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    The EU Clinical Trials Register currently displays   41200   clinical trials with a EudraCT protocol, of which   6743   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2004-005102-68
    Sponsor's Protocol Code Number:IM101-064
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-07-25
    Trial results Removed from public view
    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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2004-005102-68
    A.3Full title of the trial
    A Phase III, Multi-Center, Open Label Study to Evaluate the Efficacy, Tolerability and
    Safety of Abatacept (BMS-188667) in Subjects with Active Rheumatoid Arthritis on
    Background Non-Biologic DMARDs Who Have An Inadequate Response to Anti-TNF
    Therapy and Have Limited Therapeutic Options.

    Revised Protocol 3, incorporating Amendments 2, 3 and 8.
    + Protocol Amendments 1 & 5.
    + Protocol Amendment 11 - Site specific: All sites in Belgium (v1.0, dated 23-Sep-2008)
    A.4.1Sponsor's protocol code numberIM101-064
    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 SponsorBristol-Myers Squibb International Corporation
    B.1.3.4CountryBelgium
    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 Orencia
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Company
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 nameAbatacept
    D.3.2Product code BMS-188667
    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.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAbatacept
    D.3.9.1CAS number 332348-12-6
    D.3.9.2Current sponsor codeBMS-188667
    D.3.9.3Other descriptive nameCTLA4Ig
    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) 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 typeFusion protein
    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
    RHEUMATOID ARTHRITIS,NOS
    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
    Summarize incidence of adverse events/serious adverse events/discontinuations due to adverse events during 6 months of combined treatment with abatacept and 1 or more background non-biologic DMARDs approved for RA in subjects with active RA

    Long-Term Extension(Amdt 5)
    Assess long-term safety + tolerability of abatacept in subjects that completed the initial 6-month open-label treatment period. This amendment also allows continuous safety monitoring of abatacept

    E.2.2Secondary objectives of the trial
    Assess:
    -incidence of adverse events/serious adverse events/discontinuations between current and previous users
    -% subjects achieving clinically meaningful improvement in DAS28(reduction of at least 1.2 units) at Day 169(Month 6)
    -% subjects achieving Low Disease Activity(DAS28 =< 3.2) at Day 169
    -% subjects achieving remission(DAS28 < 2.6) at Day 169
    -disease activity as measured by Disease Activity Score-28(DAS28) over time
    -safety of chronic use of abatacept
    -discontinuation rate in subjects receiving abatacept
    -abatacept immunogenicity
    -changes in surrogate markers(hs-CRP, RF) in subjects receiving abatacept
    -improvement in physical functioning(HAQ) and in SF36 at Day 169
    -reduction in fatigue using Fatigue VAS at Day 169

    Long-Term Extension(Amdt 5)
    Assess:
    -abatacept efficacy+immunogenicity in combination with nonbiologic background DMARDs
    -maintenance of response in subjects who eliminate/reduce their dose of concomitant nonbiologic background DMARD therapy
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Subjects must meet the criteria of the American Rheumatism Association (1987) for
    the diagnosis of rheumatoid arthritis and the American College of Rheumatology
    (1991) functional classes I, II, or III. (see Appendices 1 and 2 of the protocol)
    2) Rheumatoid Arthritis for greater than 1 year from the time of the initial diagnosis of
    RA.
    3) Subjects with RA who are currently receiving or previously received an anti-TNF
    therapy at an approved labeled dose for at least 3 months, but had in the
    investigator’s opinion, an inadequate efficacy response to therapy. Subjects who
    discontinue or discontinued an anti-TNF therapy due to intolerance or safety will be
    considered as anti-TNF therapy failures at any time point after they have received
    their first dose of anti-TNF therapy.
    4) Men and women (not nursing and not pregnant) at least 18 years of age. Women of child bearing potential are eligible if they are practicing effective contraceptive measures.
    -Women of childbearing potential (WOCBP) must be using an adequate method of
    contraception to avoid pregnancy throughout the study and for up to 10 weeks after the last infusion of abatacept in such a manner that the risk of pregnancy is minimized.
    -WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity
    25 IU/L or equivalent units of HCG) within 48 hours prior to the start of study
    medication.
    5) Drug stabilization requirements:
    a) Subjects must be on one or more background non-biologic DMARD(s) at a stable
    dose for a 28 day period prior to treatment (Day 1).
    b) Oral corticosteroid treatment must be stabilized for at least 25 out of 28 days prior
    to treatment, (Day 1).
    6) Subjects must have a qualifying DAS28 >= 5.1.
    Subjects who have a DAS28 >= 4.8 but < 5.1 at screening, will be allowed to
    repeat the Tender and Swollen Joint Count and the subject’s assessment of disease
    activity (VAS) in order to reassess eligibility. These assessments may be repeated
    only once and must be completed within 2 weeks of the initial screening visit. The
    hs-CRP component may not be repeated.

