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   41198   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:2012-003194-25
    Sponsor's Protocol Code Number:MabionCD20-001RA
    National Competent Authority:Lithuania - SMCA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-09-24
    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 ConcernedLithuania - SMCA
    A.2EudraCT number2012-003194-25
    A.3Full title of the trial
    Randomized, Double-blind, Parallel-group Comparative Bioequivalence Trial of MabionCD20® (Mabion SA) Compared to MabThera® (rituximab, Roche) in Patients with Rheumatoid Arthritis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Bioequivalence trial of MabionCD20® (Mabion SA) compared to reference product: MabThera® (rituximab, Roche) in Patients with Rheumatoid Arthritis
    A.4.1Sponsor's protocol code numberMabionCD20-001RA
    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 SponsorMabion S.A.
    B.1.3.4CountryPoland
    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 supportMabion S.A.
    B.4.2CountryPoland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMabion Research&Development Centre
    B.5.2Functional name of contact pointClinical Trial Contact Point
    B.5.3 Address:
    B.5.3.1Street AddressFabryczna 17
    B.5.3.2Town/ cityŁódź
    B.5.3.3Post code99-344
    B.5.3.4CountryPoland
    B.5.6E-mailm.matusiak@mabion.eu
    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 nameMabionCD20
    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.3.9.2Current sponsor codeMabionCD20
    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 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.2.1.1.1Trade 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.3.1Product nameMabThera
    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 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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Active Rheumatoid Arthritis
    E.1.1.1Medical condition in easily understood language
    Active Rheumatoid Arthritis
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    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
    To demonstrate biosimilarity between Test Product: MabionCD20® and the Reference Product: MabThera® (rituximab) in patients with active rheumatoid arthritis (RA), based on the percentage of patients in each treatment group achieving the primary efficacy endpoint of a ³ 20% improvement on the American College of Rheumatology score (ACR20) at Week 24
    E.2.2Secondary objectives of the trial
    1.To assess biosimilarity between Test Product: MabionCD20 and the Reference Product: rituximab.
    2. To demonstrate comparative safety and tolerability of a single course of treatment (two infusions spaced two
    weeks apart) of MabionCD20 and rituximab in patients with moderate to severe active RA.
    3. To demonstrate bioequivalence in pharmacokinetic (PK) characteristics between MabionCD20 and rituximab.
    4. To demonstrate safety of MabionCD20 as second cycle treatment after initial rituximab treatment.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Each patient/subject must meet all of the following inclusion criteria to be enrolled in the study:
    1. Able to provide written informed consent after receiving information about benefits and potential risks of the trial, as
    well as details of the insurance covering the subjects participating in the study
    2. Caucasian males and females ³ 18 up to 80 years old
    3. Body Surface Area (BSA) between 1.5 – 2.2 m2 calculated according to the DuBois & DuBois formula : BSA in m2 =
    (Weight (kg) 0.425 x Height (cm) 0.725) x 0.007184
    4. Patients with active rheumatoid arthritis diagnosed according to revised 1987 American Rheumatism Association criteria (Appendix 3), with disease duration minimum 6 months prior to screening visit, who are naive to tumor necrosis factor (TNF) antagonists or any other monoclonal antibody therapies and who have had an inadequate response to an adequate regimen of methotrexate or/and other disease modifying anti-rheumatic drugs (DMARDs);
    5. Patients with moderate to severe active RA defined as the presence of the following:
    · ³ 8 swollen joints and ³ 8 tender joints, observed by a physician at the screening
    · radiographic evidence of ³ 1 joint with define erosion attributable to RA and 2 or more of the following:
    · serum C-reactive protein (CRP) ³ 6 mg/L
    · erythrocyte sedimentation rate (ESR) ³ 28 mm/hr
    · morning stiffness in and around joints lasting longer than 45 minutes
    6. Patients on methotrexate treatment receiving 10-25 mg /week for at least 12 weeks, with the last 4 weeks at a stable
    dose
    7. Negative serum pregnancy test for women of childbearing potential
    8. Female and male (or her/his partner) of childbearing potential willing to use acceptable forms of contraception (e.g.,
    hormonal contraceptive, contraceptive patch, intrauterine device, double- barrier method (condom or diaphragm with
    spermicide, surgical sterilization, partner’s vasectomy) starting from screening and until 12 months following the last
    infusion.
    9. Ability and willingness to comply with the requirements of the study protocol
    E.4Principal exclusion criteria
    Patients meeting any of the following exclusion criteria [12] are not to be enrolled:
    1. History of or current rheumatic autoimmune disease other than RA eg. Juvenile Idiopathic Arthritis (except
    concurrent Sjogren’s syndrome)
    2. History of or current inflammatory joint disease other than RA
    3. American College for Rheumatology functional Class IV disease
    4. History of significant systemic involvement secondary to RA like severe vasculitis, pulmonary fibrosis, Felty’s syndrome or other immunological disorders eg. systemic lupus erythematosus [SLE], scleroderma, inflammatory bowel disease,
    5. Inability to understand the written and verbal instructions, in particular the risks connected with the study
    6. History of psychiatric disorder that would interfere with normal participation in this protocol
    7. Subject has known positive tests for HIV, hepatitis B surface antigen (HBsAg) Anti-HBc antibody, hepatitis C antibody
    8. Serious and uncontrolled coexisting diseases which, in the Investigator's opinion, would preclude subject participation. These may include but are not limited to:
    · Known cardiopulmonary disease, e.g. coronary artery disease, significant cardiac arrhythmias or severe congestive heart failure, i.e. satisfying criteria for the New York Heart Association [NYHA] classes III or IV
    · Serious and uncontrolled pulmonary diseases (chronic, latent and acute infections of the lung, obstructive pulmonary disease)
    · History of or currently treated serious central nervous system/neurological disorders
    · Any neurological (congenital or acquired), vascular or systemic disorder that might affect any of the efficacy assessments, in particular, joint pain and swelling (e.g., neuropathies and neurovasculopathies, Parkinson’s disease, cerebral palsy, diabetic neuropathy)
    · Serious disorders of the renal, hepatic, endocrine, or gastrointestinal system
    · Active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis, sepsis, opportunistic infections) but excluding fungal infections of nail beds
    · History of recurrent clinically significant infection
    · History of tuberculosis or latent tuberculosis tested and confirmed according to the local standards and regulations and/or positive result of Chest X-ray for tuberculosis at screening or within last 6 months prior to screening.
    · History of cancer including solid tumors, haematologic malignancies, without recovery /remission within 5 years prior to screening, except basal cell and squamous cell carcinoma of the skin that have been excised and cured and treated cervical cancer in situ.
    · History of significant cytopenia or other serious bone marrow disorders
    · Primary or secondary immunodeficiency
    · History of drug, alcohol, or chemical abuse within 2 years prior to screening
    · Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
    9. Serious abnormal laboratory findings, specifically:
    · Neutrophil count < 1.500 / μL
    · Platelet count < 75.000 / μL
    · Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times upper limit of normal
    · Hemoglobin <8.0 g/dL
    · IgG below 5.0 mg/mL or IgM below 0.4 mg/mL
    · Any other serious laboratory abnormality
    10. Prior treatment with rituximab, other anti-CD20 mAb, anti-TNF-a drug or any other monoclonal antibodies
    11. Use of systemic glucocorticoids at dose higher than 10mg prednisolone daily or equivalent, within 2 weeks prior to screening and between screening and Day 1
    12. Allergic reaction or intolerance to rituximab, MabionCD20, or any of their components
    13. Severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or previous treatment of any lymphocyte-depleting therapies
    14. Intolerance or contraindications to administration of IV glucocorticoids
    15. Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 12 months after baseline
    16. Recent vaccination, especially live viral vaccinations (< 4 weeks prior to study drug infusion on Day 1)
    17. Blood donation or other blood loss of more than 500 mL within the last two months prior to Screening Visit
    18. Pregnancy or lactation or women planning to get pregnant during the course of the study and/or within 12 months post last study drug infusion.
    19. Lack of peripheral venous access
    20. Participation in a clinical trial during the two months prior to enrolment in the study (exemption – previously failed screening procedures in MabionCD20-001RA trial)
    E.5 End points
    E.5.1Primary end point(s)
    Primary PK Endpoints:
    · AUC(0-t): area under the plasma concentration-time curve from the first administration to final time point at Week 24. The area under the plasma concentration will be calculated by the linear trapezoidal method up to Cmax and by log-linear approximation after Cmax
    · Cmax - second: maximum measured plasma concentration after the second infusion of the treatment cycle

    Efficacy Endpoints:
    - Percentage of patients who achieved an ACR20 at Week 24.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 24
    E.5.2Secondary end point(s)
    Secondary PK Endpoints:
    - Cmax - first: maximum measured plasma concentration after the first infusion of the treatment cycle.
    - Ctrough: plasma concentration just before second study treatment infusion on Day 15
    - AUC(0-∞): The area under the plasma concentration versus time curve from time 0 to infinity. AUC(0-∞) is calculated as the sum of AUC(0-t) plus the ratio of the last measurable plasma concentration to Kel
    - t½ - after second infusion: apparent first-order terminal elimination half life will be calculated as ln(2)/ Kel
    - Volume of distribution at steady state
    - Plasma clearance

    Efficacy secondary endpoints:
    - Percentage of patients who achieved an ACR20
    - Percentage of patients who achieved an ACR50
    - Percentage of patients who achieved an ACR70
    - Mean change from baseline in Disease Activity Score (DAS28 – ESR)
    - Percent of patients with moderate response on the European League Against Rheumatism (EULAR) scale
    - Percent of patients with good response on the European League Against Rheumatism (EULAR) scale
    E.5.2.1Timepoint(s) of evaluation of this end point
    Weeks 4, 8, 12, 16, 20, 24, 48
    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 Yes
    E.6.7Pharmacodynamic Yes
    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
    Biosimilarity
    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 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 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    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
    Georgia
    Lithuania
    Poland
    Romania
    Russian Federation
    Serbia
    Ukraine
    E.8.7Trial has a data monitoring committee Yes
    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 months3
    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 months3
    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: 647
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 216
    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 state37
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 450
    F.4.2.2In the whole clinical trial 863
    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)
    Patients will receive standart medical care after termination of the study.
    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 Decision2013-02-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-10-23
    P. End of Trial
    P.End of Trial StatusCompleted
    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