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    The EU Clinical Trials Register currently displays   39182   clinical trials with a EudraCT protocol, of which   6421   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2013-001557-27
    Sponsor's Protocol Code Number:A9951024
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-06-11
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2013-001557-27
    A.3Full title of the trial
    A PHASE 2, RANDOMIZED, DOUBLE BLIND PLACEBO CONTROLLED TRIALTO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF PF-04360365 (PONEZUMAB) IN ADULT SUBJECTS WITH PROBABLE CEREBRAL AMYLOID ANGIOPATHY
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of Ponezumab in patients with probable Cerebral Amyloid Angiopathy
    A.4.1Sponsor's protocol code numberA9951024
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01821118
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPfizer Inc. 235 East 42nd Street, New York, NY 10017
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportPfizer Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPfizer Inc
    B.5.2Functional name of contact pointClinical Trials.gov Call Center
    B.5.3 Address:
    B.5.3.1Street Address235 East 42nd Street
    B.5.3.2Town/ cityNew York
    B.5.3.3Post codeNY 10017
    B.5.3.4CountryUnited States
    B.5.4Telephone number001 800 718 1021
    B.5.5Fax number001 303 739 1119
    B.5.6E-mailClinicalTrials.gov_Inquiries@pfizer.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePF-04360365
    D.3.2Product code PF-04360365
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPonezumab
    D.3.9.3Other descriptive namePF-04360365
    D.3.9.4EV Substance CodeSUB23634
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number250
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Cerebral Amyloid Angiopathy (CAA)
    E.1.1.1Medical condition in easily understood language
    Cerebral Amyloid Angiopathy: A disease of the blood vessels of the brain
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10068044
    E.1.2Term Cerebral amyloid angiopathy
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of PF-04360365 (ponezumab) in subjects with probable CAA as compared to placebo on a BOLD fMRI measure of cerebrovascular reactivity.
    E.2.2Secondary objectives of the trial
    Secondary Objectives:

    -To evaluate the efficacy of PF-04360365 (ponezumab) in subjects with probable CAA as compared to placebo on additional BOLD fMRI measures of cerebrovascular reactivity.

    - To evaluate the effect of PF-04360365 (ponezumab) in subjects with probable CAA as compared to placebo on changes in the concentration of total plasma Aβ.

    Exploratory Objective:
    To evaluate the effect of PF-04360365 (ponezumab) in subjects with probable CAA as compared to placebo on cerebral blood flow.

    Safety Objective:
    To evaluate the safety, tolerability and pharmacokinetics of PF-04360365 (ponezumab) to subjects with probable CAA.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Additional Pharmacogenomic Research (Optional),

    (Section 7.8.1.2 of the main study protocol)

    Subjects will be asked to indicate on the consent form whether they will allow the Retained Pharmacogenomic Sample(s) to also be used for the following additional research:

    - Investigations of the disease under study in the clinical trial, and related conditions.

    - Samples may be used as controls. This includes use in case -control studies of diseases for which Pfizer is researching drug therapies; use in characterizing the natural variation amongst people in genes, RNA, proteins, and metabolites; and use in developing new technologies related to pharmacogenomics.

    Subjects need not provide additional samples for the substudy the
    samples collected in the main study will be used.

    Subjects may still participate in the main study if they elect not to allow their Retained Pharmacogenomic Samples to be used for the additional purposes of the substudy.
    E.3Principal inclusion criteria
    1. Men, and women of non-childbearing potential between the ages of 55 and 90 years old who have the diagnosis of probable CAA using the Boston criteria and have an acceptable sMRI in the previous 12 months
    for review. Male subjects must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned drug. Female subjects who are not of childbearing
    potential (ie, meet at least one of the following criteria):
    - Have undergone a documented hysterectomy and/or bilateral oophorectomy;
    - Have medically confirmed ovarian failure; or
    - Are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; with laboratory confirmation (Serum
    follicle-stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females).

    2. CAA disease has not resulted in any meaningful clinical cognitive or functional deficit as documented by the PI in consultation with the sponsor.

    3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.

    4. Subjects are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

    5. 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.

    6. Subjects must have corrected vision at or better than 20/50 as assessed with a Snellen chart. If glasses are required to meet these criteria, they must be MRI-compliant glasses provided by the site.

    7. An acceptable screening fMRI that passes QC requirements.
    E.4Principal exclusion criteria
    1. Co-morbid diagnosis of clinically documented Alzheimer's disease or significant cognitive impairment.

    - A score of <26 on the MMSE.

    2. History of cancer within the last 5 years (except for cutaneous basal cell, squamous cell cancer resolved by excision, colon polyp resolved by excision, or non-progressive prostate cancer per investigator’s judgment).

    3. History of clinically significant (as determined by the PI) cardiac arrhythmia or heart block (eg sick sinus syndrome, ventricular tachycardia or fibrillation, sustained supraventricular tachycardia, symptomatic bradycardia, congenital long QT interval syndrome, atrial fibrillation).

