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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00722046




Registration number
NCT00722046
Ethics application status
Date submitted
23/07/2008
Date registered
25/07/2008
Date last updated
7/11/2022

Titles & IDs
Public title
Multiple IV Dose Study Of PF-04360365 In Patients With Mild To Moderate Alzheimer's Disease
Scientific 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.
Secondary ID [1] 0 0
2008-000986-42
Secondary ID [2] 0 0
A9951002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - PF-04360365 0.1 mg/kg
Treatment: Other - PF-04360365 0.5 mg/kg
Treatment: Other - PF-04360365 1 mg/kg
Treatment: Drugs - Placebo
Treatment: Other - PF-04360365 3 mg/kg
Treatment: Other - PF-04360365 8.5 mg/kg

Experimental: PF-04360365 0.1 mg/kg -

Experimental: PF-04360365 0.5 mg/kg -

Experimental: PF-04360365 1 mg/kg -

Placebo comparator: Placebo -

Experimental: PF-04360365 3 mg/kg -

Experimental: PF-04360365 8.5 mg/kg -


Treatment: Other: PF-04360365 0.1 mg/kg
0.1 mg/kg every 60 days (10 doses total)

Treatment: Other: PF-04360365 0.5 mg/kg
0.5 mg/kg every 60 days (10 doses total)

Treatment: Other: PF-04360365 1 mg/kg
1 mg/kg every 60 days (10 doses total)

Treatment: Drugs: Placebo
Placebo every 60 days (10 doses total)

Treatment: Other: PF-04360365 3 mg/kg
3 mg/kg every 60 days (10 doses total)

