Multiple IV Dose Study Of PF-04360365 In Patients With Mild To Moderate Alzheimer's Disease

A PHASE 2 MULTICENTER, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY OF THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF MULTIPLE DOSES OF PF 04360365 IN PATIENTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE.

Purpose of the study is to determine whether multiple dose administration of PF-04360365 is safe and well tolerated in patient with mild to moderate Alzheimer's disease.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Biological: PF-04360365 0.1 mg/kg; Biological: PF-04360365 0.5 mg/kg; Biological: PF-04360365 1 mg/kg; Drug: Placebo; Biological: PF-04360365 3 mg/kg; Biological: PF-04360365 8.5 mg/kg

• Study Type: Interventional
• Enrollment (Actual): 198
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital and Health Service
  • Victoria
    • Heidelberg West, Victoria, Australia, 3084
      • Heidelberg Repatriation Hospital, Austin Health
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • The McCusker Foundation for Alzheimer's Disease Research
• Belgium
  • Antwerpen, Belgium, 2020
    • ZNA Middelheim / Neurology
  • Edegem, Belgium, 2650
    • UZ Antwerpen, Department of Neurology
  • Jette, Belgium, 1090
    • UZ Brussel / Geriatrie
  • Leuven, Belgium, 3000
    • U.Z. Gasthuisberg / Neurologie
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • University of British Columbia Hospital, Division of Neurology
  • Ontario
    • London, Ontario, Canada, N6C 5J1
      • Parkwood Hospital, Geriatric Medicine
    • Peterborough, Ontario, Canada, K9H 2P4
      • Kawartha Regional Memory Clinic
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Recherche Clinique de Neurologie
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • Diex Recherche Inc.
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung medical center
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 136-705
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 133-792
    • Hanyang University Hospital
  • Seoul, Korea, Republic of, 143-914
    • Konkuk University Medical Center
  • Gyeonggi
    • Seongnam, Gyeonggi, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital
• United Kingdom
  • Manchester, United Kingdom, M50 2GY
    • MAC UK Neuroscience Ltd
  • Southampton, United Kingdom, SO30 3JB
    • Memory Assessment and Research Centre
  • Southampton, United Kingdom, SO16 6YD
    • Wellcome Trust Clinical Research Facility
  • Chesire
    • Cheadle, Chesire, United Kingdom, SK8 2PX
      • The Pharmacy Department
  • Wiltshire
    • Swindon, Wiltshire, United Kingdom, SN3 6BB
      • The Shalbourne Suite
    • Swindon, Wiltshire, United Kingdom, SN3 6BW
      • Kingshill Research Centre
• United States
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Pivotal Research Center
    • Peoria, Arizona, United States, 85381
      • Sun Radiology- for MRI
    • Phoenix, Arizona, United States, 85013
      • Dedicated Phase 1
  • Florida
    • Miami, Florida, United States, 33176
      • Neuroscience Consultants, LLC
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • South Miami, Florida, United States, 33143
      • MRA Clinical Research
    • South Miami, Florida, United States, 33143
      • Sleep Florida, LLC
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Medical Center
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Neurosciences Institute
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research
    • Overland Park, Kansas, United States, 66209
      • Stark Pharmacy
    • Overland Park, Kansas, United States, 66211
      • Vince and Associates Clinical Research
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center of America, Inc
    • Oakhurst, New Jersey, United States, 07755
      • Central Jersey Radiology
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or females of non childbearing potential, age > or = 50

• Diagnosis of probable Alzheimer's disease, consistent with criterial 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo every 60 days (10 doses total)
Experimental: PF-04360365 8.5 mg/kg	Biological: PF-04360365 8.5 mg/kg; 8.5 mg/kg every 60 days (10 doses total)
Experimental: PF-04360365 1 mg/kg	Biological: PF-04360365 1 mg/kg; 1 mg/kg every 60 days (10 doses total)
Experimental: PF-04360365 3 mg/kg	Biological: PF-04360365 3 mg/kg; 3 mg/kg every 60 days (10 doses total)
Experimental: PF-04360365 0.1 mg/kg	Biological: PF-04360365 0.1 mg/kg; 0.1 mg/kg every 60 days (10 doses total)
Experimental: PF-04360365 0.5 mg/kg	Biological: PF-04360365 0.5 mg/kg; 0.5 mg/kg every 60 days (10 doses total)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 AEs are events between first dose of study medication and up to 6 months after last dose that were absent before treatment or worsened relative to pre-treatment state.	Day 1 up to 6 months after last dose of study medication, assessed up to Month 24
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/meningeal enhancement, parenchymal hematoma, subarachnoid hemorrhage, subdural hematoma, cortical infarcts, subcortical grey matter infarcts, white matter infarcts and white matter hyperintensities) were assessed from structural MRI. Participants with brain abnormality other than those listed above, assessed using MRI scan, were reported under other abnormality. Baseline was defined as the last assessment prior to the first study drug infusion.	Baseline up to Month 24
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. Baseline was defined as the last assessment prior to the first study drug infusion.	Baseline up to Month 24
Mean Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 0	Only participants received PF-04360365 were analyzed for this outcome measure.	0 Hour on Day 0
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 1	Only participants received PF-04360365 were analyzed for this outcome measure.	0 Hour (pre-dose) on Day 1
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 1	Only participants received PF-04360365 were analyzed for this outcome measure.	2 Hours on Day 1
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 60	Only participants received PF-04360365 were analyzed for this outcome measure.	0 Hour (pre-dose) on Day 60
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 60	Only participants received PF-04360365 were analyzed for this outcome measure.	2 Hours on Day 60
Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 90	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 90
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 120	Only participants received PF-04360365 were analyzed for this outcome measure.	0 Hour (pre-dose) on Day 120
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 120	Only participants received PF-04360365 were analyzed for this outcome measure.	2 Hours on Day 120
Mean Plasma Concentration of PF-04360365 on Day 150	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 150
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 180	Only participants received PF-04360365 were analyzed for this outcome measure.	0 Hour (pre-dose) on Day 180
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 180	Only participants received PF-04360365 were analyzed for this outcome measure.	2 Hours on Day 180
Mean Plasma Concentration of PF-04360365 on Day 210	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 210
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 240	Only participants received PF-04360365 were analyzed for this outcome measure.	0 Hour (pre-dose) on Day 240
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 240	Only participants received PF-04360365 were analyzed for this outcome measure.	2 Hours on Day 240
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 300	Only participants received PF-04360365 were analyzed for this outcome measure.	0 Hour (pre-dose) on Day 300
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 300	Only participants received PF-04360365 were analyzed for this outcome measure.	2 Hours on Day 300
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 360	Only participants received PF-04360365 were analyzed for this outcome measure.	0 Hour (pre-dose) on Day 360
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 360	Only participants received PF-04360365 were analyzed for this outcome measure.	2 Hours on Day 360
Mean Plasma Concentration of PF-04360365 on Day 390	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 390
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 420	Only participants received PF-04360365 were analyzed for this outcome measure.	0 Hour (pre-dose) on Day 420
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 420	Only participants received PF-04360365 were analyzed for this outcome measure.	2 Hours on Day 420
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 480	Only participants received PF-04360365 were analyzed for this outcome measure.	0 Hour (pre-dose) on Day 480
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 480	Only participants received PF-04360365 were analyzed for this outcome measure.	2 Hours on Day 480
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 540	Only participants received PF-04360365 were analyzed for this outcome measure.	0 Hour (pre-dose) on Day 540
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 540	Only participants received PF-04360365 were analyzed for this outcome measure.	2 Hours on Day 540
Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 570	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 570
Mean Plasma Concentration of PF-04360365 on Day 660	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 660
Mean Plasma Concentration of PF-04360365 on Day 720	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 720