    4. History or diagnosis of clinically significant (as determined by the PI) ischemic heart disease (eg, angina, clinically significant coronary artery disease, myocardial infarction in the past 2 years), congestive heart failure, cardiomyopathy, myocarditis, left ventricular hypertrophy, valvular heart disease.

    5. History of clinically significant (as determined by the PI) renal disease, such as glomerulonephritis, nephrotic syndrome, single kidney or polycystic kidney.

    6. Subjects with uncontrolled hypertension (≥170/100).

    7. History of clinically significant (as determined by the PI) syncope, head trauma, or clinically significant unexplained loss of consciousness within the last 5 years.

    8. History of photo-convulsive seizure, seizure disorder currently untreated or seizures in the past 18 months.

    9. A diagnosis of major depressive disorder or other psychiatric illness as the primary diagnosis per the DSM-IV TR criteria per the investigator’s judgment.

    10. History of schizophrenia, bipolar disorder, or other severe mental illness.

    11. 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.

    12. Known positive HIV status.

    13. Subjects who reside in a nursing home or that are inpatients in a hospital.

    14. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation orinvestigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

    15. Pregnant females; breastfeeding females; females of childbearing potential; males of childbearing potential not using highly effective contraception or not agreeing to use highly effective contraception for at least 28 days after last dose of investigational product.
    16. Subject's body weight cannot exceed 105 kg. No more than 3 subjects are to be enrolled with weight > 100 kg.

    Exclusions Related to Medications or Procedures

    1. Previous exposure to investigational or non-investigational immune- or biologic therapies for Alzheimer’s disease such as anti-Aβ antibodies, or β- or γ-secretase inhibitors.

    2. Any contraindications to MRI such as, but not limited to cardiac pacemaker; implanted cardiac defibrillator; aneurysm clips; carotid artery vascular clamp; neurostimulator; insulin or infusion pumps; implanted drug infusion device; bone growth/fusion stimulator; cochlear, otologic, ear implant; severe claustrophobia or requiring sedation; passive implants that may be weakly ferromagnetic in the vicinity of the RF coil that may cause image artifacts in the head scans; obesity or body habitus that exceeds MRI table weight limits or prevents subject from fitting into the scanner.

    3. History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody or IgG-fusion protein.

    4. Medications that may negatively affect cognitive function, such as anticholinergics (including agents with pronounced anticholinergic properties such as amitriptyline) with the following caveats:
    - Sedatives and tranquilizers (eg, benzodiazepine and nonbenzodiazepine hypnotics) used as a sleeping aid and taken routinely are allowable provided that subjects have been on a stable dose for at least 60 days prior to dosing, with no anticipated change during the study participation;
    - Anti-epileptic drugs for seizures or reasons other than seizures are permitted provided that subjects have been on a stable dose for at least 60 days prior to dosing, with no anticipated change during the study participation. Topiramate, phenytoin and barbiturates are excluded.

    5. The following medications are excluded if used from 1 month prior to the Screening visit through the end of the study:

    - Anti-coagulants;
    - Approved cognitive enhancers (cholinesterase inhibitors, memantine).

    6. The use of anti-inflammatory (NSAIDS and steroids) drugs prescribed specifically/solely for treatment of CAA (other stable use permitted).

    For exclusion criteria 7 and 8 Related to Medications or Procedures
    please refer to the protocol.

    E.5 End points
    E.5.1Primary end point(s)
    The change from baseline to Day 2 or Day 90 in cerebrovascular reactivity as measured by the slope (amplitude over time to peak) from visual task-evoked fMRI.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Screening visit, Visit 3, and Visit 8.
    E.5.2Secondary end point(s)
    Secondary Endpoints:

    1. The change from baseline to Day 2 or Day 90 in cerebrovascular reactivity as measured by the time to peak, magnitude, and time to baseline from visual task-evoked fMRI.

    2. The change from baseline of total plasma Aβ species at specified endpoints after the initial dose of study medication on the concentration.

    Exploratory Endpoint:

    The change from baseline to Day 2 or Day 90 on cerebral blood flow as measured by arterial spin labeling (ASL).

    Safety Endpoints:

    1. The change from baseline at specified time points on brain structural MRI following each dose of ponezumab: CMBs, VE, infarcts.

    2. The change from baseline at specified time points on the Montreal Cognitive Assessment (MoCA).

    3. Other safety endpoints include changes from baseline on C-SSRS, physical and neurological assessments, laboratory assessments, 12-lead ECG, vital signs, immunogenicity, AE monitoring.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Please refer to the schedule of assessments table in the protocol
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    France
    Netherlands
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months7
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 18
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 18
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 36
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    As per standard of care
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-08-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-01-13
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-09-23
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
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