    Long-Term Extension (Amendment 5)

    Subjects must continue to meet Inclusion/Exclusion criteria as outlined in Protocol
    IM101064 and/or all subsequent amendments, with the exception of the DAS 28 entry requirement or the requirement to be receiving a stable dose of a non-biologic DMARD.
    E.4Principal exclusion criteria
    1) Women who are pregnant or breastfeeding.
    2) Women with a positive pregnancy test on enrollment or prior to start of study drug
    administration.
    3) WOCBP using a prohibited contraceptive method (there are none).
    4) WOCBP who are unwilling or unable to use an acceptable method to avoid
    pregnancy for the entire study period and for up to 10 weeks after the last infusion of study medication.
    5) Subjects with active vasculitis of a major organ system (except for subcutaneous
    rheumatoid nodules).
    6) Current symptoms of severe, progressive, or uncontrolled renal, hepatic,
    hematological, gastrointestinal, pulmonary, cardiac, neurological, ophthalmologic or
    cerebral disease. Concomitant medical conditions that in the opinion of the
    Investigator might place the subject at unacceptable risk for participation in this
    study.
    7) Subjects with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing.
    8) Subjects who have a history of clinically significant drug or alcohol abuse. Subjects
    currently taking methotrexate or leflunomide who admit to consumption of more than
    an average of 1 alcoholic drink per day.
    9) Subjects with any serious bacterial infection (such as pneumonia, other renal infection and sinusitis), unless treated and resolved with antibiotics or chronic bacterial infection (such as pyelonephritis and chest infection with bronchiectasis) in the previous 3 months.
    10) Subjects with active tuberculosis requiring treatment within the previous 3 years.
    Subjects with a positive PPD at screening will not be eligible for the study unless they
    completed treatment for latent TB and have a negative chest x-ray at enrollment.
    11) Subjects with herpes zoster that resolved less than 2 months prior to enrollment.
    12) Subjects with evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at the time of potential enrollment, including subjects with evidence of Human Immunodeficiency Virus (HIV) infection.
    13) Significant toxicities associated with concomitant DMARD therapy or previous
    anti-TNF therapy that would preclude subjects from participating and completing the
    study.
    14) Subjects with repeated (at least 2) serious infections (such as pneumonia, other renal infections, sinusitis) requiring intravenous therapy while on anti-TNF therapy.
    15) Subjects with a history of severe allergic reaction(s) to Anti- TNF therapy.
    16) Subjects with any of the following laboratory values:
    • Hgb < 8.5 g/dL.
    • WBC < 3,000/mm3 (3 x 109/L).
    • Platelets < 100,000/mm3 (100 x 109/L).
    • Serum creatinine > 2 times upper limit of normal.
    • Serum ALT or AST > 2 times upper limit of normal.
    • Any other laboratory test results that, in the opinion of the investigator, might
    place the subject at unacceptable risk for participation in this study.
    17) Subjects previously treated with rituximab: B cell levels are less than lower limit of normal as measured by Fluorescent Activated Cell Sorting (FACS) analysis.
    18) Subjects who have at any time received treatment with BMS-188667, CTLA4Ig or
    abatacept.
    19) Subjects who have received treatment with any investigational drug within 28 days of the Day 1 dose.
    20) Subjects currently receiving treatment with mycophenolate mofetil (CellCept),
    cyclosporine and d-penicillamine or calcineurin inhibitors.
    21) Subjects who have received treatment with rituximab less than 12 months prior to screening.
    22) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
    E.5 End points
    E.5.1Primary end point(s)
    Physical examination findings, vital signs, laboratory test results and adverse events will be evaluated during the course of the study. Clinical response will be evaluated by the Disease Activity Score (DAS28) criteria. The DAS28 measures the current RA disease activity. The variables used to calculate the DAS28 include the number of swollen and tender joints using 28-joint counts, hs-CRP (measured in mg/L), the subject global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm. Other responses (e.g.HAQ) outcome measures (e.g., SF-36), physician’s global assessment of disease activity will also be evaluated.
    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 No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    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 Yes
    E.8.5.1Number of sites anticipated in the EEA33
    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 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
    Last patient last visit.
    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 months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    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 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 state38
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 190
    F.4.2.2In the whole clinical trial 750
    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)
    A long term extension phase will be offered to subjects that complete the initial 6 month study phase and are still eligible to continue into the long term extension. The long-term extension will continue until abatacept is launched in the local country, or until the clinical development has been discontinued. The extension phase in Belgium will end in April 2009 or whenever the product is commercially available (is reimbursed in Belgium) - whichever is earlier.
    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 Decision2005-06-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-11-15
    P. End of Trial
    P.End of Trial StatusCompleted
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