Clinical trial NCT01821118: Study Evaluating the Safety,Tolerability and Efficacy of PF-04360365 in Adults With Probable Cerebral Amyloid Angiopathy
Official title: A Phase 2, Randomized, Double Blind Placebo Controlled Trial To Evaluate The Safety, Tolerability, Pharmacokinetics And Efficacy Of Pf-04360365 (Ponezumab) In Adult Subjects With Probable Cerebral Amyloid Angiopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cerebral Amyloid Angiopathy
Keywords: Cerebral amyloid angiopathy (CAA)
cerebrovascular reactivity
functional MRI
randomized
double blind
safety
efficacy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-03-29
Enrollment: 36
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Cerebral Amyloid Angiopathy (CAA) is a condition caused by the build-up of a protein called amyloid, predominantly Aβ40, within the walls of brain blood vessels, especially those blood vessels in the occipital lobe of the brain. Probable CAA may be defined as two or more hemorrhages in the brain cortex in individuals 55 years of age or older. This study will examine the study drug (PF-04360365) vs. placebo (saline) at 10 mg/kg - Day 1 and the maintenance dose of the study drug (PF-04360365) vs. placebo (saline) at 7.5mg/kg on Days 30 and 60. Subjects will be followed for 6 months after receiving the last dose of study medication.


Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with probable CAA using the Boston criteria; with no clinical cognitive impairment
* In general good health

Exclusion Criteria:

* Co-morbid diagnosis of clinically documented Alzheimer's disease or significant cognitive impairment
* Clinically significant syncope, epilepsy, head trauma or clinically significant unexplained loss of consciousness within the last 5 years
* Subject's body weight exceeding 100kg
* Women of childbearing potential.

Primary outcomes:
measure: 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)
timeFrame: Baseline, Day 2
measure: Change From Baseline to Day 90 in Cerebrovascular Reactivity as Measured by the Slope (Amplitude Over Time to Peak) From Visual Task-evoked fMRI
timeFrame: Baseline, Day 90
Secondary outcomes:
measure: Change From Baseline to Day 2 and Day 90 in Cerebrovascular Reactivity as Measured by the Time to Peak From Visual Task-evoked fMRI
timeFrame: Baseline, Day 2, Day 90
measure: Change From Baseline to Day 2 and Day 90 in Cerebrovascular Reactivity as Measured by the Amplitude From Visual Task-evoked fMRI
timeFrame: Baseline, Day 2, Day 90
measure: 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
timeFrame: Baseline, Day 2, Day 90
measure: Change From Baseline in Concentration of Total Plasma Amyloid Beta (AB)
timeFrame: Baseline, 8 hours post dose on Day 1, Day 2, Day 30, 90 and 240
measure: Number of Participants With Brain Structural Magnetic Resonance Imaging (sMRI) Abnormalities
timeFrame: Baseline/Screening, Day 15, Day 45, Day 90,
measure: Mean Montreal Cognitive Assessment (MoCA) Total Score Over Time
timeFrame: Screening; Days 0, 1, 30, 60, 90, and 240
measure: 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)
timeFrame: Baseline up to Day 240
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline up to Day 240
measure: Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria
timeFrame: Baseline up to Day 240
measure: Overall Number of Participants With Positive Responses to Questions on the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to Day 240
measure: Number of Participants With Significant Changes From Baseline in Physical Examination at Final Visit
timeFrame: Baseline up to Final Visit (Day 240)
measure: Number of Participants With Significant Changes in Neurological Examination Results
timeFrame: Baseline up till Day 240
measure: Number of Participants With Anti-PF-04360365 Antibodies
timeFrame: Day 1 up to Day 240
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Ronald Reagan Medical Center
state: California
city: Boston
country: United States
facility: MGH Stroke Research Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center - Menino Pavilion
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center - Shapiro Center
state: Massachusetts
city: Charlestown
country: United States
facility: Anthinoula A. Martinos Center for Biomedical Imaging
state: Massachusetts
city: St. Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: Calgary
country: Canada
facility: University of Calgary/Foothills Medical Centre
state: Alberta
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Lille Cedex
country: France
facility: CHRU de Lille - Hôpital Roger Salengro
state: NAP
city: Lille Cedex
country: France
facility: CHRU de Lille
state: NAP
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: London
country: United Kingdom
facility: University College of London
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: