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   37221   clinical trials with a EudraCT protocol, of which   6123   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:2016-002344-16
    Sponsor's Protocol Code Number:RR16/209
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-11-29
    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 ConcernedUK - MHRA
    A.2EudraCT number2016-002344-16
    A.3Full title of the trial
    Targeted treatment early with etanercept (biosimilar) plus methotrexate or methotrexate with T2T care for DMARD-naïve early RA patients. A prospective, longitudinal cohort study with an embedded pilot randomised controlled trial to assess treatment rationalisation based on naïve CD4+ T-cell stratification.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Targeted treatment early with etanercept and methotrexate or methotrexate with treat to target (standard) care for treatment-naive early rheumatoid arthritis patients, based on baseline naive T-cell frequency.
    A.3.2Name or abbreviated title of the trial where available
    TEEMS
    A.4.1Sponsor's protocol code numberRR16/209
    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 of Leeds
    B.1.3.4CountryUnited Kingdom
    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 Benepali
    D.2.1.1.2Name of the Marketing Authorisation holderSamsung Bioepis
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameBenepali
    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 CodeAS1
    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 Yes
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Rheumatoid Arthritis
    E.1.1.1Medical condition in easily understood language
    Rheumatoid Arthritis - The most common form of inflammatory arthritis. It is a condition where your body’s immune system causes joints to become swollen and damaged.
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    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
    Overall Aim: To determine whether a patient's baseline naive T-cell frequency can guide treatment decisions for treatment-naive early RA patients. Specifically, can we rationalise the use of MTX and offer more targeted treatment for patients with a poor prognosis based on their naive T-cells?

    Primary Objective:

    To determine whether the proportion of patients achieving clinical remission after first-line treatment with methotrexate and standard treat to target care differs according to naive CD4+ T-cell frequency (normal/abnormal) at baseline.


    E.2.2Secondary objectives of the trial
    1. To determine the proportion of patients that achieve clinical remission for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving etanercept + methotrexate compared to methotrexate with T2T care.

    2. To determine whether the proportion of patients that achieve ultrasound remission (absence of inflammation on ultrasound) with first-line treatment with MTX and T2T care differs according to naïve T-cell frequency (normal/abnormal) at baseline.

    3. To determine the proportion of patients that achieve ultrasound remission for patients with abnormal baseline naïve T-cell frequencies receiving etanercept + MTX compared to MTX with T2T care.

    4. To determine the proportion of patients who normalize their T-cell frequency for patients with abnormal baseline naïve T-cells receiving MTX with T2T care or etanercept + MTX.

    5. To determine whether patient reported outcomes differ between patients with normal or abnormal baseline naive T-cells.

    6. To determine whether the prop
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject has a diagnosis of RA as defined by the new ACR/EULAR 2010 classification criteria
    2. Newly diagnosed (within 12 weeks)
    3. Active disease at screening (DAS28ESR ≥3.2)
    4. Anti-citrillunated peptide protein antibody positive (ACPA)
    5. Male & female subjects ≥18 years old.
    6. DMARD-naïve
    7. No use of intra-muscular/Intra-articular or oral corticosteroids 4 weeks prior to screening.
    8. All male and female subjects biologically capable of having children must agree to use a reliable method of contraception for the duration of the study and 24 weeks after the end of the study period. Acceptable methods of contraception are surgical sterilisation, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives.
    9. Patients must have the capacity and be willing to provide written informed consent and comply with the requirements of the protocol.
    10. Subjects deemed to be in good health with respect to clinical examination and screening blood tests, including full blood count (FBC), urea and electrolytes (U&E), and liver functions tests (LFT)- See below exclusion criteria
    E.4Principal exclusion criteria
    1. Use of any additional investigational medications or products within 4 weeks of screening.
    2. Use of intramuscular, intra-articular or oral corticosteroids within 4 weeks prior to screening.
    3. Pregnant/lactating women or planning pregnancy within 24 weeks of last protocol treatment
    4. Planned surgery within the study period (requiring omission of study medication > 28 days).
    5. The presence of other comorbidities, which the physician deems as significant to interfere with evaluation (musculoskeletal condition such as osteoarthritis & fibromyalgia).
    6. Diagnosis of another inflammatory arthritis or conective tissue disease e.g. psoriatic arthritis or Ankylosing spondylitis, primary Sjogren’s syndrome, systemic sclerosis, systemic lupus erythematosus, polymyositis.
    7. Patients with any ongoing or active infection or any major episode of severe infection requiring hospitalization or treatment with IV antibiotics within the preceding 4 weeks of screening and/or orally administered antibiotics in the preceding 2 weeks of screening.
    8. Any contraindication to conventional DMARD’s and anti-TNF therapy
    9. In receipt of a live vaccination within 4 weeks prior to screening
    10.Patients with abnormal liver function at the time of screening or abnormal blood tests as shown by: 

