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    Summary
    EudraCT Number:2013-004555-21
    Sponsor's Protocol Code Number:CT-P103.2
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-01-23
    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 ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2013-004555-21
    A.3Full title of the trial
    A Randomized, Controlled, Double-Blind, Parallel-Group, Phase 3 Study to Compare the Pharmacokinetics, Efficacy and Safety between CT-P10, Rituxan and MabThera in Patients with Rheumatoid Arthritis
    Randomizált, kontrollos, kettős-vak, párhuzamos csoportos elrendezésű, III. fázisú vizsgálat a CT-P10, a Rituxan és a MabThera farmakokinetikájának, hatékonyságának és biztonságosságának összehasonlítására reumatoid arthritis-ben szenvedő betegeknél
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    This is a Phase 3 Study to Compare the Pharmacokinetics, Efficacy and Safety between CT-P10, Rituxan and MabThera in Patients with Rheumatoid Arthritis
    A.4.1Sponsor's protocol code numberCT-P103.2
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02149121
    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 SponsorCELLTRION, Inc.
    B.1.3.4CountryKorea, Republic of
    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 supportCELLTRION, Inc
    B.4.2CountryKorea, Republic of
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCELLTRION, Inc
    B.5.2Functional name of contact pointClinical Planning Dept.
    B.5.3 Address:
    B.5.3.1Street Address23, Academy-ro, Yeonsu-gu
    B.5.3.2Town/ cityIncheon
    B.5.3.3Post code22104
    B.5.3.4CountryKorea, Republic of
    B.5.4Telephone number+8232850 6532
    B.5.5Fax number+8232850 6593
    B.5.6E-mailSungYoung.Lee@celltrion.com
    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 nameCT- P10
    D.3.2Product code CT- P10
    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 milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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.2.1.1.1Trade 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.3.2Product code L01XC02
    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 milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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: 3
    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 Rituxan
    D.2.1.1.2Name of the Marketing Authorisation holderBiogen Idec Inc and Genentech USA Inc
    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 nameRituxan
    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 milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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
    Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes
    inflammation and deformity of the joints. Other problems may also develop, including inflammation in various parts of the body.
    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 18.0
    E.1.2Level HLT
    E.1.2Classification code 10039075
    E.1.2Term Rheumatoid arthritis and associated conditions
    E.1.2System Organ Class 100000004870
    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 of Part 1 of the study is:
    "To evaluate and compare pharmacokinetics in terms of area under the serum concentration-time curve from zero to time of last quantifiable concentration (AUC0-last), AUC from zero to infinity (AUC0-∞) and maximum serum concentration (Cmax) (after the second infusion) of CT-P10 to Rituxan, CT-P10 to MabThera and Rituxan to MabThera during the first course of treatment (over the first 24 weeks)."

    The primary objective of Part 2 of the study is:

    • To demonstrate that CT-P10 is similar to reference products (Rituxan and MabThera) in terms of efficacy as determined by clinical response according to change from Baseline in disease activity measured by Disease Activity Score using 28 joint counts (DAS28) (C-reactive protein [CRP]) at Week 24.
    E.2.2Secondary objectives of the trial
    The secondary objectives of Part 1 of the study are:
    • To assess the additional PK variables of CT-P10, Rituxan and MabThera during the first course of treatment (over the first 24 weeks).
    • To evaluate the pharmacodynamics and safety of CT-P10, Rituxan and MabThera (over the first 24 weeks).

