A Phase 1, Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptive, Multiple Ascending Dose Study Of The Safety, Tolerability And Pharmacokinetics Of Aab-003 (Pf-05236812) In Subjects With Mild To Moderate Alzheimer's Disease

Number of Participants With Laboratory Abnormalities

时间窗: Baseline up to 39 Weeks and at Early Withdrawal

Number of Participants With Vital Signs of Potential Clinical Concern

时间窗: Baseline up to 39 Weeks and at Early Withdrawal

Criteria for potential clinical concern in vital signs included: supine/sitting pulse rate of less than (\<) 40 or more than (\>) 120 beats per minute (bpm), and standing pulse rate of \<40 or \>140 bpm; systolic blood pressure (SBP) of more than or equal to (\>=)30 millimeters of mercury (mm Hg) change from baseline in same posture and \<90 mm Hg; diastolic blood pressure (DBP) \>=20 mm Hg change from baseline in same posture and \<50 mm Hg. Only supine vital signs were planned for this study. Unplanned sitting vital signs were collected only in the 8/mg and placebo groups and also reported.

Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

时间窗: Baseline up to 39 Weeks and at Early Withdrawal

Number of Participants With Abnormal Neurological Examination Findings

时间窗: Screening, Day 1 (Baseline) and Weeks 1,6,13,19,26,32, and 39, and at Early Withdrawal

The neurological examination was done to the extent needed to assess the participant for any potential changes in neurological status, as determined by the investigator. The minimum items assessed were level of consciousness, speech, cranial nerves, motor, sensory, coordination, gait, and tendon reflexes.

Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.

Serum Decay Half-Life (t1/2) for AAB-003 at Week 26

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.

Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)

时间窗: Baseline up to Week 39 or Early Withdrawal

The C-SSRS assessed whether the participant experienced the following: completed suicide (1), suicide attempt (2) (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").

Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding

时间窗: Baseline up to Week 32.

Brain MRIs were collected during the course of study to assess for any potential drug-related changes that might have constituted a safety concern for study participants. Findings suggestive of either vasogenic edema (VE) or intracranial hemorrhage represented adverse events of special circumstance and were to be reported immediately.

Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit

时间窗: Day 1, Week 13, and Week 26

VE of the brain, identified via MRI, was identified as an adverse event of special circumstance.

Systemic Clearance (CL) for AAB-003 in Serum at Day 1

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.

Systemic Clearance (CL) for AAB-003 in Serum at Week 26

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.

Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.

Number of Participants With Abnormal Physical Examination Findings

时间窗: Baseline up to 39 Weeks and at Early Withdrawal

Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.

Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.

Serum Decay Half-Life (t1/2) for AAB-003 at Day 1

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.

Average Concentration (Cavg) for AAB-003 in Serum at Day 1

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.

Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.

Average Concentration (Cavg) for AAB-003 in Serum at Week 26

时间窗: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.

Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria

时间窗: Baseline, Weeks 1,13,16,26,39 or Early Withdrawal

Criteria for ECG values of potential clinical concern are: interval between the start of the ECG P wave and the start of the QRS complex corresponding to the time between onset of atrial depolarization and onset of ventricular depolarization (PR): \>= 300 milliseconds (msec), and \>=25% increase when baseline \>=200 msec/ \>=50% increase when baseline less than or equal to (\<=) 200 msec; time from ECG Q wave to the end of S wave corresponding to ventricular depolarization (QRS): \>=200 msec, and \>=25% increase when baseline \>100 msec/ \>=50% increase when baseline \<=100 msec; QTc using Fridericia's formula (QTcF) interval: 450 to \<480 msec, \>=480 msec; QTcF change from baseline: 30 to \<60 msec, and \>=60 msec.