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    The EU Clinical Trials Register currently displays   43207   clinical trials with a EudraCT protocol, of which   7151   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2017-004054-41
    Sponsor's Protocol Code Number:KCE-16002
    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:2018-03-15
    Trial 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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2017-004054-41
    A.3Full title of the trial
    CareRA2020: Effectiveness of a combination of Methotrexate and a step down glucocorticoid regimen (COBRA-Slim) for remission induction in patients with early Rheumatoid Arthritis (RA), with or without fast access to 24 weeks of Tumor Necrosis Factor (TNF) blockade in insufficient responders, a randomized, multicenter, pragmatic trial.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    COBRA-Slim with or without fast access to TNF blockade for remission induction in early RA
    A.3.2Name or abbreviated title of the trial where available
    CareRA2020
    A.4.1Sponsor's protocol code numberKCE-16002
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUniversity Hospitals Leuven
    B.1.3.4CountryBelgium
    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 supportBelgian Health Care Knowledge Center (KCE)
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Hospitals Leuven
    B.5.2Functional name of contact pointPatrick Verschueren
    B.5.3 Address:
    B.5.3.1Street AddressHerestraat 49
    B.5.3.2Town/ cityLeuven
    B.5.3.3Post codeB-3000
    B.5.3.4CountryBelgium
    B.5.4Telephone number+321634 25 41
    B.5.6E-mailpatrick.verschueren@uzleuven.be
    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.2.1.2Country which granted the Marketing AuthorisationBelgium
    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 nameetanercept
    D.3.4Pharmaceutical form Solution for injection in pre-filled pen
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNETANERCEPT
    D.3.9.1CAS number 185243-69-0
    D.3.9.4EV Substance CodeSUB01984MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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 No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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.2.1.2Country which granted the Marketing AuthorisationBelgium
    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 Coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLEFLUNOMIDE
    D.3.9.1CAS number 75706-12-6
    D.3.9.4EV Substance CodeSUB08424MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number10 to 20
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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 No
    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
    early active Rheumatoid Arthritis, previously untreated with DMARDs
    E.1.1.1Medical condition in easily understood language
    early active Rheumatoid Arthritis, previously untreated with DMARDs
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10039073
    E.1.2Term Rheumatoid arthritis
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    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 is to compare in an early RA population with insufficient response (not achieving DAS28CRP≤3.2 within 32 weeks) to COBRA-Slim remission induction, the long term effectiveness of accelerated access to a six-month course of anti-TNF therapy (etanercept) within a time window from w8 up to w32, versus further treatment adaptation according to the standard COBRA-Slim strategy.
    E.2.2Secondary objectives of the trial
    Main secondary objective
    To investigate in insufficient responders to the COBRA-Slim regimen if accelerated access to a six-month course of anti-TNF therapy (etanercept), is leading to improved remission rates when compared to conventional treatment adaptation according to the COBRA-Slim strategy, 28 weeks after randomization into one of two treatment arms.

    Other secondary objectives:
    1. To further determine the clinical efficacy of accelerated access to etanercept versus the standard COBRA-Slim strategy in terms of remission rates and functionality scales.
    2. To compare radiographic progression between all treatment schemes.
    3. To evaluate the side effects of the given treatments as evaluated according to the regulatory guidelines for marketed products.
    4. To evaluate the primary outcome using the DAS28ESR instead of the DAS28CRP.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Age 18 years and older
    - Diagnosis of RA as defined by the ACR/EULAR2010 criteria for early RA
    - Early RA defined by a diagnosis made ≤ 1 year ago.
    - Use a reliable method of contraception for women of childbearing potential
    - Able and willing to give written informed consent and to participate in the study
    - Understanding and able to write Dutch or French
    E.4Principal exclusion criteria
    - Previous treatment with:
    o MTX or leflunomide
    o cyclophosphamide, azathioprine or cyclosporine
    o sulphasalazine (SSZ) for more than 3 weeks
    o hydroxychloroquine for more than 6 weeks
    o oral GC for more than 4 weeks within 4 months before screening
    o oral GC at a daily dosage of more than 10 mg prednisone equivalent within 4 weeks before baseline
    o oral GC at a daily dosage equal to or less than 10 mg prednisone equivalent within 2 weeks before baseline
    o intra-articular GC within 4 weeks before BL
    o an investigational drug for the treatment/prevention of RA
    - History of chronic heart failure
    - History of severe infections or chronic infection
    - History of malignant neoplasm within 5 years
    - Contra indications for GC
    - Contra indications for TNF blocking agents
    - Contra indications for Methotrexate
    - Psoriatic Arthritis
    - Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases or immune deficiency which in the opinion of the investigator places the patient at an unacceptable risk for participation in the study
    - Pregnancy, breastfeeding or no use of a reliable method of contraception for woman of childbearing potential
    - Alcohol or drug abuse
    - Active TB
    - Latent TB unless adequate prophylactic treatment is given
    - No access to the Belgian Health Insurance system
    E.5 End points
    E.5.1Primary end point(s)
    Area under the curve of DAS28-CRP over 104 weeks (long term effectiveness) in insufficient responders randomized to either COBRA-Slim Bio-Induction or Standard COBRA-Slim Induction.
    E.5.1.1Timepoint(s) of evaluation of this end point
    at week 104
    E.5.2Secondary end point(s)
    Main secondary outcome measure
    Proportion of insufficient responders achieving remission (DAS28CRP<2.6) 28 weeks after randomization (short term efficacy) to either COBRA-Slim Bio-Induction or Standard COBRA-Slim Induction.
    Other secondary outcome measures
    The following analyses will be performed in the randomized early insufficient responder population (w8-w32) with or without accelerated access to a six-month course of etanercept. The same analyses will also be performed including the randomized groups of insufficient responders, each completed with an early responder control population.

    1. Clinical efficacy:
    o Remission (DAS28CRP<2.6) at w104.
    o EULAR response at 28 weeks after randomization and at w104
    o HAQ response at 28 weeks after randomization and at w104
    2. Radiographic progression: X-ray evolution at w52 and w104 compared to BL as reviewed and evaluated by the central team.
    3. Side effects: (S)ARs from BL until w104
    4. To evaluate the primary outcome using the DAS28ESR instead of the DAS28CRP.
    E.5.2.1Timepoint(s) of evaluation of this end point
    at 28 weeks after randomisation;
    at week 52;
    at week 64;
    at week104
    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 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 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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    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
    prospective study to evaluate the role of a biological in a remission induction scheme
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned20
    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 No
    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
    LVLS
    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 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.1.2.1Number of subjects for this age range: 385
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 55
    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 state440
    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)
    as this is a pragmatic trial, patients will continue on standard of care treatment for rheumatoid arthritis patients
    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 Decision2018-05-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-05-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-07-01
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