A Multiple Dose Study of PF-04360365 In Patients With Mild to Moderate Alzheimer's Disease

Pfizer36 enrolled

Overview

The purpose of this study is to determine whether multiple dose administration is safe and well tolerated in patients with mild to moderate Alzheimer's Disease.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Alzheimer's Disease

Interventions

PF-04360365 10 mg/kgBIOLOGICAL

10 mg/kg every 90 days (5 total doses)

PF-04360365 7.5 mg/kgBIOLOGICAL

10 mg/kg loading dose followed by 7.5 mg/kg monthly maintenance dosing (total of 13 doses)

placeboDRUG

placebo administered every 90 days or monthly to match experimental treatment arms.

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Males or females of non childbearing potential, age \> or = 50. * Diagnosis of probable Alzheimer's disease, consistent with criteria from both: * National Institute of Neurological and Communicable Disease and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). * Diagnostic and Statistical Manual of Mental Disorders (DSM IV). * Mini-mental status exam score of 16-26 inclusive. * Rosen-Modified Hachinski Ischemia Score of \< or = 4. Exclusion Criteria: * Diagnosis or history of other demential or neurodegenerative disorders. * Diagnosis or history of clinically significant cerebrovascular disease. * Specific findings on magnetic resonance imaging (MRI); cortical infarct, micro hemorrhage, multiple white matter lacunes, extensive white matter abnormalities. * History of autoimmune disorders. * History of allergic or anaphylactic reactions.

Locations (4)

Sahlgrenska Sjukhuset, CTC

Gothenburg, Sweden

Malmo Sjukhus, Neuropsykiatriska Kliniken

Malmö, Sweden

Sahlgrenska Universitetssjukhuset, Minnesmottagningen

Mölndal, Sweden

Karolinska Universitetssjukhuset Huddinge

Stockholm, Sweden

Outcomes

Primary Outcomes

Number of Participants With Treatment-emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of 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 are events between first dose of study medication and up to 6 months after last dose (up to 18 months) that were absent before treatment or worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.

Time frame: Day 1 up to 6 months after last dose of study medication (up to 18 months)

Number of Participants With Change From Baseline in Brain Magnetic Resonance Imaging (MRI) Abnormalities

Number of participants with new clinical findings not evident on the baseline scans, such as brain edema, hemorrhage, encephalitis and other pathology (cerebral edema, cerebral/meningeal enhancement, micro hemorrhage, parenchymal hematoma, subarachnoid hemorrhage, subdural hematoma, cortical infarcts, subcortical grey matter infarcts, white matter infarcts and white matter hyper intensities) were assessed from structural magnetic resonance imaging (MRI). Participants with brain abnormality other than those listed above assessed using MRI scan were reported under 'other' category. Only those MRI findings in which at least 1 participant had event, were reported.

Time frame: Baseline up to Month 18

Number of Participants With Gadolinium Use in Brain Magnetic Resonance Imaging (MRI)

Brain MRI included gadolinium contrast if investigator determined this was necessary for participant care either based on clinical signs or the non-contrast MRI. This decision was made by the investigator on the basis of change in the clinical examination or in response to a possible abnormality seen on the non-contrast brain MRI.

Time frame: Baseline up to Month 18

Change From Baseline in Amyloid Load at Month 13 Using Positron Emission Tomography (PET) Technique: Cohort M

Data from ClinicalTrials.gov

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Quantitative amyloid imaging was performed using PET technique using \[11C\] Pittsburgh Compound B (PIB) for following brain areas: frontal, temporal, parietal and occipital cortices, anterior and posterior cingular cortex, cerebellum, pons, and subcortical white matter. For target regions of interest, beta-amyloid plaque imaging radiotracer (PIB) retention data was expressed as standard uptake value ratio (SUVR) which was defined as a ratio of radioactivity uptake of the target region relative to the cerebellum reference region. This outcome measure was planned to be analyzed only for cohort M.

Time frame: Baseline, Month 13

Mean Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 0