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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.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
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    Summary
    EudraCT Number:2005-000784-26
    Sponsor's Protocol Code Number:IM101-023
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-09-28
    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 ConcernedGermany - PEI
    A.2EudraCT number2005-000784-26
    A.3Full title of the trial
    A Phase IIIB, Multi-Center, Randomized, Double Blind, Study to Evaluate Remission and Joint Damage Progression in Methotrexate Naive Early Erosive RA Subjects Treated with Abatacept Plus Methotrexate Compared with Methotrexate.
    Revised Protocol 04, incorporating Protocol Amendments 05, 06, 08, 09 (V1.0 dated 18-Nov-2008) and Administrative Letter 02. Pharmacogenetics Amendment 1 dated 16-May-2005. Protocol Amendments 3 & 4 - Site Specific - dated 28-Dec-2005. And Protocol Amendment 07 - Site Specific (v2.0, date 27-Jul-2007).
    A.4.1Sponsor's protocol code numberIM101-023
    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 injection
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    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
    The co-primary objectives for this study will compare the clinical efficacy of abatacept
    used in combination with methotrexate versus methotrexate alone on the following:
    1) The proportion of subjects who achieve remission in 12 months of treatment
    (Day 365), as defined by a DAS 28 score less than 2.6 and
    2) Joint damage progression measured by radiographic evaluation using the
    Genant-Modified Sharp total score at 12 months of treatment (Day 365).

    E.2.2Secondary objectives of the trial
    1) Compare proportion of subjects with an ACR50 response at month 12 (Day 365).
    2) Compare proportion of subjects achieving major clinical response defined by
    6 months of consecutive ACR 70 response at month 12 (Day 365).
    3) Compare disease activity as measured by DAS 28 score at month 12 (Day 365).
    4) Compare improvement in physical function using the HAQ disability index at
    month 12 (Day 365) and assess improvement in physical function at month 24
    (Day 729).
    5) Compare inhibition of joint damage progression measured by radiographic
    evaluation using the Genant-modified Sharp erosion, and joint space narrowing at
    month 12 (Day 365).
    6) Assess inhibition of joint damage progression measured by radiographic
    evaluation using the Genant-modified Sharp erosion, joint space narrowing and total
    score at month 24 (Day 729).
    7) Determine safety and tolerability of abatacept in this subject population, including evaluation of immunogenicity of abatacept.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    * MRI Exploratory Research Sub-Study Amendment 3 - Site specific, Version 3.0, dated 28-Dec-2005.

    The primary objective of this amendment is to assess the change in structural joint damage measured by Magnetic Resonance Images from Day 1 to month 12 between abatacept/methotrexate versus methotrexate alone.

    * dose reduction/long term extension sub-study Amendment 07 - Site Specific, version 2.0, dated 27-Jul-2007.

    The primary objective of this sub-study is to assess the time to disease relapse for the abatacept 10 mg/kg and 5 mg/kg doses in subjects with early RA in remission (DAS 28 ESR < 2.6) who have received treatment with abatacept 10 mg/kg for at least one year. A relapse will be defined as follows:
    • Additional DMARD therapy given
    • Two or more course of high dose steroids given
    • Return to abatacept 10 mg/kg (rescue medication given)
    • DAS28 CRP score ≥ 3.2 at 2 consecutive visits


    * RNA Exploratory Research Sub-Study Amendment 4 - Site specific, version 2.0, dated 28-Dec-2005.

