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

NCT01821118 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: A99510242013-001557-27
• Study Type: interventional
• Target: 36
• Locations: 5 countries
• Sites: 13

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.

Conditions

Cerebral Amyloid Angiopathy

Keywords

Cerebral amyloid angiopathy (CAA); cerebrovascular reactivity; functional MRI; randomized; double blind; safety; efficacy

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline, Day 2

• 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.

  Baseline, Day 90

Secondary Outcomes (13)

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

  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

  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

  Baseline, Day 2, Day 90

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

  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

  Baseline/Screening, Day 15, Day 45, Day 90,

Study Arms (2)

1

EXPERIMENTAL

Biological: Ponezumab

2

PLACEBO COMPARATOR

Other: placebo

Interventions

Ponezumab BIOLOGICAL

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.

1

placebo OTHER

placebo (saline)- given via infusion total infusion time of 20 minutes

2

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (13)

UCLA Ronald Reagan Medical Center

Los Angeles, California, 90095, United States

Location

MGH Stroke Research Center

Boston, Massachusetts, 02114, United States

Location

Boston Medical Center - Menino Pavilion

Boston, Massachusetts, 02118, United States

Location

Boston Medical Center - Shapiro Center

Boston, Massachusetts, 02118, United States

Location

Anthinoula A. Martinos Center for Biomedical Imaging

Charlestown, Massachusetts, 02129, United States

Location

Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Calgary/Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

CHRU de Lille - Hôpital Roger Salengro

Lille, NAP, 59037, France

Location

CHRU de Lille

Lille, NAP, 59037, France

Location

University Medical Center Utrecht

Utrecht, Utrecht, 3584 CX, Netherlands

Location

University College of London

London, WC1N 3BG, United Kingdom

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Cerebral Amyloid Angiopathy

Interventions

ponezumab

Condition Hierarchy (Ancestors)

Cerebral Arterial Diseases; Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc

ClinicalTrials.gov_Inquiries@pfizer.com

18007181021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2013
• First Posted: March 29, 2013
• Study Start: June 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: May 10, 2017
• Results First Posted: November 3, 2016

Record last verified: 2017-04

Locations

US (7); CA (2); FR (2); NL (1); GB (1)