A Multiple Dose Study of PF-04360365 In Patients With Mild to Moderate Alzheimer's Disease

NCT00945672 | Completed Phase 2 Results DMC

• 3 other identifiers: A99510072009-011172-30PIB/PET IMAGING
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to determine whether multiple dose administration is safe and well tolerated in patients with mild to moderate Alzheimer's Disease.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's disease amyloid imaging antibody

Outcome Measures

Primary Outcomes (50)

• 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 are events between first dose of study medication and up to 6 months after last dose (up to 18 months) that were absent before treatment or worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.

  Day 1 up to 6 months after last dose of study medication (up to 18 months)

• 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 edema, cerebral/meningeal enhancement, micro hemorrhage, parenchymal hematoma, subarachnoid hemorrhage, subdural hematoma, cortical infarcts, subcortical grey matter infarcts, white matter infarcts and white matter hyper intensities) were assessed from structural magnetic resonance imaging (MRI). Participants with brain abnormality other than those listed above assessed using MRI scan were reported under 'other' category. Only those MRI findings in which at least 1 participant had event, were reported.

  Baseline up to Month 18

• 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 up to Month 18

• Change From Baseline in Amyloid Load at Month 13 Using Positron Emission Tomography (PET) Technique: Cohort M

  Quantitative amyloid imaging was performed using PET technique using \[11C\] Pittsburgh Compound B (PIB) for following brain areas: frontal, temporal, parietal and occipital cortices, anterior and posterior cingular cortex, cerebellum, pons, and subcortical white matter. For target regions of interest, beta-amyloid plaque imaging radiotracer (PIB) retention data was expressed as standard uptake value ratio (SUVR) which was defined as a ratio of radioactivity uptake of the target region relative to the cerebellum reference region. This outcome measure was planned to be analyzed only for cohort M.

  Baseline, Month 13

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

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour on Day 0 (Day prior to dosing)

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

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 1

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 1

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 1

• Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 10: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  216 hours post dose on Day 1 (samples taken on Day 10)

• Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 20: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  456 hours post dose on Day 1 (samples taken on Day 20)

• Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 30: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 30

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 30: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 30

• Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 40: Cohort Q

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  936 hours post dose on Day 1 (samples taken on Day 40)

• Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 50: Cohort Q

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  1176 hours post dose on Day 1 (samples taken on Day 50)

• Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 60: Cohort Q

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  1416 hours post-dose on Day 1 (samples taken on Day 60)

• Mean Plasma Concentration of PF-04360365 at 0 Hours on Day 60: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 60

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 60: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 60

• Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 90

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 90

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 90

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 90

• Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 120: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 120

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 120: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 120

• Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 150: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 150

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 150: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 150

• Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 180

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 180

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 180

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 180

• Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 210: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 210

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 210: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 210

• Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 240: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 240

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 240: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 240

• Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 270

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 270

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 270

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 270

• Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 300: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 300

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 300: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 300

• Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 330: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 330

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 330: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 330

• Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 360

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 360

• Mean Plasma Concentration of PF-04360365 at 0.25 Hours on Day 360

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0.25 hours post-infusion start on Day 360

• Mean Plasma Concentration of PF-04360365 at 720 Hours Post-dose on Day 360: Cohort Q

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  720 hours post-dose on Day 360 (samples taken on Day 390)

• Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 390: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 390

• Mean Plasma Concentration of PF-04360365 at 0 Hours on Day 540: Cohort Q

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hours (pre-dose) on Day 540

• Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 540: Cohort M

  Samples for PF-04360365 concentration were assayed using a validated, sensitive and specific enzyme-linked immunosorbent assay method.

  0 hour (pre-dose) on Day 540

• Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 0 Hour on Day 0

  A-beta is a peptide fragment of the amyloid precursor protein (found in the brain of participants suffering from of Alzheimer's disease (AD). In this outcome, CSF concentration of 3 variants of A-beta were reported: A-beta (1-X), A-beta (1-40) and A-beta (1-42).

  0 hour on Day 0 (Day prior to dosing)

• Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 216 Hours Post-dose on Day 1: Cohort M

  216 hours post-dose on Day 1

• Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 456 Hours Post-dose on Day 1: Cohort M

  456 hours post-dose on Day 1

• Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 0 Hour on Day 30: Cohort M

  0 hour (pre-dose) on Day 30

• Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 936 Hours Post-dose on Day 1: Cohort Q

  936 hours post-dose on Day 1 (Samples taken on Day 40)

• Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 1176 Hours Post-dose on Day 1: Cohort Q

  1176 hours post-dose on Day 1 (Samples taken on Day 50)

• Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 1416 Hours Post-dose on Day 1: Cohort Q

  1416 hours post-dose on Day 1 (Samples taken on Day 60)

• Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 0 Hour on Day 90: Cohort Q