    The primary objective of this amendment is to analyze RNA expression patterns as a potential biomarker in RA and to confirm the presence of distinct RNA expression patterns in RA subjects.
    E.3Principal inclusion criteria
    1) Subject is willing to participate in the study and has signed the informed consent.
    2) Males or females (not nursing and not pregnant) ≥ 18 years of age. Males and
    women of child-bearing potential are eligible if they are practicing effective
    contraceptive measures.
    3) Subjects must meet the criteria of the American Rheumatism Association (1987) for
    the diagnosis of rheumatoid arthritis.
    4) Subjects must have a diagnosis of RA less than or equal to 2 years.
    5) Subjects must have high disease activity as defined by a tender joint count of at least 12, swollen joint count of at least 10, and a CRP of ≥ .45 mg/dL or ≥ 4.5 mg/L.
    6) Subjects that are RF or anti-CCP positive.
    7) Subjects must have evidence of erosion of the hands, wrists or feet on the screening radiograph. (To be read centrally)
    8) Subjects must be methotrexate naive or their prior exposure must have been ≤10mg a week for not more than 3 weeks and no dose for 3 months prior to signing the informed consent.
    9) Men and women (not nursing and not pregnant) ≥ 18 years of age. Men and Women of childbearing potential are eligible if they are practicing effective contraceptive measures.
    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.
    Male subjects must be using an adequate method of contraception throughout the study including up to 10 weeks after the last infusion of abatacept so that the risk of pregnancy to their partner is minimized.
    E.4Principal exclusion criteria
    1) 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 abatacept.
    2) Subjects who are impaired, incapacitated, or incapable of completing study related
    assessments.
    3) Subjects who meet diagnostic criteria for any other rheumatic disease (e.g., lupus
    erythematous).
    4) Subjects who have previously received treatment with an approved or investigational biologic RA therapy (infliximab, etanercept, anakinra, adalimumab).
    5) Subjects with active vasculitis of a major organ system with the exception of
    rheumatoid nodules.
    6) Subjects with current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, or other medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.
    7) Female subjects, who have not had age and/or risk factor appropriate breast cancer screening or who have had a breast cancer screening study that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations (Please refer to Section 7.3.2).
    8) 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.
    9) Subjects who have clinically significant drug or alcohol abuse.
    10) Subjects with any serious acute bacterial infection (such as pneumonia or
    pyelonephritis) unless treated and completely resolved with antibiotics.
    11) Subjects with severe chronic or recurrent bacterial infections (such as recurrent
    pneumonia, chronic bronchiectasis).
    12) The following subjects are excluded from this study:
    - Subjects with current clinical or laboratory evidence of active or latent
    tuberculosis (TB).
    - Subjects with a history of active TB that was treated within the last 3 years.
    - Subjects with a history of active TB greater than 3 years ago unless there is
    documentation that the prior anti-TB treatment was appropriate in duration and
    type.
    13) Subjects with herpes zoster that resolved less than 2 months prior to enrollment.
    14) 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.
    15) Subjects with Hepatitis B surface antigen.
    16) Subjects with Hepatitis C antibody-positive subjects who are also RIBA-positive or PCR-positive.
    17) 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.
    18) Subjects with a history of intolerance to methotrexate.
    19) Subjects who have at any time received treatment with CTLA4Ig, BMS-188667
    (abatacept).
    20) Subjects who have received treatment with any investigational drug within 28 days (or less than 5 terminal half-lives of elimination) of the Day 1 dose.
    21) Subjects currently receiving treatment with leflunomide, mycophenolate mofetil
    (CellCept), cyclosporine, and tacrolimus, D-Penicillamine, Cytoxan, or immunoadsorption columns (such as Prosorba columns).
    22) No approved or investigational biologics
    23) 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)
    Efficacy:
    Co-primary efficacy analysis include, in the order of sequential testing, comparisons
    between abatacept in combination with methotrexate and a placebo control of
    methotrexate alone in remission rate (EULAR defined DAS 28 remission) by 12 months (Day 365) and total Sharp scores using the Genant-modified Sharp method at 12 months (Day 365).
    The co-primary efficacy analysis will be performed with the intent-to-treat (ITT) analysis population including all subjects randomized and treated. All subjects who prematurely discontinue the trial after receiving study medication will have missing data imputed as a DAS 28 remission non-responder at all scheduled protocol visits subsequent to the point of discontinuation. Missing annual radiographic data will be imputed with linear extrapolation for discontinued subjects having baseline radiographs and at least one of either Day 169 radiographs or discontinuation radiographs. Subjects with missing baseline radiographic data will be excluded from the primary radiographic analyses.
    The DAS 28 is a continuous variable which is a composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, CRP and subject assessment of disease activity measure on a visual analog scale.

    Safety:
    The evaluation of drug safety is based on clinical AEs, vital signs and laboratory
    abnormalities reported during the study. All safety presentations will include subjects
    who received at least one dose of study medication and will group subjects by treatment received.
    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 Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity
    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) 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA43
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    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 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 state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 383
    F.4.2.2In the whole clinical trial 750
    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 Decision2005-11-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-11-23
    P. End of Trial
    P.End of Trial StatusCompleted
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