| Primary | Change From Baseline to Day 2 in Cerebrovascular Reactivity as Measured by the Slope (Amplitude Over Time to Peak) From Visual Task-evoked Functional Magnetic Resonance Imaging (fMRI) | Blood Oxygen Level Dependant (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 Arterial Spin Labeled (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 standard errors (SE) are presented in logarithmic (log e) scale. | The full analysis set (FAS) consisted of all participants who received at least 1 post-dose efficacy measurement. n=number of evaluable participants for the specified region of interest (ROI) at Day 2. | Posted | | Geometric Mean | Standard Error | percent/second | | Baseline, Day 2 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo | Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min. |
| | | Title | Denominators | Categories |
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| Region of interest (ROI) 1 (n=20, 11) | | | Title | Measurements |
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| - OG0000.954± 0.085
- OG0010.969± 0.073
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| | ROI2 (n=23, 11) | | |
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| ROI1: Analysis of the change from baseline in log(slope) was carried out using a Bayesian linear model (ANCOVA). Treatment was a fixed effect within the model and the log(slope) at baseline was included as a covariate. | | | | | Geometric Mean Ratio | 0.984 | Standard Error of the Mean | 0.112 | 2-Sided | 90 | 0.820 | 1.184 | | | SE of mean is presented in log e scale. | | Superiority or Other | | | |
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| Primary | Change From Baseline to Day 90 in Cerebrovascular Reactivity as Measured by the Slope (Amplitude Over 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. | The full analysis set (FAS) consisted of all participants who received at least 1 post-dose efficacy measurement. n=number of evaluable participants for the specified ROI at Day 90. | Posted | | Geometric Mean | Standard Error | percent/second | | Baseline, Day 90 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo |
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| Secondary | 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. | The full analysis set (FAS) consisted of all participants who received at least 1 post-dose efficacy measurement. n=number of evaluable participants for the specified ROI at the specified day. | Posted | | Geometric Mean | Standard Error | seconds | | Baseline, Day 2, Day 90 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo |
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| Secondary | 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. | The full analysis set (FAS) consisted of all participants who received at least 1 post-dose efficacy measurement. n=number of evaluable participants for the specified ROI at the specified day. | Posted | | Least Squares Mean | 90% Confidence Interval | percent | | Baseline, Day 2, Day 90 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo | |
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| Secondary | 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. | The full analysis set (FAS) consisted of all participants who received at least 1 post-dose efficacy measurement. n=number of evaluable participants for the specified ROI at the specified day. | Posted | | Least Squares Mean | 90% Confidence Interval | seconds | | Baseline, Day 2, Day 90 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo |
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| Secondary | 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. | All 36 participants who received study treatment were included in this pharmacodynamic analysis. n=number of participants with measurable AB at the specified time point. | Posted | | Mean | Standard Deviation | picograms (pg)/milliliter (mL) | | Baseline, 8 hours post dose on Day 1, Day 2, Day 30, 90 and 240 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo | Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min. |
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| Secondary | 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. | All 36 participants who received study treatment were analyzed for this endpoint. | Posted | | Number | | participants | | Baseline/Screening, Day 15, Day 45, Day 90, | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo | Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min. |
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| Secondary | 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. | All 36 participants who received study treatment were included in the analysis. On Day 240, the number of evaluable participants in the placebo group was 11 instead of 12. | Posted | | Mean | Standard Deviation | units on a scale | | Screening; Days 0, 1, 30, 60, 90, and 240 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo | Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min. |
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| Secondary | 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. | All 36 participants who received study drug were included in the AE summarization/analysis. | Posted | | Number | | participants | | Baseline up to Day 240 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo | Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min. |
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| Secondary | 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). | All 36 participants who received study drug were included in the analysis. | Posted | | Number | | participants | | Baseline up to Day 240 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo | Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min. |
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| Secondary | 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. | All 36 participants who received study drug were included in the analysis. | Posted | | Number | | participants | | Baseline up to Day 240 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo | Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min. |
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| Secondary | 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. | All 36 participants who received study drug were included in the analysis. | Posted | | Number | | participants | | Baseline up to Day 240 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo | Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min. |
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| Secondary | 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. | All 36 participants who received study drug were included in the analysis. | Posted | | Number | | participants | | Baseline up to Final Visit (Day 240) | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo | Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min. |
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| Secondary | 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. | All 36 participants who received study drug were included in the analysis. | Posted | | Number | | participants | | Baseline up till Day 240 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. | | OG001 | Placebo | Participants received a loading dose of placebo matching PF-04360365 10 mg/kg on Day 1, followed by placebo matching PF-04360365 7.5 mg/kg on Days 30 and 60. Placebo was also administered via IV infusion over a period of 10-15 min. |
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| Secondary | 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. | All 24 participants who received PF-04360365 were included in this analysis. | Posted | | Number | | participants | | Day 1 up to Day 240 | | | | ID | Title | Description |
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| OG000 | PF-04360365 | Participants received a loading dose of PF-04360365 10 milligrams (mg)/kilograms (kg) on Day 1, followed by PF-04360365 7.5 mg/kg on Days 30 and 60. PF-04360365 was administered via intravenous (IV) infusion over a period of 10-15 minutes (min) and dosing was based on participant weight. |
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