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    Summary
    EudraCT Number:2008-000327-25
    Sponsor's Protocol Code Number:A6341009
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2008-05-20
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2008-000327-25
    A.3Full title of the trial
    A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED,
    PARALLEL-GROUP STUDY OF CE-224,535, AN ANTAGONIST OF THE P2X7
    RECEPTOR, IN THE TREATMENT OF THE SIGNS AND SYMPTOMS OF
    RHEUMATOID ARTHRITIS IN SUBJECTS WHO ARE INADEQUATELY
    CONTROLLED ON METHOTREXATE
    A.4.1Sponsor's protocol code numberA6341009
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPfizer Inc. 235 East 42nd Street NY10017
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameCE-224,535
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 724424-43-5
    D.3.9.2Current sponsor codeCE-224,535
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125 mg
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Rheumatoid Arthritis
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10039073
    E.1.2Term Rheumatoid arthritis
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to test the efficacy of CE-224,535 vs placebo as
    assessed by the American College of Rheumatology 20 (ACR 20) Response Rate at 12 weeks in RA subjects inadequately controlled on methotrexate (MTX).
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are:
    1. To evaluate the safety and tolerability of CE-224,535 in subjects with active RA on a background of MTX.
    2. To evaluate health and functional status.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
    1. Any adult at least 18 years of age at Screening;
    2. A diagnosis of RA based upon the American College of Rheumatology 1987 Revised
    Criteria. The subject has a diagnosis of RA based upon the American College of
    Rheumatology, ie, fulfilling at least 4 of the following 7 criteria, for at least 6 consecutive months preceding participation:
    • Morning stiffness in and around any joint for more than 1 hour;
    • Soft tissue swelling of 3 or more joint areas;
    • Swelling of the proximal interphalangeal (PIP), metacarpophalangeal (MCP), or
    wrist joints;
    • Symmetrical joint swelling;
    • Rheumatoid nodules;
    • Serum rheumatoid factor positive;
    • Radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints;
    3. Must have active disease at Screening despite ongoing methotrexate treatment
    defined as:
    • ≥4 tender/painful joints on motion (28 joint count);
    • ≥4 swollen joints (28 joint count).
    4. Regarding MTX treatment, subjects must comply with all of the following criteria:
    • Receiving ≥7.5 /week (oral or parenteral) for the last 3 months;
    • No interruption >2 weeks during the same 3-month period;
    • Has received a stable dose for at least 4 weeks prior to Screening; and
    • No expected MTX dose change for the 12-week treatment duration.
    • Concomitant therapy with folic acid in a minimum of 400 mcg daily (or
    equivalent dosing on a less-than daily schedule) or folinic acid once weekly in
    locally approved doses (typically 5 mg, 24 hrs after the methotrexate dose).
    5. Other permitted DMARDS are: 1) Sulfasalazine at a dosage which has been stable for at least 8 weeks at randomization and does not exceed a total daily dose of 3 grams.
    2) Leflunomide at a dosage which has been stable for at least 4 weeks at
    randomization and does not exceed 20 mg daily (with the exception of a loading dose of up to 100 mg daily for 3 days at the initiation of therapy). 3) injectable or oral
    (auranofin) gold in locally approved doses, stable for at least 8 weeks prior to
    randomization 4) d-penicillamine in locally approved doses, stable for at least
    8 weeks prior to randomization, 5) chloroquine or hyrdoxychloroquine in locally
    approved doses, if it has been at a stable dose for at least 1 year prior to
    randomization with no history of anti-malarial related retinal toxicity. NO MORE
    THAN 2 OF THESE DMARDS, IN ADDITION TO METHOTREAXTE, MAY BE
    GIVEN DURING THE TRIAL OR FOR AT LEAST 1 MONTH PRIOR TO
    RANDOMIZATION.
    6. Meets ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II,or III
    7. Must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures; and
    8. Must provide written informed consent.
    E.4Principal exclusion criteria
    1. A diagnosis of any other inflammatory arthritis (eg, spondyloarthropathies) or
    secondary, noninflammatory arthritis (eg, osteoarthritis, fibromyalgia) that, in the
    opinion of the Investigator, would interfere with assessments for this trial.
