Study Evaluating the Safety,Tolerability and Efficacy of PF-04360365 in Adults With Probable Cerebral Amyloid Angiopathy

Change From Baseline to Day 2 and Day 90 in Cerebrovascular Reactivity as Measured by the Time to Peak From Visual Task-evoked fMRI

BOLD fMRI was performed at Screening (Baseline) and on Days 2 and 90. During each of these sessions, BOLD fMRI images were acquired in rapid succession as a flashing radial black and white checkerboard was presented alternately with a gray screen. This well established visual stimulus is known to produce a reliable increase in BOLD fMRI signal within the visual cortex region of the occipital lobe. The time course of the BOLD fMRI signal was used to assess the vascular reactivity. Imaging sites also acquired cerebral blood flow data using ASL scans at Screening and on Days 2 and 90. A standard T1-weighted image was also acquired to aid image analysis. All efficacy scans were analyzed centrally. Geometric means are presented in the original scale and SEs are presented in log e scale.

Time frame: Baseline, Day 2, Day 90

Change From Baseline to Day 2 and Day 90 in Cerebrovascular Reactivity as Measured by the Amplitude From Visual Task-evoked fMRI

BOLD fMRI was performed at Screening (Baseline) and on Days 2 and 90. During each of these sessions, BOLD fMRI images were acquired in rapid succession as a flashing radial black and white checkerboard was presented alternately with a gray screen. This well established visual stimulus is known to produce a reliable increase in BOLD fMRI signal within the visual cortex region of the occipital lobe. The time course of the BOLD fMRI signal was used to assess the vascular reactivity. Imaging sites also acquired cerebral blood flow data using ASL scans at Screening and on Days 2 and 90. A standard T1-weighted image was also acquired to aid image analysis. All efficacy scans were analyzed centrally. All values are presented in log e scale.

Time frame: Baseline, Day 2, Day 90

Change From Baseline to Day 2 and Day 90 in Cerebrovascular Reactivity as Measured by the Time to Return to Baseline From Visual Task-evoked fMRI

BOLD fMRI was performed at Screening (Baseline) and on Days 2 and 90. During each of these sessions, BOLD fMRI images were acquired in rapid succession as a flashing radial black and white checkerboard was presented alternately with a gray screen. This well established visual stimulus is known to produce a reliable increase in BOLD fMRI signal within the visual cortex region of the occipital lobe. The time course of the BOLD fMRI signal was used to assess the vascular reactivity. Imaging sites also acquired cerebral blood flow data using ASL scans at Screening and on Days 2 and 90. A standard T1-weighted image was also acquired to aid image analysis. All efficacy scans were analyzed centrally. All values are presented in log e scale.

Time frame: Baseline, Day 2, Day 90

Change From Baseline in Concentration of Total Plasma Amyloid Beta (AB)

Cerebral amyloid angiopathy (CAA) is caused by the progressive deposition of amyloid, predominantly AB40, within the walls of cerebral blood vessels with a predisposition for the vessels of the occipital lobe. As such, it is of interest to investigate the effect of PF-04360365 on AB concentrations. AB1-x and AB1-40 were investigated.

Time frame: Baseline, 8 hours post dose on Day 1, Day 2, Day 30, 90 and 240

Number of Participants With Brain Structural Magnetic Resonance Imaging (sMRI) Abnormalities

Brain sMRI abnormalities included cerebral edema and total infarcts (including cortical infarcts, white matter infarcts, and subcortical gray matter infarcts). "Total infarcts" is the total number of participants with at least 1 type of infarct.

Time frame: Baseline/Screening, Day 15, Day 45, Day 90,

Mean Montreal Cognitive Assessment (MoCA) Total Score Over Time

The Montreal Cognitive Assessment (MoCA) was used as a safety outcome measure to assess any changes in cognition. The MoCA is a 1-page 30-point test administered in approximately 10 minutes. The MoCA assessed short term memory, visuospatial abilities, multiple aspects of executive functions, attention, concentration, working memory, and language, as well as orientation to time and place. The total scale ranges from 0 to 30, with lower numbers indicating lower cognition performance.

Time frame: Screening; Days 0, 1, 30, 60, 90, and 240

Number of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to Adverse Events (AEs)

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs comprised both SAEs and non-SAEs. 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 adverse events (TEAEs) were defined as newly occurring AEs or those worsening after first dose.

Time frame: Baseline up to Day 240

Number of Participants With Laboratory Abnormalities

Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, liver function (including Hy's Law Criteria), renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).

Time frame: Baseline up to Day 240

Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria

Categorical summarization criteria in vital signs included: supine systolic blood pressure (SBP) of less than (\<)90 millimeters of mercury (mm Hg) or more than (\>) 160 mm Hg; supine diastolic blood pressure (DBP) \<50 mm Hg or \>100 mm Hg; supine pulse rate of \<60 beats per minute (bpm) or \>100 bpm; maximum changes (increase or decrease) from baseline in supine SBP of \>=20 mm Hg; maximum increase from baseline in supine DBP of \>=20 mm Hg; and maximum decrease from baseline in supine DBP of \>=10 mm Hg.

Time frame: Baseline up to Day 240

Overall Number of Participants With Positive Responses to Questions on the Columbia Suicide Severity Rating Scale (C-SSRS)

C-SSRS assessed whether participant responded "yes" to the following: completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, self-injurious behavior with no suicidal intent.

Time frame: Baseline up to Day 240

Number of Participants With Significant Changes From Baseline in Physical Examination at Final Visit

A complete physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, skeletal, and neurological systems.

Time frame: Baseline up to Final Visit (Day 240)

Number of Participants With Significant Changes in Neurological Examination Results

A complete/full neurological examination included assessment of the cranial nerves; muscle strength, tone, cortical drift, abnormal movements; deep tendon reflexes; sensory exam, coordination, gait and station.

Time frame: Baseline up till Day 240

Number of Participants With Anti-PF-04360365 Antibodies

Blood samples were collected from participants who received active treatment to assess for presence/absence of anti-PF-04360365 antibodies.

Time frame: Day 1 up to Day 240