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

NCT00722046 | Completed Phase 2 Results DMC

• 3 other identifiers: A99510022008-000986-42MD IN AD PATIENT
• Study Type: interventional
• Target: 198
• Locations: 6 countries
• Sites: 42

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.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's disease; antibody; amyloid

Outcome Measures

Primary Outcomes (31)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Mean Plasma Concentration of PF-04360365 on Day 150

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

  Day 150

• 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

• 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

• Mean Plasma Concentration of PF-04360365 on Day 210

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

  Day 210

• 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

• 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

• 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

• 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

• 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

• 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

• Mean Plasma Concentration of PF-04360365 on Day 390

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

  Day 390

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Mean Plasma Concentration of PF-04360365 on Day 660

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

  Day 660

• Mean Plasma Concentration of PF-04360365 on Day 720

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

  Day 720

Secondary Outcomes (13)

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

  Baseline

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

  Baseline and Month 19

• Disability Assessment for Dementia (DAD) Score at Baseline

  Baseline

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

  Baseline and Month 19

• 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

Study Arms (6)

PF-04360365 0.1 mg/kg

EXPERIMENTAL

Biological: PF-04360365 0.1 mg/kg

PF-04360365 0.5 mg/kg

EXPERIMENTAL

Biological: PF-04360365 0.5 mg/kg

PF-04360365 1 mg/kg

EXPERIMENTAL

Biological: PF-04360365 1 mg/kg

Placebo

PLACEBO COMPARATOR

Drug: Placebo

PF-04360365 3 mg/kg

EXPERIMENTAL

Biological: PF-04360365 3 mg/kg

PF-04360365 8.5 mg/kg

EXPERIMENTAL

Biological: PF-04360365 8.5 mg/kg

Interventions

PF-04360365 0.1 mg/kg BIOLOGICAL

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

PF-04360365 0.1 mg/kg

PF-04360365 0.5 mg/kg BIOLOGICAL

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

PF-04360365 0.5 mg/kg

PF-04360365 1 mg/kg BIOLOGICAL

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

PF-04360365 1 mg/kg

Placebo DRUG

Placebo every 60 days (10 doses total)

Placebo

PF-04360365 3 mg/kg BIOLOGICAL

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

PF-04360365 3 mg/kg

PF-04360365 8.5 mg/kg BIOLOGICAL

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

PF-04360365 8.5 mg/kg

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 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

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 (42)

Pivotal Research Center

Peoria, Arizona, 85381, United States

Location

Sun Radiology- for MRI

Peoria, Arizona, 85381, United States

Location

Dedicated Phase 1

Phoenix, Arizona, 85013, United States

Location

Neuroscience Consultants, LLC

Miami, Florida, 33176, United States

Location

Miami Research Associates

South Miami, Florida, 33143, United States

Location

MRA Clinical Research

South Miami, Florida, 33143, United States

Location

Sleep Florida, LLC

South Miami, Florida, 33143, United States

Location

Alexian Brothers Medical Center

Elk Grove Village, Illinois, 60007, United States

Location

Alexian Brothers Neurosciences Institute

Elk Grove Village, Illinois, 60007, United States

Location

Stark Pharmacy

Overland Park, Kansas, 66209, United States

Location

Vince and Associates Clinical Research

Overland Park, Kansas, 66211, United States

Location

Vince and Associates Clinical Research

Overland Park, Kansas, 66212, United States

Location

Memory Enhancement Center of America, Inc

Eatontown, New Jersey, 07724, United States

Location

Central Jersey Radiology

Oakhurst, New Jersey, 07755, United States

Location

Butler Hospital

Providence, Rhode Island, 02906, United States

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Queen Elizabeth Hospital and Health Service

Woodville South, South Australia, 5011, Australia

Location

Heidelberg Repatriation Hospital, Austin Health

Heidelberg West, Victoria, 3084, Australia

Location

The McCusker Foundation for Alzheimer's Disease Research

Nedlands, Western Australia, 6009, Australia

Location

ZNA Middelheim / Neurology

Antwerp, 2020, Belgium

Location

UZ Antwerpen, Department of Neurology

Edegem, 2650, Belgium

Location

UZ Brussel / Geriatrie

Jette, 1090, Belgium

Location

U.Z. Gasthuisberg / Neurologie

Leuven, 3000, Belgium

Location

University of British Columbia Hospital, Division of Neurology

Vancouver, British Columbia, V6T 2B5, Canada

Location

Parkwood Hospital, Geriatric Medicine

London, Ontario, N6C 5J1, Canada

Location

Kawartha Regional Memory Clinic

Peterborough, Ontario, K9H 2P4, Canada

Location

Toronto Memory Program

Toronto, Ontario, M3B 2S7, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Recherche Clinique de Neurologie

Montreal, Quebec, H1T 2M4, Canada

Location

Diex Recherche Inc.

Sherbrooke, Quebec, J1H 1Z1, Canada

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 463-707, South Korea

Location

Hanyang University Hospital

Seoul, 133-792, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Korea University Anam Hospital

Seoul, 136-705, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Konkuk University Medical Center

Seoul, 143-914, South Korea

Location

The Pharmacy Department

Cheadle, Chesire, SK8 2PX, United Kingdom

Location

The Shalbourne Suite

Swindon, Wiltshire, SN3 6BB, United Kingdom

Location

Kingshill Research Centre

Swindon, Wiltshire, SN3 6BW, United Kingdom

Location

MAC UK Neuroscience Ltd

Manchester, M50 2GY, United Kingdom

Location

Wellcome Trust Clinical Research Facility

Southampton, SO16 6YD, United Kingdom

Location

Memory Assessment and Research Centre

Southampton, SO30 3JB, United Kingdom

Location

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

Limitations and Caveats

Data for CSF protein, RBCs, WBCs, and glucose was recorded as number of participants with laboratory test abnormalities and not as change from baseline values as planned.

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
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2008
• First Posted: July 25, 2008
• Study Start: December 5, 2008
• Primary Completion: August 16, 2011
• Study Completion: August 16, 2011
• Last Updated: November 7, 2022
• Results First Posted: November 7, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

US (15); BE (4); KR (6); CA (7); GB (6); AU (4)