  0 hour (pre-dose) on Day 90

• Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 0 Hour on Day 180

  0 hour (pre-dose) on Day 180

• Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (A-beta 1-x), Amyloid Beta 1-40 (A-beta 1-40) and Amyloid Beta 1-42 (A-beta 1-42) at 0 Hour on Day 360

  0 hour (pre-dose) on Day 360

Secondary Outcomes (6)

• Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Total Score at Months 3, 6, 9, 13 and 18

  Baseline, Month 3, 6, 9, 13, 18

• Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Month 6, 13 and 18

  Baseline, Month 6, 13, 18

• Change From Baseline in Mini-Mental State Examination (MMSE) Total Score at Month 13

  Baseline, Month 13

• Mean Plasma Concentration of Amyloid Beta 1-x (A-beta 1-x)

  Cohort M&Q: 0 hour(hr) & 0.25 hrs post dose (pd) on Day (D) 1,90,180,270,360, 0 hr pd on D 60,390; Cohort Q: 936,1176 hrs pd on D1(D 40,50); Cohort M: 216, 456 hrs pd on D1(D 10,20), 0.25 hrs pd on D 60, 0 hr & 0.25 hrs pd on D 30,120,150,210,240,300,330

• Mean Plasma Concentration of Amyloid Beta 1-40 (A-beta 1-40)

  Cohort M&Q: 0 hr & 0.25 hrs post dose(pd) on Day(D) 1,90,180,270,360, 0 hr pd on D 60,390,540; Cohort Q: 936, 1176 hrs pd on D1(D 40,50); Cohort M: 216, 456 hrs pd on D1(D 10,20), 0.25 hrs pd on D60, 0 hr & 0.25 hrs pd on D 30,120,150,210, 240,300,330

Other Outcomes (5)

• Mean Cerebrospinal Fluid (CSF) Concentration of Total Tau and Phospho-tau (P-tau) Proteins

  Cohort M&Q: Pre dose (0 hr) on Day 0, 0 hr post dose on Day 180, 360; Cohort Q: 936, 1176 hrs post dose on Day 1(Day 40,50), 0 hr post dose on Day 60, 90; Cohort M: 216, 456 hrs post dose on Day 1(Day 10, 20), 0 hr post dose on Day 30

• Change From Baseline in Cerebrospinal Fluid (CSF) Protein Concentration at Day 10, 20, 30, 40, 50, 60, 90, 180 and 360

  Cohort M&Q: Baseline, 0 hr post dose on Day 180, 360; Cohort Q: 936, 1176 hrs post dose on Day 1(Day 40,50), 0 hr post dose on Day 60, 90; Cohort M: 216, 456 hrs post dose on Day 1(Day 10, 20), 0 hr post dose on Day 30

• Change From Baseline in Red Blood Cells (RBCs) and White Blood Cells (WBCs) Concentration in Cerebrospinal Fluid (CSF) at Day 10, 20, 30, 40, 50, 60, 90, 180, 360

  Cohort M&Q: Baseline, 0 hr post dose on Day 180, 360; Cohort Q: 936, 1176 hrs post dose on Day 1(Day 40,50), 0 hr post dose on Day 60, 90; Cohort M: 216, 456 hrs post dose on Day 1(Day 10, 20), 0 hr post dose on Day 30

Study Arms (3)

PF-04360365 10 mg/kg

EXPERIMENTAL

Biological: PF-04360365 10 mg/kg

PF-04360365 7.5 mg/kg

EXPERIMENTAL

Biological: PF-04360365 7.5 mg/kg

placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

PF-04360365 10 mg/kg BIOLOGICAL

10 mg/kg every 90 days (5 total doses)

PF-04360365 10 mg/kg

PF-04360365 7.5 mg/kg BIOLOGICAL

10 mg/kg loading dose followed by 7.5 mg/kg monthly maintenance dosing (total of 13 doses)

PF-04360365 7.5 mg/kg

placebo DRUG

placebo administered every 90 days or monthly to match experimental treatment arms.

placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females of non childbearing potential, age \> or = 50.
• Diagnosis of probable Alzheimer's disease, consistent with criteria 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (4)

Sahlgrenska Sjukhuset, CTC

Gothenburg, 413 45, Sweden

Location

Malmo Sjukhus, Neuropsykiatriska Kliniken

Malmo, 205 02, Sweden

Location

Sahlgrenska Universitetssjukhuset, Minnesmottagningen

Mölndal, 431 41, Sweden

Location

Karolinska Universitetssjukhuset Huddinge

Stockholm, 141 86, Sweden

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Alzheimer Disease

Interventions

ponezumab

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2009
• First Posted: July 24, 2009
• Study Start: August 6, 2009
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: April 19, 2024
• Results First Posted: April 19, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share

Locations

SE (4)