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.

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2008-000986-42-FR
• Date of registration: 04/06/2009
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public 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.
• 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.
• Date of first enrolment: 23/07/2009
• Target sample size: 175
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000986-42
• 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: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet the following inclusion criteria to be eligible for study entry:

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 CDR/CDR-SB, NPI, and 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. Additionally, although strongly encouraged, background therapy is not mandatory for a world region where it is not the standard of care;

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. Women of non child-bearing potential defined as defined in the Lifestyle Guidelines;

12. Diabetic patients 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 PIs medical judgment for diabetics);

13. 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.
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:
Subjects who meet any of the following exclusion criteria will be ineligible for study entry.
Exclusions Related to AD
1. known presenilin mutations in subject or in the family that may account for dementia.
2. Diagnosis or history of other possible cause for or significant contributor to dementia,
3. Diagnosis or history of cerebrovascular, severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage, or subdural hematoma that could either contribute to the patient’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 patient’s current cognitive or functional decline, impair their ability to fully participate in the trial or that may impact their status during the two year course of the trial including:
Exclusions Related to General Health
1. Women of childbearing potential.
2. diagnosis of major depressive disorder or other psychiatric illness as the primary diagnosis.
3. History or symptoms of autoimmune disorders
4. History of cancer within the last 5 years (except for cutaneous basal cell, squamous cell cancer resolved by excision, or non-progressive prostate cancer).
5. History of clinically significant cardiac arrhythmia or heart block
6. History or diagnosis of clinically significant ischemic heart disease, congestive heart failure, cardiomyopathy, myocarditis, left ventricular hypertrophy, valvular heart disease.
7. History of clinically significant renal disease
8. Subjects with uncontrolled hypertension even with therapeutic intervention (=160/100).
9. History of clinically significant syncope, seizure, head trauma, or clinically significant unexplained loss of consciousness within the last 5 years.
10. Known history of alcohol or drug abuse (as defined by the DSM-IV-TR) within
5 years prior to dosing or a positive result as a result of illicit drugs on the drug +screening test.
11. Known positive HIV status.
12. Subjects who reside in a nursing home or that are inpatients in a hospital; assisted
living facilities are permitted.
Exclusions Related to Medications or Procedures
1. Any contraindications to the MRI procedure based on local operating procedures and instructions.
2. Previous exposure to investigational or non-investigational immune- or biologic therapies for Alzheimer’s
3. History of allergic or anaphylactic reaction to any therapeutic or diagnostic
monoclonal antibody or IgG-fusion protein.
4. Use of any of the disallowed concomitant medications within the excluded time periods.
5. Medications that may negatively affect cognitive function
6. Subjects cannot participate in other clinical drug trials for the duration of the study.
Subject may not donate blood within 8 weeks prior to the first infusion and for 6 months after the last administration of study drug.
Exclusions Related to Findings on Screening Tests
1. Clinically significant laboratory abnormalities in the opinion of the investigator or
Sponsor.
2. Screening creatinine clearance of <30 mL/min for AD subjects.
3. Active infection with hepatitis B or C.
4. Positive syphilis test, confirmed.
5. A clinically significant (as determined by the PI) abnormality in the 12-lead ECG,
6. Vitamin B12 levels lower than normal limits (and remains below on repeat testing).
Subjects may be enrolled following the initiation of B12 therapy for 4 weeks prior

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: 10-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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) and Disability Assessment for Dementia (DAD) scales, in subjects with mild-to-moderate AD;

2. To determine the effect of PF-04360365 on the following biochemical markers:
Aß species in CSF and plasma; CSF tau and phosphotau levels;

3. To examine the effect of PF-04360365 on CSF safety labs in the subset of subjects receiving lumbar punctures;

4. To determine the immunogenicity of PF-04360365 following repeat dosing;

5. To evaluate the PK/PD relationships for Aß biomarkers, ADAS-cog, DAD and
ECG.

Primary end point(s): Primary Endpoints:

1. Safety endpoints will include adverse events, physical/neurological exams, vital signs, 12-lead ECG, clinical laboratory values, brain MRI and cognitive assessments;

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

Main Objective: 1. To examine the safety and tolerability of PF-04360365 in subjects with mild-tomoderate
AD dosed for 18 months and followed for a total of 24 months;
2. To characterize the pharmacokinetics of PF-04360365 following administration of
multiple doses in subjects with mild-to-moderate AD.

Secondary ID(s)

A9951002

2008-000986-42-GB

Ethics review

Status: Approved
Approval date: 08/07/2009
Contact:

Results

• Results available: Yes
• Date Posted: 03/08/2016
• Date Completed: 16/08/2011
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-000986-42/results