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Baseline	ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's Disease. It comprised of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). ADAS-cog total score was calculated as the sum of scores for the 11 items and ranged from 0 to 70. Higher total and individual item scores indicate greater cognitive impairment. Baseline was defined as the last assessment prior to the first study drug infusion.	Baseline
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Month 19	ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's Disease. It comprised of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). ADAS-cog total score was calculated as the sum of scores for the 11 items and ranged from 0 to 70. Higher total and individual item scores indicate greater cognitive impairment. Baseline was defined as the last assessment prior to the first study drug infusion.	Baseline and Month 19
Disability Assessment for Dementia (DAD) Score at Baseline	DAD is a functional assessment based on interview with the caregiver. It consisted of 40 items, 17 related to self-care and 23 items involving instrumental activities of daily living. Each item was scored as yes = 1, no = 0 and not applicable= N/A. A total score was obtained by adding the rating for each question and converting this to a total score out of 100. The items rated N/A were not considered for the total score. DAD total score ranged from 0 to 100, with higher scores indicating better functioning. Baseline was defined as the last assessment prior to the first study drug infusion.	Baseline
Change From Baseline in Disability Assessment for Dementia (DAD) Score at Month 19	DAD is a functional assessment based on interview with the caregiver. It consisted of 40 items, 17 related to self-care and 23 items involving instrumental activities of daily living. Each item was scored as yes = 1, no = 0 and not applicable= N/A. A total score was obtained by adding the rating for each question and converting this to a total score out of 100. The items rated N/A were not considered for the total score. DAD total score ranged from 0 to 100, with higher scores indicating better functioning. Baseline was defined as the last assessment prior to the first study drug infusion.	Baseline and Month 19
Mean Plasma Concentration of Amyloid Beta 1-x (Aβ1-x)		0 Hour (pre-dose) and 2 hours on Day 1, 60, 120, 180, 240, 300, 360, 420, 480, 540; Day 90, 150, 210, 390, 570, 660, 720
Mean Plasma Concentration of Amyloid Beta 1-40 (Aβ1-40)		0 Hour (pre-dose) and 2 hours on Day 1, 60, 120, 180, 240, 300, 360, 420, 480, 540; Day 90, 150, 210, 390, 570, 660, 720
Mean Plasma Concentration of Amyloid Beta 1-42 (Aβ1-42)	Results are not reported for PF-04360365 0.1, 0.5, 1.0 mg/kg, Placebo (Part A and B) arms because plasma Aβ1-42 concentrations were sporadic and below the lower limit of quantification (20 pg/mL).	0 Hour (pre-dose) and 2 hours on Day 1, 60, 120, 180, 240, 300, 360, 420, 480, 540; Day 90, 150, 210, 390, 570, 660, 720
Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (Aβ1-x)		Day 0 (Hour 0), 90, 570
Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-40 (Aβ1-40)		Day 0 (Hour 0), 90, 570
Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-42 (Aβ1-42)		Day 0 (Hour 0), 90, 570
Mean Cerebrospinal Fluid (CSF) Concentration of Total Tau and Phospho-tau (P-tau)		Day 0 (Hour 0), 90, 570
Number of Participants With Abnormal Cerebrospinal Fluid (CSF) Protein, Red Blood Cells (RBCs), White Blood Cells (WBCs), and Glucose Concentration	Abnormality was defined as concentration either less than lower limit of normal (LLN) or more than upper limit of normal (ULN). Baseline was defined as the last assessment prior to the first study drug infusion	Baseline up to Month 24
Number of Participants With Serum Anti-Drug Anti Body (ADA)	Serum samples were analyzed for the presence or absence of anti-PF-04360365 antibodies using validated semi-quantitative enzyme linked immunosorbent assay (ELISA). Only participants receiving PF-04360365 were analyzed for this outcome measure.	Day 1 up to Month 24

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2008
• Primary Completion (Actual): August 16, 2011
• Study Completion (Actual): August 16, 2011

Study Registration Dates

• First Submitted: July 23, 2008
• First Submitted That Met QC Criteria: July 24, 2008
• First Posted (Estimate): July 25, 2008

Study Record Updates

• Last Update Posted (Actual): November 7, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: amyloid; Alzheimer's disease; antibody
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: A9951002; 2008-000986-42 (EudraCT Number); MD IN AD PATIENT (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.