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

Phase 2

Completed

• Conditions: Alzheimer's Disease
• Interventions: 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; Biological: PF-04360365 0.1 mg/kg

• Registration Number: NCT00722046
• Lead Sponsor: Pfizer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-07-23
• Study First Submitted QC: 2008-07-24
• Study First Posted: 2008-07-25
• Study Start: 2008-12-05
• Primary Completion: 2011-08-16
• Study Completion: 2011-08-16
• Disposition First Submitted: 2012-10-08
• Disposition First Submitted QC: 2012-10-08
• Disposition First Posted: 2012-10-11
• Status Verified: 2022-10
• Results First Submitted: 2022-10-11
• Results First Submitted QC: 2022-10-11
• Last Update Submitted: 2022-10-11
• Results First Posted: 2022-11-07
• Last Update Posted: 2022-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 198

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PF-04360365 0.5 mg/kg	PF-04360365 0.5 mg/kg	-
PF-04360365 1 mg/kg	PF-04360365 1 mg/kg	-
Placebo	Placebo	-
PF-04360365 3 mg/kg	PF-04360365 3 mg/kg	-
PF-04360365 8.5 mg/kg	PF-04360365 8.5 mg/kg	-
PF-04360365 0.1 mg/kg	PF-04360365 0.1 mg/kg	-

Primary Outcome Measures

Name	Time	Method
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 60	0 Hour (pre-dose) on Day 60	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 90	Day 90	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 on Day 150	Day 150	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 240	2 Hours on Day 240	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 300	0 Hour (pre-dose) on Day 300	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 300	2 Hours on Day 300	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 360	0 Hour (pre-dose) on Day 360	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 360	2 Hours on Day 360	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 60	2 Hours on Day 60	Only participants received PF-04360365 were analyzed for this outcome measure.
Number of Participants With Gadolinium Use in Brain Magnetic Resonance Imaging (MRI)	Baseline up to Month 24	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.
Mean Plasma Concentration of PF-04360365 on Day 210	Day 210	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 240	0 Hour (pre-dose) on Day 240	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 on Day 660	Day 660	Only participants received PF-04360365 were analyzed for this outcome measure.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	Day 1 up to 6 months after last dose of study medication, assessed up to Month 24	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.
Number of Participants With Change From Baseline in Brain Magnetic Resonance Imaging (MRI) Abnormalities	Baseline up to Month 24	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.
Mean Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 0	0 Hour on Day 0	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 1	0 Hour (pre-dose) on Day 1	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 1	2 Hours on Day 1	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 120	0 Hour (pre-dose) on Day 120	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 120	2 Hours on Day 120	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 180	0 Hour (pre-dose) on Day 180	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 180	2 Hours on Day 180	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 on Day 390	Day 390	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 420	0 Hour (pre-dose) on Day 420	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 420	2 Hours on Day 420	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 480	0 Hour (pre-dose) on Day 480	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 480	2 Hours on Day 480	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 540	0 Hour (pre-dose) on Day 540	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 540	2 Hours on Day 540	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 570	Day 570	Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 on Day 720	Day 720	Only participants received PF-04360365 were analyzed for this outcome measure.

Secondary Outcome Measures

Name	Time	Method
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)	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	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).
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	Baseline up to Month 24	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
Number of Participants With Serum Anti-Drug Anti Body (ADA)	Day 1 up to Month 24	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.
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Baseline	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.
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Month 19	Baseline and 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.
Disability Assessment for Dementia (DAD) Score at Baseline	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.
Change From Baseline in Disability Assessment for Dementia (DAD) Score at Month 19	Baseline and 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.
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

Trial Locations

Locations (41)

The Shalbourne Suite; 🇬🇧 Swindon, Wiltshire, United Kingdom

Kingshill Research Centre; 🇬🇧 Swindon, Wiltshire, United Kingdom

Dedicated Phase 1; 🇺🇸 Phoenix, Arizona, United States

Toronto Memory Program; 🇨🇦 Toronto, Ontario, Canada

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

Wellcome Trust Clinical Research Facility; 🇬🇧 Southampton, United Kingdom

Neuroscience Consultants, LLC; 🇺🇸 Miami, Florida, United States

Pivotal Research Center; 🇺🇸 Peoria, Arizona, United States

Sun Radiology- for MRI; 🇺🇸 Peoria, Arizona, United States

Alexian Brothers Medical Center; 🇺🇸 Elk Grove Village, Illinois, United States

Kawartha Regional Memory Clinic; 🇨🇦 Peterborough, Ontario, Canada

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Central Jersey Radiology; 🇺🇸 Oakhurst, New Jersey, United States

ZNA Middelheim / Neurology; 🇧🇪 Antwerpen, Belgium

Heidelberg Repatriation Hospital, Austin Health; 🇦🇺 Heidelberg West, Victoria, Australia

UZ Antwerpen, Department of Neurology; 🇧🇪 Edegem, Belgium

Recherche Clinique de Neurologie; 🇨🇦 Montreal, Quebec, Canada

Hanyang University Hospital; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Seongnam, Gyeonggi, Korea, Republic of

Diex Recherche Inc.; 🇨🇦 Sherbrooke, Quebec, Canada

The Pharmacy Department; 🇬🇧 Cheadle, Chesire, United Kingdom

Parkwood Hospital, Geriatric Medicine; 🇨🇦 London, Ontario, Canada

Konkuk University Medical Center; 🇰🇷 Seoul, Korea, Republic of

Sleep Florida, LLC; 🇺🇸 South Miami, Florida, United States

Stark Pharmacy; 🇺🇸 Overland Park, Kansas, United States

MRA Clinical Research; 🇺🇸 South Miami, Florida, United States

Vince and Associates Clinical Research; 🇺🇸 Overland Park, Kansas, United States

Miami Research Associates; 🇺🇸 South Miami, Florida, United States

Alexian Brothers Neurosciences Institute; 🇺🇸 Elk Grove Village, Illinois, United States

The McCusker Foundation for Alzheimer's Disease Research; 🇦🇺 Nedlands, Western Australia, Australia

Butler Hospital; 🇺🇸 Providence, Rhode Island, United States

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

UZ Brussel / Geriatrie; 🇧🇪 Jette, Belgium

U.Z. Gasthuisberg / Neurologie; 🇧🇪 Leuven, Belgium

University of British Columbia Hospital, Division of Neurology; 🇨🇦 Vancouver, British Columbia, Canada

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Memory Assessment and Research Centre; 🇬🇧 Southampton, United Kingdom

MAC UK Neuroscience Ltd; 🇬🇧 Manchester, United Kingdom

Memory Enhancement Center of America, Inc; 🇺🇸 Eatontown, New Jersey, United States

The Queen Elizabeth Hospital and Health Service; 🇦🇺 Woodville South, South Australia, Australia