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   41189   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) .
     
    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:2014-003255-54
    Sponsor's Protocol Code Number:RGB-03-104
    National Competent Authority:Czechia - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-10-24
    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 ConcernedCzechia - SUKL
    A.2EudraCT number2014-003255-54
    A.3Full title of the trial
    A Double-blind, Randomised, Comparative Pharmacokinetic, Pharmacodynamic, Efficacy and Safety Evaluation of RGB-03 and MabThera® Combined with Methotrexate in Rheumatoid Arthritis Patients
    Dvojitě zaslepené, randomizované, srovnávací klinické hodnocení farmakokinetiky, farmakodynamiky, účinnosti a bezpečnosti přípravku RGB-03 a MabThera® v kombinaci s metotrexátem u pacientů s revmatoidní artritidou
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study evaluating the effects of RGB-03 and MabThera combined with Methotrexate in patients with Rheumatoid Arthritis
    A.4.1Sponsor's protocol code numberRGB-03-104
    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 SponsorGedeon Richter Plc
    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 supportGedeon Richter Plc
    B.4.2CountryHungary
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGedeon Richter Plc
    B.5.2Functional name of contact pointGedeon Richter Plc
    B.5.3 Address:
    B.5.3.1Street AddressGyömrői út 19-21
    B.5.3.2Town/ cityBudapest
    B.5.3.3Post codeH-1103
    B.5.3.4CountryHungary
    B.5.6E-mailRA.ctaRichter@richter.hu
    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 No
    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 nameRGB-03
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    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 INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.2Current sponsor codeRGB-03
    D.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 Yes
    D.3.11.13.1Other medicinal product typeBiosimilar
    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.2.1.1.1Trade name MabThera
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    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 No
    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 INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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.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
    E.1.1.1Medical condition in easily understood language
    Chronic inflammatory disease of the joints
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    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
    To evaluate the pharmacokinetics of RGB-03 and its reference product MabThera® in a comparative manner in rheumatoid arthritis patients to establish biosimilarity.
    E.2.2Secondary objectives of the trial
    To evaluate the efficacy, pharmacodynamics and safety characteristics of RGB-03 and its reference product MabThera® in a comparative manner rheumatoid arthritis patients to establish biosimilarity.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    To be eligible for the study entry patients MUST satisfy all of the following criteria at Screening:
    1. Age: 18-75 years, inclusive;
    2. Gender: male or female;
    3. Rheumatoid arthritis (RA) as defined by the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria;
    4. Active disease, defined as
    a. at least 6 swollen joints (66 joints assessed), AND
    b. at least 6 tender joints (68 joints assessed), AND
    c. elevated acute phase protein (serum C-reactive protein [CRP] ≥10 mg/L OR an erythrocyte sedimentation rate [ESR] ≥28 mm/hour), AND
    d. Disease activity score [DAS]28-ESR >3.2;
    5. Inadequate response to adequate treatment with at least one anti-tumour necrosis factor (TNF) drug (infliximab [≥3 mg/kg, ≥4 infusions {i.e. ≥14 weeks}], adalimumab [40 mg every other week ≥3 months], etanercept [25 mg twice weekly or 50 mg weekly ≥3 months], certolizumab pegol [400 mg every 2 weeks {given 3 times}, then 200 mg every 2 weeks, total administration ≥3 months], or golimumab [50 mg every 4 weeks ≥4 months]), and discontinued the biological treatment due to lack of efficacy or due to being intolerant to at least one administration of these agents;
    6. Treatment with oral or parenteral methotrexate (MTX) (10 to 25 mg/week) for 12 weeks prior to Screening, at a stable dose at least in the last 4 weeks;
    7. Adequate screening with documented negative results for latent tuberculosis using state-of-the art interferon gamma release assay test (QuantiFERON® TB Gold) and other assessments if deemed necessary based on the local requirements and/or according to the Investigator’s discretion (e.g. chest radiograph);
    8. Female patients of childbearing potential must have a negative serum pregnancy test (serum beta-human chorionic gonadotropin) at Screening unless they are surgically sterile (documentation should be available) or have been postmenopausal for ≥1 year (12 consecutive months without period);
    9. Women of childbearing potential must use medically acceptable means of birth control and agree to continue its use and perform regular pregnancy tests during the study and up to 12 months following the last IMP infusion;
    - be abstinent (true abstinence in line with the preferred and usual lifestyle of the subject) or be using one of the following acceptable birth control methods:
    a. implants, injectables, combined oral contraceptives, and intrauterine devices;
    b. combination of 2 barrier methods (condom, diaphragm) with spermicide;
    c. sole male partner of the subject has been sterilised (documentation should be available);
    10. Male patients should be surgically sterile (documentation should be available), be abstinent (true abstinence in line with the preferred and usual lifestyle of the subject) or agree together with their partner to use one of the following medically acceptable means of birth control during the study and up to 12 months following the last IMP infusion:
    a. implants, injectables, combined oral contraceptives, and intrauterine devices;
    b. combination of 2 barrier methods (condom, diaphragm) with spermicide;
    c. sole female partner of the subject is surgically sterile (documentation should be available) or has been postmenopausal for ≥1 year (12 consecutive months without period);
    11. Patients must be able to understand and provide written informed consent to participate in the study and understand that they are free to withdraw from the study at any time.
