Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   37743   clinical trials with a EudraCT protocol, of which   6185   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2006-002787-26
    Sponsor's Protocol Code Number:DINORA4
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2008-02-12
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2006-002787-26
    A.3Full title of the trial
    A Double Blind, Randomized, Placebo Controlled, Multi-Center Trial of Anti-TNF╬▒ Chimeric Monoclonal Antibody (Infliximab, Remicade®) in Combination with Methotrexate in Patients with Very Early Inflammatory Arthritis
    A.3.2Name or abbreviated title of the trial where available
    DINORA
    A.4.1Sponsor's protocol code numberDINORA4
    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 SponsorVienna Medical University
    B.1.3.4CountryAustria
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    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 BV
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameRemicade
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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.IMP: 2
    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.2.1.1.1Trade name Methotrexat 'Lederle' Tabletten
    D.2.1.1.2Name of the Marketing Authorisation holderWyeth Pharma, ZUL: 1974.00.01/ 1974.01.01
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameMethotrexat 'Lederle' Tabletten
    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.3.11 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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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 typeFolic acid antagonist
    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 placeboPowder for solution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    D.8 Placebo: 2
    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
    Earliest clinically perceptible phase of arthritis. Classification criteria to delineate this group of patients are not available. Therefore eligibility will be based on three important criteria: 1) the duration of arthritis-symptoms, as evaluated by the patient; and 2) the presence of arthritis, as documented by the rheumatologist; and 3) the persistence of arthritis, as documented by a rheumatologist.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level PT
    E.1.2Classification code 10003246
    E.1.2Term 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 the study is to demonstrate that patients with very early arthritis have a higher probability of achieving a state of clinical remission at end of therapy if treated with infliximab plus MTX when compared to MTX monotherapy or supportive treatment only.
    E.2.2Secondary objectives of the trial
    In patients with very early arthritis, treatment with a combination of MTX and infliximab compared to MTX monotherapy or supportive therapy alone leads to less radiological progression at 30, 54 and 106 weeks.

    In patients with very early arthritis, treatment with a combination of infliximab plus MTX for 22-54 weeks leads to better clinical outcomes in RA composite scores as well as in individual RA core set variables and socio-economic variables at week 106 compared to MTX monotherapy or supportive therapy.

    Patients with very early arthritis have less frequent relapses until week 106 if treated with a combination of MTX and infliximab for 22 to 54 weeks compared to MTX monotherapy or supportive therapy alone.

    In patients with very early arthritis, prediction markers, with respect to diagnosis and response to therapy will be validated or developed. This study will allow to validate or characterize such models.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    All patients to be included into this trial must meet the following inclusion criteria:
    1) Men and women, ≥ 18 and ≤ 75 years of age, capable of understanding and signing an informed consent.
    2) The presence of arthritis:
    a) Must be established in a rheumatology center,
    b) Must be present in at least 2 joints of the 66 joint count, of which at least one joint must be an MCP-, or a PIP- (IP-) or a wrist- or a MTP-joint. Two MTP-joints will not suffice. Any kind of polyarthritis (≥ 6 joints of any kind) will be sufficient.
    c) Without any previous episodes of inflammatory joint disease
    3) Duration of symptoms :
    a) Must be assessed by the subject and should involve the inflamed joints described under 2.
    b) Must be 2 weeks at least, according to the algorithm in Table 1 (subjects will not receive study treatment before 12 weeks of symptom duration according to the algorithm in Table 1)
    c) Must be 16 weeks at most, as assessed by the subject, including the observation period of at least 2 weeks by the physician, according to the algorithm in Table 1.
    4) Confirmation of persistent arthritis:
    a) Duration must be 2 weeks at least, according to the algorithm in Table 1.
    b) Duration must be 12 weeks at most, according to the algorithm in Table 1.
    c) Must be documented by the same rheumatology center that established arthritis at the first visit
    d) Must involve at least one of the same joints as were involved at the first visit
    5) Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last medication.
    6) Are considered eligible according to the tuberculosis (TB) eligibility assessment, screening, and early detection of reactivation rules defined in Section 7.14: Tuberculosis Eligibility Assessment, Screening, and Early Detection of Reactivation
    7) Chest radiograph (which must not be older than three months at the visit 1/day 0 visit) must show no evidence of malignancy, infection, or fibrosis. The chest radiograph should also show no atypical scarring, cavitary lesions, or calcified granulomas, as evidence of past tuberculosis infections, without a documented history of adequate therapy.
    E.4Principal exclusion criteria
    Patients must not
    1) Have arthritis with a distinct diagnosis, made after a routine diagnostic work-up (examples are SLE, psoriatic arthritis, systemic sclerosis, gout, pseudogout, Lyme arthritis, reactive arthritis, Parvo viral arthritis)
    2) Be incapacitated, largely or wholly bedridden, or confined to a wheelchair, or have little or no ability for self care.
    3) Weigh more than 100 kg
    4) Use glucocorticoids > 10 mg/day prednisone or equivalent
    5) Have received Intramuscular or intra-articular injection of steroids in the previous month.
    6) Have Screening laboratory test results as follows:
    a) White blood cells (WBCs) < 3.0 x 109 cells/L
    b) Platelets < 100 X 109 cells/L
    c) Serum creatinine > 1.4 mg/dL
    d) Serum transaminase levels exceeding 2 times the upper limit of normal for the site laboratory
    7) Have had any previous treatment with monoclonal antibodies or antibody fragments.
    8) Have a history of receiving human/murine recombinant products or a known allergy to murine products. A known allergy to murine product is definitely an exclusion criterion.
    9) Have had prior treatment with MTX and/or other DMARDs (except hydroxychloroquine).
    10) Have documentation of seropositivity for human immunodeficiency virus (HIV).
    11) Have documentation of a positive test for hepatitis B surface antigen or hepatitis C-antibodies.
    12) Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results.
    13) Have a known history of serious infections (such as, but not limited to hepatitis, pneumonia, or pyelonephritis) in the previous 3 months.
    14) Have a known history of a demyelinating disease, such as multiple sclerosis
    15) Have or have had an opportunistic infection (eg, herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 12 months prior to screening.
    16) Have undergone any joint replacement surgery.
    17) Have a chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (eg. bronchiectasis), sinusitis, recurrent urinary tract infection, open, draining or infected skin wound or ulcer.
    18) Be considered ineligible according to the TB eligibility assessment, screening, and early detection of reactivation rules defined in Section on: Tuberculosis Eligibility Assessment, Screening, and Early Detection of Reactivation Rules
    19) Have a chest radiograph at screening that shows evidence of malignancy, infection, or any abnormalities suggestive of TB.
    20) Have a history of lymphoproliferative disease, including lymphoma or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic area), or splenomegaly.
    21) Currently have any known malignancy other than the condition being treated or have a history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence.
    22) Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
    23) Be unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.
    24) Use any investigational drug within 3 months prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
    25) Have presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening).
    26) Have a concomitant diagnosis or history of congestive heart failure (NYHA class III or IV).
    27) Be women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion
    E.5 End points
    E.5.1Primary end point(s)
    Comparison of presence of clinical remission between treatment with infliximab plus MTX versus MTX monotherapy and supportive treatment only at end of therapy, i.e. at at least 2 consecutive visits after month 3 during the first 54 weeks.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    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 Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    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) Yes
    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 No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    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 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 years4
    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 years4
    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 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.1.3Elderly (>=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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 200
    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)
    routine clinical care in a Rheumatology center
    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 Decision2008-05-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-10-22
    P. End of Trial
    P.End of Trial StatusOngoing
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA