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    Summary
    EudraCT Number:2005-001889-13
    Sponsor's Protocol Code Number:P04249
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2006-04-20
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2005-001889-13
    A.3Full title of the trial
    Randomised controlled trial evaluating strategies to optimize disease activity control in RA patients treated with infliximab in clinical practice.
    A.3.2Name or abbreviated title of the trial where available
    RE3
    A.4.1Sponsor's protocol code numberP04249
    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 SponsorIntegrated Therapeutics Group, Inc. - A subsidiary of Schering-Plough Corp.
    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 Yes
    D.2.1.1.1Trade name Remicade
    D.2.1.1.2Name of the Marketing Authorisation holderCentocor B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    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) 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 Yes
    D.3.11.13.1Other medicinal product typemonoclonal antibody
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Adult subjects with a diganosis of Rheumatoid Arthritis presenting with a disease flare after an initial response to infliximab.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 8.1
    E.1.2Level LLT
    E.1.2Classification code 10060732
    E.1.2Term Rheumatoid arthritis flare up
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess whether, in patients presenting with a disease flare after an initial response to infliximab, increasing either the infusion dose or infusion frequency results in a significant improvement in disease activity.
    E.2.2Secondary objectives of the trial
     To compare the impact on disease activity of increasing the infusion dose to increasing the infusion frequency.
     To compare whether the timing of the disease flare has an impact on the effect seen after the increase of dose or frequency.
     To compare the change in disease activity during the infusion interval.
     To asses the pharmaco-economic impact of each of the three study arm strategies.
     To assess the relationship between disease activity and markers for bone/cartilage turnover.
     To study and compare the pharmacokinetic changes during the treatment phases of each strategy and relate it to the disease activity.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    The subject must meet ALL of the criteria listed below for entry into the study:

    1) Subject must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.

    2) Subject aged 18 years or more, of either sex and any race, with RA according to ACR criteria (see appendix 4).

    3) Subject has RA according to ACR criteria (see appendix 3).

    4) Subject received the standard Remicade® dosing schedule as per the EU label: 3mg/kg (as per current clinical practice, rounding off [so as to empty the whole vial] will be allowed within specified limits (see Appendix 5) at approximately weeks 0, 2, 6, (and 14) in combination with methotrexate.

    5) Initial response documented by moderate or good DAS28 improvement (EULAR criteria) from week 0 to week 6 or 14 during the initial Remicade® induction period.

    6) Early disease flare as defined by the “inverse” EULAR criteria (see Appendix 4) and reflects

    (a) a DAS28 worsening of at least 0.6 between the time of initial response (i.e. at week 6 or 14 during the induction period; see above) and the next 8-weekly infusion (i.e. week 14 or 22 of the induction period, respectively) and
    (b) the resulting DAS28 value.

    7) Subjects must confirm that they are practicing adequate contraception:

    (a) Female subjects of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active during the study) must agree to use a medically accepted method of contraception or be surgically sterilized prior to screening, while receiving protocol-specified medication, and for 6 months after stopping the medication. Acceptable methods of contraception include condoms (male and female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, oral or injectable hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation).

    8) Female subjects of childbearing potential must have a negative pregnancy test at Screening.

    9) Subject must understand and be able to adhere to the dosing and visit schedules, and agree to record weekly disease activity VAS scores, and adverse events accurately and consistently in a weekly diary.

    10) Subjects must be elegible for anti-TNF treatment according to applicable local guidelines. For all patients chest X-ray and skin test results must be available at baseline.

    11) Subjects screening laboratory tests must meet the following criteria:
    • Hemoglobin 8.0 mg/dL or greater providing the low hemoglobin level is not due to diseases other than anemia of chronic inflammation.
    • WBC equal to or greater than 3,500 / mm3
    • Neutrophils equal to or greater than 1,500 / mm3
    • Platelets equal to or greater than 100,000 / mm3
    • Liver enzyme levels less than or equal to 3 times the upper limit of normal
    • Serum creatinine less than or equal to 1.5 mg/dL
    E.4Principal exclusion criteria
    The subject will be excluded from entry into the study if ANY of the criteria listed below are met.

    1) Subject is a female who is pregnant, intends to become pregnant during the study (or within 6 months after study completion), is nursing or not using adequate contraceptive measures.

    2) Subject has not observed the designated periods for any of the concomitant medications outlined in Section 7.2.

    3) Subject has used any investigational medical product within 30 days prior to enrollment.

    4) Subject has any clinically significant deviation from normal in the physical examination, Chest X-ray, or ECG that, in the investigator’s judgment, may interfere with the study evaluation or affect subject safety.

    5) Subject has rheumatic disease other than RA or has any systemic inflammatory condition with signs and symptoms that might confound the evaluations of safety and toxicity from the infliximab therapy, including, but not limited to, Lyme disease, systemic lupus erythematosus, infectious or reactive arthritis, Reiter’s syndrome, non-rheumatoid vasculitis, or parvovirus infection.

    6) Subject is in a situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study.

    7) Subject is participating in any other interventional study(ies).

    8) Subject is part of the staff or a family member of the staff personnel directly involved with this study.

    9) Subject has an allergic reaction to or has a sensitivity to the study drug or its excipients that requires corticosteroid pre-infusion medication.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint for the study is the change in RA disease activity and the comparison of its measurements between the 2 interventional study groups and the control group.

    RA disease improvement will be evaluated using the DAS28 scoring system, the EULAR and ACR criteria, quality of life measurement, pain assessment (VAS), and rescue medication consumption.

    The primary parameter for assessing RA disease improvement, however, is the DAS28-CRP score difference at the end of the study (study week 24) from the score measured at the beginning of the study (study week 0). A difference of 0.6 is considered to be clinically significant.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Information not present in EudraCT
    E.6.2Prophylaxis Information not present in EudraCT
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Information not present in EudraCT
    E.6.8Bioequivalence Information not present in EudraCT
    E.6.9Dose response Information not present in EudraCT
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic Information not present in EudraCT
    E.6.12Pharmacoeconomic Yes
    E.6.13Others Information not present in EudraCT
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Information not present in EudraCT
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Information not present in EudraCT
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) Information not present in EudraCT
    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 No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Evaluator Blind
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Approved dose of Remicade
    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.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA100
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    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
    The subject is considered to have completed the study EITHER upon the completion of the last protocol-specified visit or contact (eg, phone contact with the principal investigator or qualified designee), OR upon receiving the last dose of the study medication, if that occurs after the last protocol-specified visit or contact.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    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 state
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 315
    F.4.2.2In the whole clinical trial 315
    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 Decision2006-05-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2006-07-13
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2008-10-29
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