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    Summary
    EudraCT Number:2006-004673-98
    Sponsor's Protocol Code Number:ML 20538
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2006-09-08
    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 ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2006-004673-98
    A.3Full title of the trial
    Efficacy of Rituximab treatment in patients with rheumatoid arthritis having inadequate response to TNF blocker
    A.4.1Sponsor's protocol code numberML 20538
    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 SponsorRoche (Hungary) Ltd.
    B.1.3.4CountryHungary
    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 MabThera 500 mg concentrate for solution for infusion
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Ltd.
    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 Concentrate 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 typemouse/human monoclonal chimeric 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
    To investigate the efficacy of treatment with Rituximab (MabThera®) in patients with active RA whose current treatment with one or more TNF-blocker (Etanercept - Enbrel®, Infliximab – Remicade® or Adalimumab - Humira®) alone or in combination with MTX is insufficient measured by DAS28 activity index.
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To investigate the efficacy of treatment with Rituximab (MabThera®) in patients with active RA whose current treatment with one or more TNF-blocker (Etanercept - Enbrel®, Infliximab – Remicade® or Adalimumab - Humira®) alone or in combination with MTX is insufficient measured by DAS28 activity index.
    E.2.2Secondary objectives of the trial
    • The ACR response criteria (20%, 50%, 70%)
    • HAQ
    • Laboratory assessments (ESR, CRP, CBC and routine blood chemistry albumine, creatinine, blood urea nitrogen, serum electrolites, ALAT, ASAT and urine analysis will be performed
    • Autoantibodies assessments (Anti-cyclic citrullinated peptide (Anti-CCP), Rheumatoid Factor
    • Serum VEGF level assessment
    • Safety assessments, adverse events
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Women or men 18 years of age or older
    • Diagnosis of RA according to the revised 1987 criteria of the ARA for at least 3 months prior to first administration of study medication
    • Inadequate response or intolerance to one or more anti-TNF-therapies alone or in combination with MTX
    • Wash out period for anti-TNF therapies: 4 weeks for etanercept, 8 weeks for infliximab and for adalimumab
    • Active disease at the time of screening as defined by:
    - ≥ 6 swollen on a 66/68 joint count
    - ≥ 6 tender joints on a 66/68 joint count
    • And one out of the following 3 categories:
    - ESR ≥ 28 mm/ h
    - CRP ≥ 1.5 mg/ dl
    - Morning stiffness ≥ 45 min
    • And one out of the following 2 categories:
    - Anti-cyclic citrullinated peptide (Anti-CCP) antibody-positive
    - Rheumatoid factor (RF)-positive at screening
    • If using NSAIDs or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent.
    • If using oral corticosteroids, must be on a stable dose equivalent to ≤ 10 mg of prednisone/day for at least 2 weeks prior to first administration of study agent. If currently not using corticosteroids, the subject must not have received oral corticosteroids for at least 2 weeks prior to first administration of study medication.
    • Women of childbearing potential or men capable of fathering children must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization) during the study and for 6 months after receiving the last administration of study agent.
    • Female subjects of childbearing potential must test negative for pregnancy. A pregnancy test will be performed at the beginning and at the end of the study.
    • The screening laboratory test must meet the following criteria:
    - Hemoglobin ≥ 8.5 g/ dl providing the low hemoglobin level is not due to other diseases than anemia of chronic inflammation.
    - WBC ≥ 3500 / μl
    - Neutrophils ≥ 1500 / μl
    - Platelets ≥ 100 000 / μl
    - Serum transaminase ≤ 2 times the upper limit of normal
    - Serum creatinine ≤ 1.7 mg/ dl
    • The patient must be able to adhere the study visit schedule and other protocol requirements and must have given informed consent prior to any screening procedures.
    • Patients who, in the opinion of the investigator, are able to understand and complete the questionnaires, are willing and able to comply with the protocol requirements;
    • Patients who have signed the informed consent
    E.4Principal exclusion criteria
    • Pregnant women, nursing mothers or a planned pregnancy within six months after last scheduled treatment.
    • Patients with other inflammatory diseases that might interfere with the evaluation of the RA.
    • Severe heart failure ( NYHA class IV) or severe, uncontrolled cardiac disease
    • Patients with fibromyalgia syndrome.
    • Use of IM, IV, IA cortocisteroids within 4 weeks prior to screening.
    • Treatment with any investigational drug within 3 months prior to screening.
    • A history of known allergy to murine proteins, e.g. allergy to Infliximab.
    • History of infected joint prothesis within the previous 5 years.
    • Chronic infections.
    • Known active bacterial, viral, fungal, mycobacterial or other infection (including tuberculosis, or atypical mycobacterial disease, but excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening.
    • History of recurrent significant infection or history of recurrent bacterial infections.
    • Primary or secondary immunodeficiency (history of, or currently active).
    • Current signs or symptoms of other severe uncontrolled disease which in the investigators opinion would put the patient at an unacceptable risk.
    • History of lymphoproliferative disease, any current malignancies or history of malignancy within 5 years other than successfully treated basal cell carcinoma or squamous cell carcinoma of the skin.
    • History of drug abuse.
    E.5 End points
    E.5.1Primary end point(s)
    DAS 28 Assessments
    measure will be the frequency of reaching low disease activity or remission as measured by the DAS28<3,2 at 24 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 Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    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 No
    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
    March 2008
    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 months6
    E.8.9.1In the Member State concerned days
    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 20
    F.4.2.2In the whole clinical trial 20
    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)
    After the subject has ended his/her participation in the trial he/she will be treated as routin clinical practice decided by his/her own physician
    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 Decision2006-10-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2006-10-04
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2009-03-10
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