    The secondary objective of Part 2 of the study is:
    • To evaluate the additional PK (up to Week 48), efficacy, PD, overall safety, and biomarkers of CT-P10 compared with reference products.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Each patient must meet all of the following criteria to be enrolled in this study:
    1. Patient is male or female between 18 and 75 years old, inclusive.
    2. Patient has a diagnosis of RA according to the revised 1987 ACR classification criteria (Arnett et al 1988) for at least 6 months prior to randomization.
    3. Patient has active disease as defined by the presence of 6 or more swollen joints (of 66 assessed) and 6 or more tender joints (of 68 assessed), and serum CRP ≥1.5 mg/dL (≥15 mg/L) or an ESR ≥28 mm/hour.
    4. Patient has experienced an inadequate response to previous or current treatment with the anti-TNF agents infliximab (≥3 mg/kg; at least 3 infusions for at least 3 months), golimumab (50 mg once a month for at least 12 to 14 weeks or 2 mg/kg IV infusion for at least 3 months), adalimumab (40 mg every other week for at least 3 months), or etanercept (25 mg twice weekly or 50 mg once weekly for at least 3 months), or was intolerant to at least 1 administration of these agents. Patients who discontinued etanercept for at least 4 weeks, infliximab or adalimumab for at least 8 weeks, or golimumab for at least 10 weeks prior to randomization are permitted to enter the study.
    Patients who received any other anti-TNF agents not in this list can be enrolled if the patient discontinued the treatment at least 4 weeks or 5 half-lives prior to randomization, whichever is longer.
    5. Patient has a proper discontinuation period after treatment with interleukin-1 receptor (IL-1R) antagonist, interleukin-6 receptor (IL-6R) antibody, or abatacept. Patients who discontinued IL-1R antagonist for at least 4 weeks, abatacept for at least 8 weeks, or IL-6R antibody for at least 17 weeks prior to randomization are permitted to enter the study.
    Patients who had any other biological drugs not in this list can be enrolled if the patient discontinued the treatment at least 4 weeks or 5 half-lives prior to randomization, whichever is longer.
    6. Patient has received MTX treatment (7.5 to 25 mg/week orally or parenterally) for at least the past 12 weeks, with the last 4 weeks at a stable dose before Screening.
    7. Patient has the following hematology laboratory test results at Screening:
    • Hemoglobin ≥8.0 g/dL
    • White blood cell count ≥3.5 × 10 3 cells/μL (SI [Système International d'Unités] units: ≥3.5 × 10 9 cells/L)
    • Neutrophil count ≥1.5 × 10 3 cells/μL (SI units: ≥1.5 × 10 9 cells/L)
    • Platelet count ≥75× 10 3 cells/μL (SI units: ≥75 × 10 9 cells/L)
    8. Patient has adequate renal and hepatic function at Screening as defined by the following clinical chemistry results:
    • Serum creatinine <1.5 × upper limit of normal (ULN) or an estimated creatinine
    clearance level >50 mL/min (by Cockcroft-Gault formula)
    • Serum alanine aminotransferase <2.5 × ULN
    • Serum aspartate aminotransferase <2.5 × ULN
    • Serum total bilirubin <2 × ULN
    9. Patient has the ability to comprehend the full nature and purpose of the study, including possible risks and side effects, to cooperate with the investigator, to understand verbal and/or written instructions, and to comply with the requirements of the entire study.
    10. Patient (or legal guardian, if applicable) has been informed of the full nature and purpose of the study, including possible risks and side effects, and given ample time and opportunity to read and understand this information, and provide signed and dated written informed consent before inclusion in the study.
    11. For both male and female patients, the patient and their partners of childbearing potential either agree to practice total abstinence or use 2 of the following medically acceptable methods of contraception during the course of the study and for 12 months following discontinuation of study drug (excluding women who are not of childbearing potential and men who have been sterilized):
    • Barrier contraceptives (male condom, female condom, or diaphragm with a
    spermicidal gel)
    • Hormonal contraceptives (implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings)
    • Intrauterine device
    Male and female patients and their partners who have been surgically sterilized for less than 6 months prior to the date of informed consent must agree to use 2 medically acceptable methods of contraception or to practice total abstinence.
    Menopausal females must have experienced their last period more than 12 months prior to the date of informed consent to be classified as not of childbearing.
    E.4Principal exclusion criteria
    Patients meeting any of the following criteria will be excluded from the study:
    1. Patient has taken more than 2 biologic agents.
    2. Patient has previously been administered Rituximab or participated in a Rituximab biosimilar study.
    3. Patient has allergies or hypersensitivity to murine, chimeric, human, or humanized proteins.
    4. Patient has current or past history of chronic infection with hepatitis B, hepatitis C, or infection with human immunodeficiency virus (HIV)-1 or -2 or who has a positive result to the screening test for these infections.