    o Aminotransferase (AST)/alanine aminotransferase (ALT) >3x upper limit of normal (ULN), OR Bilirubin >51µmol/L 

    o Serum Creatinine >175 mmol/L, eGFR below 30ml/L/min/1.73m2
    o Neutrophils <2000 x 10*6/L 

    o Platelets <125 x 109/L
    
o Haemoglobin <90 g/L for males and <85 g/L for females 


    E.5 End points
    E.5.1Primary end point(s)
    The difference in the proportions of patients in clinical remission (DAS28 ≤2.6) at 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies.
    E.5.1.1Timepoint(s) of evaluation of this end point
    24 weeks
    E.5.2Secondary end point(s)
    • The difference in the proportions of patients in clinical remission (DAS28 ≤2.6) after 12 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies

    • The difference in the proportions of patients in clinical remission (DAS28 ≤2.6) at 12 weeks and 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C)

    • The differences in the medians of patient-reported outcome measures (EMS, VAS scales, HAQ-DI) after 12 weeks & 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies

    • The differences in the medians of patient-reported outcome measures (EMS, VAS scales, HAQ-DI) after 12 weeks & 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care(Arm B) vs. etanercept + methotrexate (Arm C)

    • The difference in the proportions of patients in imaging remission (PD=0) after 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) or abnormal (Arm B) naïve CD4+T-cell frequencies

    • The difference in the proportions of patients in imaging remission (PD = 0) 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C)

    • The difference in the proportion of patients with normal naïve CD4+ T-cells at 24 weeks (24 weeks)for patients with abnormal baseline naïve CD4+ T-cells receiving methotrexatewith T2T care (Arm B) vs. etanercept +
    methotrexate (Arm C)

    • The difference in the proportions of patients achieving sustained clinical remission (DAS28ESR ≤2.6 at both 12 and 24 weeks) (Arm A vs. Arm B and Arm B vs. Arm C)

    • The difference in the average (median) cumulative amount of intramuscular corticosteroid use at 24 weeks between study arms (Arm A vs. Arm B and Arm B vs. Arm C). This will include any administered at the 24 week visit.
    E.5.2.1Timepoint(s) of evaluation of this end point
    As outlined above
    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 No
    E.6.5Efficacy No
    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
    Remission Induction
    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 Yes
    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 No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Information not present in EudraCT
    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
    When all patients have completed 24 weeks of follow-up of the trial, any safety data are resolved and procedures are signed off and all analyses of laboratory samples are complete.
    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 days1
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 0
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 0
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state106
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 106
    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)
    When the study has finished, all patients will continue to be followed up and treated as per standard NHS/T2T care in either an established inflammatory arthritis or biologics clinic (based on disease activity at 24 weeks). The benepali group will discontinue this drug.This may be re-commenced in the biologic clinic for patients who are eligible based on their disease activity status.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation CRN: Yorkshire and Humber, Sheffield Teaching Hospitals NHS Foundations Trust
    G.4.3.4Network Country United Kingdom
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-01-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-06-28
    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