A PHASE 2 DOUBLE-BLINDED, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER STUDY EVALUATING THE SAFETY, TOLERABILITY AND PHARMACOKINETICS/ PHARMACODYNAMICS OF PF-04360365 IN MILD TO MODERATE ALZHEIMER’S DISEASE PATIENTS

• Register: EUCTR
• Last refreshed on: 29 April 2013
• Main ID: EUCTR2009-011172-30-SE
• Date of registration: 01/06/2009
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public title: A PHASE 2 DOUBLE-BLINDED, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER STUDY EVALUATING THE SAFETY, TOLERABILITY AND PHARMACOKINETICS/ PHARMACODYNAMICS OF PF-04360365 IN MILD TO MODERATE ALZHEIMER’S DISEASE PATIENTS
• Scientific title: A PHASE 2 DOUBLE-BLINDED, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER STUDY EVALUATING THE SAFETY, TOLERABILITY AND PHARMACOKINETICS/ PHARMACODYNAMICS OF PF-04360365 IN MILD TO MODERATE ALZHEIMER’S DISEASE PATIENTS
• Date of first enrolment: 10/08/2009
• Target sample size: 36
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011172-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: yes Other:

Countries of recruitment

Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males and females (of non-childbearing potential) ages =50 years of age at screening
2. Diagnosis of probable AD, consistent with criteria from both:
- NINCDS-Alzheimer’s Disease and Related Disorders Association (ADRDA);
- DSM-IV-TR
3. The subject must have a reliable caregiver with contact at least 3 times per week (combination of face to face visits and telephone contact acceptable) who will facilitate the subject’s full participation in the study. Caregivers must have sufficient subject interaction to be able to provide meaningful input into the DAD
4. Subjects and caregivers must be able to read, write, and speak the language in which psychometric tests are provided with acceptable visual and auditory acuity
5. MMSE score of 16–26 inclusive at screening
6. Rosen-Modified Hachinski Ischemia Score =4
7. Subjects must be on a stable dose of background cholinesterase inhibitor and/or memantine at least 60 days prior to dosing, with the following caveats: background cholinesterase inhibitor and/or memantine therapy is not required if the subject had previously demonstrated a lack of toleration
8. Subjects must weigh 35-100 kg
9. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) and caregiver have been informed of all pertinent aspects of the trial. Subject must be able to provide assent and assent may be re-evaluated during the study at regular intervals
10. Subjects and caregivers are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
11. Diabetic subjects may be included provided that their disease and serum glucose values are controlled and being actively managed, as assessed by the PI using a fasting blood sugar and/or HgA1C (per the PI’s medical judgment for diabetics)
12. In general good health, in the opinion of the Principal Investigator (PI), based on medical history, physical examination, vital signs, 12-lead ECG, and laboratory values, including hematology and chemistry values
13. Cohort M only - Subjects receiving amyloid imaging (PET) must have measurable amyloid burden on the screening brain PET scan with radiotracer retention in the range expected for AD patients. This will be defined as 3 of the 5 target regions (anterior cingulate, posterior cingulate, frontal cortex, temporal cortex, and parietal cortex) having a ratio of target region radioactivity (kBq/ml) over reference region radioactivity (cerebellar grey matter) >1.5. Subjects that do not have measurable amyloid burden will be excluded
14. Cohort M only - Subjects with a previous brain PET scan may be eligible to enter the study provided that the subject does not exceed the required local and/or national radiation exposure requirements
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Known presenilin mutations
2. Diagnosis or history of other possible cause for or significant contributor to dementia
3. Diagnosis or history of cerebrovascular disease, severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage, or subdural hematoma that could either contribute to the subject’s current cognitive or functional status, impair their ability to fully participate in the trial or that may impact their status during the two year trial
4. Specific exclusionary brain MRI findings that could either contribute to the subject’s current cognitive or functional decline, impair their ability to fully participate in the trial or that may impact their status during the one year course of the trial including:
- Cortical infarct;
- >2 micro hemorrhages;
- Strategically located subcortical gray matter infarct
- Multiple (2 or more) white matter lacunes
5. History or diagnosis of an underlying hematological disorder causing easy bruising
6. History or symptoms of a serious autoimmune disorder
7. History of cancer within the last 5 years
8. History of clinically significant cardiac arrhythmia or heart block
9. History or diagnosis of clinically significant ischemic heart disease, congestive heart failure, cardiomyopathy, myocarditis, left ventricular hypertrophy, valvular heart disease
10. History of clinically significant renal disease
11. Subjects with uncontrolled hypertension even with therapeutic intervention
(=170/100)
13. History of clinically significant syncope, seizure, head trauma, or clinically significant unexplained loss of consciousness within the last 5 years
14. A diagnosis of major depressive disorder or other psychiatric illness as the primary diagnosis
16. Known history of alcohol or drug abuse within 5 years prior to dosing or a positive result as a result of illicit drugs on the drug screening test
17. History of hospital admission within the last 2 years for asthma, chronic obstructive pulmonary disease, or other chronic respiratory conditions
18. Known positive HIV status
19. Subjects who reside in a nursing home or that are inpatients in a hospital; assisted living facilities are permitted
20. Subjects who are unable to participate in a successful baseline lumbar puncture and sample obtained
21. Subjects on anticoagulants or aspirin doses >325 mg/day within the last month. Plavix® (clopidogrel bisulfate) or aspirin may be discontinued per the PI’s medical judgment 3 -7 days prior to lumbar puncture
22. Previous exposure to investigational or non-investigational immune- or biologic therapies for Alzheimer’s disease such as anti-A ß antibodies, or ß- or gamma-secretase inhibitors.
23. Known allergy or sensitivity to gadolinium (or similar) contrast agents or PIB ligand that will affect the subject’s participation in this clinical trial or any device/implant/condition that would contraindicate a brain MRI or PET scan.
24. History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody or IgG-fusion protein.
25. Medications that may negatively affect cognitive function
26. Subjects cannot participate in other clinical drug trials for the duration of the study or donate blood within 8 weeks prior to the first infusion and for 6 months after the last administration of study drug.
27. History of sensitivity to heparin or heparin-induced thrombocytopenia.
28. Clinically significant laboratory abnormalities
29. Screening creatinine clearance of <30

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mild to Moderate Alzheimer's Disease
MedDRA version: 9.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease

Intervention(s)

Product Code: PF-04360365
Pharmaceutical Form: Intravenous infusion
Current Sponsor code: PF-04360365
Other descriptive name: RN 1219
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): 1. Safety endpoints will include adverse events, physical/neurological exams, vital signs, 12-lead ECG, clinical laboratory values (including CSF labs), brain MRI, immunogenicity and cognitive assessments

2. Change from baseline in amyloid load as assessed by positron emission tomography (PET) imaging at Month 13 in a subset of subjects (Cohort M)

3. Plasma and CSF concentrations (as available) of PF-04360365

4. CSF concentrations of Aß species.

Main Objective: 1. To evaluate safety, tolerability and pharmacokinetics of multiple doses of
PF-04360365 administered monthly (approximately every 30 days; Cohort M) or every 3 months (approximately every 90 days; Cohort Q) for approximately one year in subjects with mild-to-moderate AD.

2. To assess the effect of multiple doses of PF-04360365 on brain amyloid burden in the subjects dosed monthly (Cohort M) for approximately one year in subjects with mild-to-moderate AD.

3. To characterize the effect of PF-04360365 on CSF Aß during dosing for approximately one year.

Secondary Objective: 1. To examine the efficacy of PF-04360365, as assessed by the 70 point Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog), the Disability Assessment for Dementia (DAD) scales, and the Mini Mental State Examination (MMSE) in subjects with mild-to-moderate AD during and following dosing for approximately one year.

2. To examine the effect of PF-04350365 on plasma Aß species during and following dosing for approximately one year.

Secondary ID(s)

A9951007