Treatment: Other: PF-04360365 8.5 mg/kg
8.5 mg/kg every 60 days (10 doses total)
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Day 1 up to 6 months after last dose of study medication, assessed up to Month 24
Primary outcome [2] 0 0
Number of Participants With Change From Baseline in Brain Magnetic Resonance Imaging (MRI) Abnormalities
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Baseline up to Month 24
Primary outcome [3] 0 0
Number of Participants With Gadolinium Use in Brain Magnetic Resonance Imaging (MRI)
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
Baseline up to Month 24
Primary outcome [4] 0 0
Mean Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 0
Assessment method [4] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [4] 0 0
0 Hour on Day 0
Primary outcome [5] 0 0
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 1
Assessment method [5] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [5] 0 0
0 Hour (pre-dose) on Day 1
Primary outcome [6] 0 0
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 1
Assessment method [6] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [6] 0 0
2 Hours on Day 1
Primary outcome [7] 0 0
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 60
Assessment method [7] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [7] 0 0
0 Hour (pre-dose) on Day 60
Primary outcome [8] 0 0
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 60
Assessment method [8] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [8] 0 0
2 Hours on Day 60
Primary outcome [9] 0 0
Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 90
Assessment method [9] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [9] 0 0
Day 90
Primary outcome [10] 0 0
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 120
Assessment method [10] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [10] 0 0
0 Hour (pre-dose) on Day 120
Primary outcome [11] 0 0
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 120
Assessment method [11] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [11] 0 0
2 Hours on Day 120
Primary outcome [12] 0 0
Mean Plasma Concentration of PF-04360365 on Day 150
Assessment method [12] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [12] 0 0
Day 150
Primary outcome [13] 0 0
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 180
Assessment method [13] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [13] 0 0
0 Hour (pre-dose) on Day 180
Primary outcome [14] 0 0
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 180
Assessment method [14] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [14] 0 0
2 Hours on Day 180
Primary outcome [15] 0 0
Mean Plasma Concentration of PF-04360365 on Day 210
Assessment method [15] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [15] 0 0
Day 210
Primary outcome [16] 0 0
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 240
Assessment method [16] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [16] 0 0
0 Hour (pre-dose) on Day 240
Primary outcome [17] 0 0
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 240
Assessment method [17] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [17] 0 0
2 Hours on Day 240
Primary outcome [18] 0 0
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 300
Assessment method [18] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [18] 0 0
0 Hour (pre-dose) on Day 300
Primary outcome [19] 0 0
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 300
Assessment method [19] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [19] 0 0
2 Hours on Day 300
Primary outcome [20] 0 0
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 360
Assessment method [20] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [20] 0 0
0 Hour (pre-dose) on Day 360
Primary outcome [21] 0 0
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 360
Assessment method [21] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [21] 0 0
2 Hours on Day 360
Primary outcome [22] 0 0
Mean Plasma Concentration of PF-04360365 on Day 390
Assessment method [22] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [22] 0 0
Day 390
Primary outcome [23] 0 0
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 420
Assessment method [23] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [23] 0 0
0 Hour (pre-dose) on Day 420
Primary outcome [24] 0 0
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 420
Assessment method [24] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [24] 0 0
2 Hours on Day 420
Primary outcome [25] 0 0
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 480
Assessment method [25] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [25] 0 0
0 Hour (pre-dose) on Day 480
Primary outcome [26] 0 0
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 480
Assessment method [26] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [26] 0 0
2 Hours on Day 480
Primary outcome [27] 0 0
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 540
Assessment method [27] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [27] 0 0
0 Hour (pre-dose) on Day 540
Primary outcome [28] 0 0
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 540
Assessment method [28] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [28] 0 0
2 Hours on Day 540
Primary outcome [29] 0 0
Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 570
Assessment method [29] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [29] 0 0
Day 570
Primary outcome [30] 0 0
Mean Plasma Concentration of PF-04360365 on Day 660
Assessment method [30] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [30] 0 0
Day 660
Primary outcome [31] 0 0
Mean Plasma Concentration of PF-04360365 on Day 720
Assessment method [31] 0 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Timepoint [31] 0 0
Day 720
Secondary outcome [1] 0 0
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Baseline
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Baseline
Secondary outcome [2] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Month 19
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Baseline and Month 19
Secondary outcome [3] 0 0
Disability Assessment for Dementia (DAD) Score at Baseline
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
Baseline
Secondary outcome [4] 0 0
Change From Baseline in Disability Assessment for Dementia (DAD) Score at Month 19
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Baseline and Month 19
Secondary outcome [5] 0 0
Mean Plasma Concentration of Amyloid Beta 1-x (Aß1-x)
Assessment method [5] 0 0
Timepoint [5] 0 0
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 outcome [6] 0 0
Mean Plasma Concentration of Amyloid Beta 1-40 (Aß1-40)
Assessment method [6] 0 0
Timepoint [6] 0 0
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 outcome [7] 0 0
Mean Plasma Concentration of Amyloid Beta 1-42 (Aß1-42)
Assessment method [7] 0 0
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).
Timepoint [7] 0 0
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 outcome [8] 0 0
Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (Aß1-x)
Assessment method [8] 0 0
Timepoint [8] 0 0
Day 0 (Hour 0), 90, 570
Secondary outcome [9] 0 0
Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-40 (Aß1-40)
Assessment method [9] 0 0
Timepoint [9] 0 0
Day 0 (Hour 0), 90, 570
Secondary outcome [10] 0 0
Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-42 (Aß1-42)
Assessment method [10] 0 0
Timepoint [10] 0 0
Day 0 (Hour 0), 90, 570
Secondary outcome [11] 0 0
Mean Cerebrospinal Fluid (CSF) Concentration of Total Tau and Phospho-tau (P-tau)
Assessment method [11] 0 0
Timepoint [11] 0 0
Day 0 (Hour 0), 90, 570
Secondary outcome [12] 0 0
Number of Participants With Abnormal Cerebrospinal Fluid (CSF) Protein, Red Blood Cells (RBCs), White Blood Cells (WBCs), and Glucose Concentration
Assessment method [12] 0 0
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
Timepoint [12] 0 0
Baseline up to Month 24
Secondary outcome [13] 0 0
Number of Participants With Serum Anti-Drug Anti Body (ADA)
Assessment method [13] 0 0
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.
Timepoint [13] 0 0
Day 1 up to Month 24

Eligibility
Key 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
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/12/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/08/2011
Sample size
Target
Accrual to date
Final
198
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital and Health Service - Woodville South
Recruitment hospital [3] 0 0
Heidelberg Repatriation Hospital, Austin Health - Heidelberg West
Recruitment hospital [4] 0 0
The McCusker Foundation for Alzheimer's Disease Research - Nedlands
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg West
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
Rhode Island
Country [7] 0 0
Belgium
State/province [7] 0 0
Antwerpen
Country [8] 0 0
Belgium
State/province [8] 0 0
Edegem
Country [9] 0 0
Belgium
State/province [9] 0 0
Jette
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Canada
State/province [11] 0 0
British Columbia
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Gyeonggi
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Chesire
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Wiltshire
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Manchester
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00722046