    2. 12-lead ECG demonstrating QTc >460 msec for males and >480 msec for females at Screening;
    3. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception from at least 14 days prior to the first dose of trial medication until completion of follow-up procedures. Subjects who will remain on MTX after study completion should avoid pregnancy since MTX can
    cause birth defects.
    4. Subjects who have received the following prior treatments:
    • Within prior 4 weeks of Randomization: Herbal supplements*, corticosteroids by
    any route with the exception of a stabilized oral dose of ≤10 mg of prednisone or
    equivalent/day [which is allowed], azathioprine, cyclosporine, anakrina
    (Kineret®), etanercept (Enbrel®)
    • *Herbal supplements should be handled as follows: 1)Fish oil, flaxseed oil,
    borage oil, evening primrose oil, and inert substances such as
    glucosamine/chondroitin, as well as vitamin supplements may be continued as
    long as doses have been stable for one month prior to randomization 2) Known
    pharmacologically active herbal supplements such as St. John’s wort, red yeast
    rice, etc. or those with unknown/poorly studied activity are excluded ;
    • Within prior 8 weeks of Randomization: Infliximab (Remicade®), adalimumab
    (Humira®);
    • Within prior 8 weeks of Randomization: Any experimental therapy for RA
    (within or outside a clinical trial); with the exception of experimental
    NSAID/COX-2 inhibitors or opioids for which a washout interval of not less than
    5 half-lives shall apply. (Note: This excludes aspirin ≤325 mg/day for
    nonarthritic reasons provided the dose has been continuous and stable for at least
    2 weeks prior to the first dose of study medication.);
    • Within prior 3 months of Randomization: abatacept (Orencia®);
    • Within prior 12 months of Randomization: rituximab (Rituxan®); Such subjects
    must also demonstrate normal CD 20+ lymphocyte counts.
    5. Subjects who take lithium or warfarin within 1 month of randomization;
    6. Subjects who take concomitant medications that are CYP3A4 inhibitors or CYP3A4
    inducers (Appendix 1);
    7. Subjects who take opioid analgesics at a dose of >30 mg oral morphine or
    equivalent/day;
    8. Any retinal abnormalities noted during ophthalmoscopic examination at Screening;
    9. Subjects with a clinical diagnosis of glaucoma or other diseases affecting the
    posterior segment of the eye such as choroiditis, retinitis, chorioretinitis, uveitis,
    diabetic proliferative retinopathy, or diabetic macular edema; or any subject with
    significant cataracts or other eye pathology which restricts the ability to view the
    retina with ophthalmoscopy;
    10. Any condition possibly affecting oral drug absorption (eg, gastrectomy or clinically
    significant diabetic gastroenteropathy); Bariatric procedures (such as banding) that
    effectively divide the stomach but do not affect digestive/absorptive surface area of
    the stomach or intestines are NOT exclusionary;
    11. Tuberculosis without treatment and/or positive tuberculin reaction by PPD test
    without known history of vaccination with the Bacillus Calmette-Guérin (BCG)
    vaccine [only in subjects whose last BCG was ≤50 years prior to screening who do
    not have locally-defined risk factors for TB other than RA or its treatment]; A
    Quantiferon Gold Test, where locally available, may be substituted for a PPD.
    Treatment may be initiated up to 3 weeks prior to randomization, with express
    permission/discussion of the individual case with the Pfizer study team;
    12. Current evidence or history of acute myocardial infarction or of having undergone
    angioplasty or coronary bypass within 6 months prior to Screening;
    13. Subjects who currently have cancer or have been in remission for less than 5 years or had cancer with metastases beyond the local region of the primary tumor. This criterion does not apply to subjects with nonmetastatic basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ, who are eligible after 1 month of adequate treatment;
    14. Subjects determined to be homozygous for the C allele at RS_3751143 at Screening;
    15. Subjects unwilling to consent to non-anonymized pharmacogenomic analysis of the P2X7 receptor for screening purposes;
    16. Subjects who have participated in previous CE-224,535 trials;
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the ACR 20 Responder Rate at Week 12.
    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 No
    E.6.7Pharmacodynamic No
    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.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Yes
    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
    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 months1
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 35
    F.4.2.2In the whole clinical trial 78
    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 Decision2008-06-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-05-15
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2009-02-03
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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