Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT01821118
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01821118
Recruitment Status : Completed
First Posted : March 29, 2013
Results First Posted : November 3, 2016
Last Update Posted : May 10, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE March 4, 2013
First Posted Date  ICMJE March 29, 2013
Results First Submitted Date  ICMJE September 14, 2016
Results First Posted Date  ICMJE November 3, 2016
Last Update Posted Date May 10, 2017
Study Start Date  ICMJE June 2013
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2016)
  • 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) [ Time Frame: Baseline, Day 2 ]
    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.
  • Change From Baseline to Day 90 in Cerebrovascular Reactivity as Measured by the Slope (Amplitude Over Time to Peak) From Visual Task-evoked fMRI [ Time Frame: Baseline, Day 90 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 28, 2013)
Change from baseline to Day 2 or day 90 in cerebrovascular reactivity. [ Time Frame: screening +90 days ]
Change History Complete list of historical versions of study NCT01821118 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2017)
  • Change From Baseline to Day 2 and Day 90 in Cerebrovascular Reactivity as Measured by the Time to Peak From Visual Task-evoked fMRI [ Time Frame: Baseline, Day 2, Day 90 ]
    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.
  • Change From Baseline to Day 2 and Day 90 in Cerebrovascular Reactivity as Measured by the Amplitude From Visual Task-evoked fMRI [ Time Frame: Baseline, Day 2, Day 90 ]
    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.
  • 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 [ Time Frame: Baseline, Day 2, Day 90 ]
    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.
  • Change From Baseline in Concentration of Total Plasma Amyloid Beta (AB) [ Time Frame: Baseline, 8 hours post dose on Day 1, Day 2, Day 30, 90 and 240 ]
    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.
  • Number of Participants With Brain Structural Magnetic Resonance Imaging (sMRI) Abnormalities [ Time Frame: Baseline/Screening, Day 15, Day 45, Day 90, ]
    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.
  • Mean Montreal Cognitive Assessment (MoCA) Total Score Over Time [ Time Frame: Screening; Days 0, 1, 30, 60, 90, and 240 ]
    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.
  • 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) [ Time Frame: Baseline up to Day 240 ]
    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.
  • Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to Day 240 ]
    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).
  • Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria [ Time Frame: Baseline up to Day 240 ]
    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.
  • Overall Number of Participants With Positive Responses to Questions on the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline up to Day 240 ]
    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.
  • Number of Participants With Significant Changes From Baseline in Physical Examination at Final Visit [ Time Frame: Baseline up to Final Visit (Day 240) ]
    A complete physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, skeletal, and neurological systems.
  • Number of Participants With Significant Changes in Neurological Examination Results [ Time Frame: Baseline up till Day 240 ]
    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.
  • Number of Participants With Anti-PF-04360365 Antibodies [ Time Frame: Day 1 up to Day 240 ]
    Blood samples were collected from participants who received active treatment to assess for presence/absence of anti-PF-04360365 antibodies.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2013)
  • Change from baseline to Day 2 or Day 90 in cerebrovascular reactivity. [ Time Frame: screening +90 days ]
  • Change from baseline of total plasma AB species [ Time Frame: screening +240 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating the Safety,Tolerability and Efficacy of PF-04360365 in Adults With Probable Cerebral Amyloid Angiopathy
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cerebral Amyloid Angiopathy
Intervention  ICMJE
  • Biological: Ponezumab
    Infusion of Ponezumab (Day 1=10mg/kg; Day 30 and Day 60 dose = 7.5mg/kg) or placebo (saline); administered via infusion for a total infusion time of 20 minutes.
  • Other: placebo
    placebo (saline)- given via infusion total infusion time of 20 minutes
Study Arms  ICMJE
  • Experimental: 1
    Intervention: Biological: Ponezumab
  • Placebo Comparator: 2
    Intervention: Other: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 28, 2013)
36
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2015
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Netherlands,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01821118
Other Study ID Numbers  ICMJE A9951024
2013-001557-27 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP