevant PK parameters (Cmax, tmax, AUC, t1/2, CL/F and Vz/F). Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Systemic Clearance (CL/F) | 0.16 milliliter/hour/kilogram (mL/hr/kg) | Standard Deviation 0.05 |
| Bapineuzumab 5 mg | Apparent Systemic Clearance (CL/F) | 0.132 milliliter/hour/kilogram (mL/hr/kg) | Standard Deviation 0.069 |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
AUCtau is the area under the serum concentration time curve (AUC) at steady state from time zero (pre-dose) to end of dosing interval (tau), here dosing interval is 1 week.
Time frame: Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12
Population: PK analysis set included all participants who provided data for the estimation of at least 1 of the relevant PK parameters (Cmax, tmax, AUC, t1/2, CL/F and Vz/F). Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 524675.88 ng*hr/mL | Standard Deviation 180451.56 |
| Bapineuzumab 5 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 1161266.63 ng*hr/mL | Standard Deviation 361056.04 |
Secondary
Average Serum Concentration at Steady State (Cavg,ss)
Average plasma concentration at steady state (Cavg,ss) = AUCtau divided by dosing interval (1 week). AUCtau is the area under the plasma concentration time curve (AUC) at steady state from time zero (pre-dose) to end of dosing interval (tau), here dosing interval is 1 week.
Time frame: Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12
Population: PK analysis set included all participants who provided data for the estimation of at least 1 of the relevant PK parameters (Cmax, tmax, AUC, t1/2, CL/F and Vz/F). Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Serum Concentration at Steady State (Cavg,ss) | 3123.071 ng/mL | Standard Deviation 1074.116 |
| Bapineuzumab 5 mg | Average Serum Concentration at Steady State (Cavg,ss) | 6912.301 ng/mL | Standard Deviation 2149.143 |
Secondary
Maximum Observed Serum Concentration (Cmax)
Time frame: Predose, 4 hours [hrs] postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12
Population: Pharmacokinetic (PK) analysis set included all participants who provided data for the estimation of at least 1 of the relevant PK parameters (Cmax, time to maximum concentration \[tmax\], area under the curve \[AUC\], terminal elimination half-life \[t1/2\], apparent systemic clearance \[CL/F\], and apparent volume of distribution \[Vz/F\]).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Serum Concentration (Cmax) | 4219.97 nanogram per milliliter (ng/mL) | Standard Deviation 945.23 |
| Bapineuzumab 5 mg | Maximum Observed Serum Concentration (Cmax) | 8012.88 nanogram per milliliter (ng/mL) | Standard Deviation 2793.53 |
Secondary
Serum Decay Half-Life (t1/2)
Serum decay half-life is the time measured for the serum concentration to decrease by one half.
Time frame: Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12
Population: t1/2 not calculated due to inadequate characterization of the terminal elimination phase.
Secondary
Time to Reach Maximum Observed Serum Concentration (Tmax)
Time frame: Predose, 4 hrs postdose, 72 hrs postdose on Day 3 of Week 0 and 25; Predose on Day 7 (Week 1), Week 10, 14, 16, 18, 22, 26, 30; Predose and 4 hrs postdose on Week 12
Population: PK analysis set included all participants who provided data for the estimation of at least 1 of the relevant PK parameters (Cmax, tmax, AUC, t1/2, CL/F and Vz/F).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Reach Maximum Observed Serum Concentration (Tmax) | 3696.00 hours |
| Bapineuzumab 5 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) | 4200.00 hours |