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Completed

NCT Number: NCT00722046

Multiple IV Dose Study 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.

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Key information

Conditions

Alzheimer's Disease Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Royal Adelaide Hospital, Adelaide, South Australia, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

PF-04360365 0.1 mg/kg

Biological

0.1 mg/kg every 60 days (10 doses total)

PF-04360365 0.5 mg/kg

Biological

0.5 mg/kg every 60 days (10 doses total)

PF-04360365 1 mg/kg

Biological

1 mg/kg every 60 days (10 doses total)

Placebo

Drug

Placebo every 60 days (10 doses total)

PF-04360365 3 mg/kg

Biological

3 mg/kg every 60 days (10 doses total)

PF-04360365 8.5 mg/kg

Biological

8.5 mg/kg every 60 days (10 doses total)

Primary outcomes

  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 0 Hour on Day 0

    Only participants received PF-04360365 were analyzed for this outcome measure.

  5. Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 1

    Time frame: 0 Hour (pre-dose) on Day 1

    Only participants received PF-04360365 were analyzed for this outcome measure.

  6. Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 1

    Time frame: 2 Hours on Day 1

    Only participants received PF-04360365 were analyzed for this outcome measure.

  7. Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 60

    Time frame: 0 Hour (pre-dose) on Day 60

    Only participants received PF-04360365 were analyzed for this outcome measure.

  8. Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 60

    Time frame: 2 Hours on Day 60

    Only participants received PF-04360365 were analyzed for this outcome measure.

  9. Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 90

    Time frame: Day 90

    Only participants received PF-04360365 were analyzed for this outcome measure.

  10. Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 120

    Time frame: 0 Hour (pre-dose) on Day 120

    Only participants received PF-04360365 were analyzed for this outcome measure.

  11. Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 120

    Time frame: 2 Hours on Day 120

    Only participants received PF-04360365 were analyzed for this outcome measure.

  12. Mean Plasma Concentration of PF-04360365 on Day 150

    Time frame: Day 150

    Only participants received PF-04360365 were analyzed for this outcome measure.

  13. Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 180

    Time frame: 0 Hour (pre-dose) on Day 180

    Only participants received PF-04360365 were analyzed for this outcome measure.

  14. Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 180

    Time frame: 2 Hours on Day 180

    Only participants received PF-04360365 were analyzed for this outcome measure.

  15. Mean Plasma Concentration of PF-04360365 on Day 210

    Time frame: Day 210

    Only participants received PF-04360365 were analyzed for this outcome measure.

  16. Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 240

    Time frame: 0 Hour (pre-dose) on Day 240

    Only participants received PF-04360365 were analyzed for this outcome measure.

  17. Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 240

    Time frame: 2 Hours on Day 240

    Only participants received PF-04360365 were analyzed for this outcome measure.

  18. Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 300

    Time frame: 0 Hour (pre-dose) on Day 300

    Only participants received PF-04360365 were analyzed for this outcome measure.

  19. Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 300

    Time frame: 2 Hours on Day 300

    Only participants received PF-04360365 were analyzed for this outcome measure.

  20. Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 360

    Time frame: 0 Hour (pre-dose) on Day 360

    Only participants received PF-04360365 were analyzed for this outcome measure.

  21. Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 360

    Time frame: 2 Hours on Day 360

    Only participants received PF-04360365 were analyzed for this outcome measure.

  22. Mean Plasma Concentration of PF-04360365 on Day 390

    Time frame: Day 390

    Only participants received PF-04360365 were analyzed for this outcome measure.

  23. Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 420

    Time frame: 0 Hour (pre-dose) on Day 420

    Only participants received PF-04360365 were analyzed for this outcome measure.

  24. Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 420

    Time frame: 2 Hours on Day 420

    Only participants received PF-04360365 were analyzed for this outcome measure.

  25. Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 480

    Time frame: 0 Hour (pre-dose) on Day 480

    Only participants received PF-04360365 were analyzed for this outcome measure.

  26. Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 480

    Time frame: 2 Hours on Day 480

    Only participants received PF-04360365 were analyzed for this outcome measure.

  27. Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 540

    Time frame: 0 Hour (pre-dose) on Day 540

    Only participants received PF-04360365 were analyzed for this outcome measure.

  28. Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 540

    Time frame: 2 Hours on Day 540

    Only participants received PF-04360365 were analyzed for this outcome measure.

  29. Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 570

    Time frame: Day 570

    Only participants received PF-04360365 were analyzed for this outcome measure.

  30. Mean Plasma Concentration of PF-04360365 on Day 660

    Time frame: Day 660

    Only participants received PF-04360365 were analyzed for this outcome measure.

  31. Mean Plasma Concentration of PF-04360365 on Day 720

    Time frame: Day 720

    Only participants received PF-04360365 were analyzed for this outcome measure.

Secondary outcomes

  1. Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Baseline

    Time frame: 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.

  2. Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Month 19

    Time frame: 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.

  3. Disability Assessment for Dementia (DAD) Score at Baseline

    Time frame: 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.

  4. Change From Baseline in Disability Assessment for Dementia (DAD) Score at Month 19

    Time frame: 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.

  5. Mean Plasma Concentration of Amyloid Beta 1-x (Aβ1-x)

    Time frame: 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

  6. Mean Plasma Concentration of Amyloid Beta 1-40 (Aβ1-40)

    Time frame: 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

  7. Mean Plasma Concentration of Amyloid Beta 1-42 (Aβ1-42)

    Time frame: 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).

  8. Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (Aβ1-x)

    Time frame: Day 0 (Hour 0), 90, 570

  9. Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-40 (Aβ1-40)

    Time frame: Day 0 (Hour 0), 90, 570

  10. Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-42 (Aβ1-42)

    Time frame: Day 0 (Hour 0), 90, 570

  11. Mean Cerebrospinal Fluid (CSF) Concentration of Total Tau and Phospho-tau (P-tau)

    Time frame: Day 0 (Hour 0), 90, 570

  12. Number of Participants With Abnormal Cerebrospinal Fluid (CSF) Protein, Red Blood Cells (RBCs), White Blood Cells (WBCs), and Glucose Concentration

    Time frame: 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

  13. Number of Participants With Serum Anti-Drug Anti Body (ADA)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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.

Important dates

Study start
2008
Primary completion
2011
Study completion
2011
First posted
Jul 25, 2008
Registry last updated
Nov 7, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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