    E.4Principal exclusion criteria
    If any of the following apply at Screening, the patient MUST NOT enter the study:
    1. Rheumatoid arthritis patients with functional status class IV classified according to the revised ACR criteria (see Appendix 17.3);
    2. Patients with significant systemic manifestations of RA (e.g. vasculitis, pulmonary fibrosis, or Felty's syndrome);
    3. Patients seropositive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) on screening assay;
    4. Previous treatment with rituximab;
    5. Concurrent treatment with any synthetic DMARDs other than MTX within 28 days prior to Screening;
    6. Chronic and/or recurrent infections, which according to the Investigator’s discretion might pose a risk to the patient's safety;
    7. Major surgery 8 weeks prior to Screening;
    8. Other investigational drug administration within 12 weeks or 5-times the terminal serum half-life, whichever is longer prior to Screening;
    9. Participation in other interventional clinical study (including follow-up and/or study extension) within 12 weeks prior to Screening;
    10. Hypersensitivity to the active substance or to any of the excipients or to murine proteins;
    11. Female patients nursing (women should not breastfeed for 12 months following rituximab treatment);
    12. Any condition or circumstance which in the opinion of the Investigator may make the patient unlikely to complete the study or comply with study procedures and requirements or may pose a risk to the patient's safety;
    13. Any patient who has a disease state or condition that in the opinion of the Investigator could confound the results of the study;
    E.5 End points
    E.5.1Primary end point(s)
    Pharmacokinetic Parameter: Area under the serum concentration versus time curve, from time 0 to last data point above the limit of quantitation during the Treatment Period (AUC)0-tlast.
    E.5.1.1Timepoint(s) of evaluation of this end point
    This endpoint will be evaluated during the treatment period on visits Baseline, day 3, day 15, day 17, day 29, day 57, day 85 and day 169.
    E.5.2Secondary end point(s)
    A. Pharmacokinetic Parameters:
    1. Maximum measured serum concentration over the Treatment Period
    2. Serum AUC(0-inf) during the Treatment Period
    3. Apparent terminal elimination half-life after the second IMP administration, during the Treatment Period
    4. Apparent terminal elimination rate constant after the second IMP administration, during the Treatment Period
    5. Total volume of distribution during the Treatment Period
    6. Total body clearance during the Treatment Period
    B. Pharmacodynamic parameters:
    7. CD19+ B-cell count
    8. IgM levels
    9. IgG, IgA levels
    10. RF, anti-CCP levels
    C. Efficacy Parameters:
    11. Change in disease activity compared to Baseline, as measured by change in DAS28
    12. Change in disease activity compared to Baseline, as measured by change in Clinical Disease Activity Index value
    13. Change in disease activity compared to Baseline, as measured by change in Simplified Disease Activity Index value
    14. EULAR response
    15. Proportion of patients achieving low disease activity
    16. Proportion of patients achieving remission
    17. ACR20, ACR50, and ACR70 response
    D. Safety parameters:
    18. Adverse events
    19. Immunogenicity: serum anti-rituximab antibody
    20. Other safety parameters
    E.5.2.1Timepoint(s) of evaluation of this end point
    Endpoints will be assessed during the whole study till Day 169 of the third retreatment course (days 1, 3, 8, 15, 17, 29, 57, 85, 113, 141 and 169 of the treatment period and days 15, 85 and 169 of each retreatment course). Please note not all endpoints will be assessed on each of the visits.
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence Yes
    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) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study Yes
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Biosimilar trial phaseI/III (comparative pharmacokinetic, pharmacodynamic, efficacy and safety)
    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 Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    After primary endpoint evaluation on day 169 of the treatment period the study will be open label
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA40
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Austria
    Belgium
    Czech Republic
    Estonia
    Germany
    Hungary
    Israel
    Poland
    Romania
    Russian Federation
    Spain
    Ukraine
    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 years2
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months10
    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: 128
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 14
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 90
    F.4.2.2In the whole clinical trial 142
    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)
    None
    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 Decision2015-01-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-11-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-04-24
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA