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

Alzheimer's Disease Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00722046
• Other study ID #: A9951002
• Secondary ID: 2008-000986-42MD
• Status: Completed
• Phase: Phase 2
• Start date: December 5, 2008
• Est. completion date: August 16, 2011

Study information

• Verified date: October 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 198
• Est. completion date: August 16, 2011
• Est. primary completion date: August 16, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Biological:
• PF-04360365 0.1 mg/kg
0.1 mg/kg every 60 days (10 doses total)
• PF-04360365 0.5 mg/kg
0.5 mg/kg every 60 days (10 doses total)
• PF-04360365 1 mg/kg
1 mg/kg every 60 days (10 doses total)

Drug:
• Placebo
Placebo every 60 days (10 doses total)

Biological:
• PF-04360365 3 mg/kg
3 mg/kg every 60 days (10 doses total)
• PF-04360365 8.5 mg/kg
8.5 mg/kg every 60 days (10 doses total)

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Heidelberg Repatriation Hospital, Austin Health	Heidelberg West	Victoria
Australia	The McCusker Foundation for Alzheimer's Disease Research	Nedlands	Western Australia
Australia	The Queen Elizabeth Hospital and Health Service	Woodville South	South Australia
Belgium	ZNA Middelheim / Neurology	Antwerpen
Belgium	UZ Antwerpen, Department of Neurology	Edegem
Belgium	UZ Brussel / Geriatrie	Jette
Belgium	U.Z. Gasthuisberg / Neurologie	Leuven
Canada	Parkwood Hospital, Geriatric Medicine	London	Ontario
Canada	Recherche Clinique de Neurologie	Montreal	Quebec
Canada	Kawartha Regional Memory Clinic	Peterborough	Ontario
Canada	Diex Recherche Inc.	Sherbrooke	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Toronto Memory Program	Toronto	Ontario
Canada	University of British Columbia Hospital, Division of Neurology	Vancouver	British Columbia
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Hanyang University Hospital	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
United Kingdom	The Pharmacy Department	Cheadle	Chesire
United Kingdom	MAC UK Neuroscience Ltd	Manchester
United Kingdom	Memory Assessment and Research Centre	Southampton
United Kingdom	Wellcome Trust Clinical Research Facility	Southampton
United Kingdom	Kingshill Research Centre	Swindon	Wiltshire
United Kingdom	The Shalbourne Suite	Swindon	Wiltshire
United States	Memory Enhancement Center of America, Inc	Eatontown	New Jersey
United States	Alexian Brothers Medical Center	Elk Grove Village	Illinois
United States	Alexian Brothers Neurosciences Institute	Elk Grove Village	Illinois
United States	Neuroscience Consultants, LLC	Miami	Florida
United States	Central Jersey Radiology	Oakhurst	New Jersey
United States	Stark Pharmacy	Overland Park	Kansas
United States	Vince and Associates Clinical Research	Overland Park	Kansas
United States	Vince and Associates Clinical Research	Overland Park	Kansas
United States	Pivotal Research Center	Peoria	Arizona
United States	Sun Radiology- for MRI	Peoria	Arizona
United States	Dedicated Phase 1	Phoenix	Arizona
United States	Butler Hospital	Providence	Rhode Island
United States	Miami Research Associates	South Miami	Florida
United States	MRA Clinical Research	South Miami	Florida
United States	Sleep Florida, LLC	South Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Mean Plasma Concentration of PF-04360365 on Day 150	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 150
Primary	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
Primary	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
Primary	Mean Plasma Concentration of PF-04360365 on Day 210	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 210
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Mean Plasma Concentration of PF-04360365 on Day 390	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 390
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Mean Plasma Concentration of PF-04360365 on Day 660	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 660
Primary	Mean Plasma Concentration of PF-04360365 on Day 720	Only participants received PF-04360365 were analyzed for this outcome measure.	Day 720
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mean Plasma Concentration of Amyloid Beta 1-x (Aß1-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
Secondary	Mean Plasma Concentration of Amyloid Beta 1-40 (Aß1-40)		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
Secondary	Mean Plasma Concentration of Amyloid Beta 1-42 (Aß1-42)	Results are not reported for PF-04360365 0.1, 0.5, 1.0 mg/kg, Placebo (Part A and B) arms because plasma Aß1-42 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
Secondary	Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (Aß1-x)		Day 0 (Hour 0), 90, 570
Secondary	Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-40 (Aß1-40)		Day 0 (Hour 0), 90, 570
Secondary	Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-42 (Aß1-42)		Day 0 (Hour 0), 90, 570
Secondary	Mean Cerebrospinal Fluid (CSF) Concentration of Total Tau and Phospho-tau (P-tau)		Day 0 (Hour 0), 90, 570
Secondary	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
Secondary	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