    5. Patient has an infection requiring oral antibiotics 2 weeks before randomization,
    parenteral injection of antibiotics 4 weeks before randomization, other serious infection 6 months before randomization, a history of recurrent herpes zoster or other chronic or recurrent infection 6 weeks before randomization.
    6. Patient has a past or current diagnosis of tuberculosis (TB), recent exposure to person with active TB, examination findings indicating the presence of TB, defined as a positive result for interferon-γ release assay, or other severe or chronic infection (such as sepsis, abscess or opportunistic infection, or invasive fungal infection such as histoplasmosis). A patient who has a past diagnosis with sufficient documentation of prophylaxis or complete resolution following treatment can be enrolled.
    7. Patient is receiving any of the following medications or therapies:
    • Previous treatment within 6 months of IV gamma globulin or the Prosorba Column
    • Any surgical procedure, including bone or joint surgery or synovectomy (including
    joint fusion or replacement) within 12 weeks prior to randomization or planned within 6 months after randomization
    • Intra-articular corticosteroids within 8 weeks prior to randomization. Patients are permitted to receive either oral or parenteral glucocorticoids (≤10 mg daily of
    prednisone/prednisolone or equivalent), and nonsteroidal anti-inflammatory drug, if they have received a stable dose for at least 4 weeks prior to randomization. In
    addition, patients are permitted to receive low potency topical, otic, and ophthalmic glucocorticoid preparations provided the preparations are administered per the instructions on the product label.
    • Disease-modifying antirheumatic drugs, other than MTX, including
    hydroxychloroquine, chloroquine, or sulfasalazine, within 4 weeks prior to
    randomization. Patients who discontinued leflunomide and have had successful
    chelation with 8 g of cholestyramine (3 times daily) for 11 days must wait 4 weeks
    prior to randomization. Patients who discontinued leflunomide and did not have a
    cholestyramine discontinuation period must wait 12 weeks after last dose of
    leflunomide before randomization.
    • Live or live-attenuated vaccine within 8 weeks prior to randomization, and killed
    vaccines within 4 weeks prior to randomization
    • History of any biologic agent causing B-cell depletion or targeting B-cells
    8. Patient has a medical condition including one or more of the following:
    • Uncontrolled diabetes mellitus, even after insulin treatment
    • Uncontrolled hypertension at the discretion of the investigator
    • Any other inflammatory or rheumatic disease, including but not limited to psoriatic arthritis, ankylosing spondylitis, spondyloarthritis, systemic lupus erythematosus, Lyme disease, or fibromyalgia, that may confound the evaluation of the effect of study drug
    • History of any malignancy within the previous 5 years prior to date of informed
    consent except completely excised or cured squamous carcinoma of the uterine cervix, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma
    • History of lymphoma, lymphoproliferative disease, or bone marrow hypoplasia
    • Patients with New York Heart Association class III or IV heart failure, severe
    uncontrolled cardiac disease (unstable angina, arrhythmias, clinically significant
    electrocardiogram [ECG] abnormalities), or myocardial infarction within the previous 6 months prior to date of consent
    • History of organ transplantation, including corneal graft/transplantation
    • Severe physical incapacitation (unable to perform routine self-care), has RA ACR
    functional status class 4, or no expected benefit from medication
    • Any uncontrolled clinically significant respiratory disease (in the opinion of the
    investigator), including but not limited to chronic obstructive pulmonary disease,
    asthma, bronchiectasis, or pleural effusion
    • Previous diagnosis or symptoms suggestive of demyelinating disorders, including
    multiple sclerosis and Guillain-Barré syndrome
    • Any condition significantly affecting the nervous system (i.e., neuropathic conditions or nervous system damage) if it may interfere with the investigator’s assessment of disease assessment scores including joint counts.

    Please Refer to the Protocol Section 4.1.2 Exclusion Criteria for a full list of Exclusion Criteria
    E.5 End points
    E.5.1Primary end point(s)
    The following PK parameters for the study drug (CT-P10, Rituxan and MabThera) will be determined as co-primary PK endpoints in Part 1 (over the first 24 weeks):
    • AUC0-last: area under the serum concentration-time curve covering both infusions, time to the last measurable concentration
    • AUC0-∞: area under the serum concentration-time curve covering both infusions, time zero to infinity
    • Cmax: maximum concentration after the second infusion

    The following efficacy parameter for the study drug (CT-P10 and reference products [ Rituxan and MabThera]) will be determined as the primary efficacy endpoint:
    • The change from Baseline in disease activity measured by DAS28 (CRP) at Week 24
    • The proportion of patients achieving clinical response (according to the ACR20 criteria) at Week 24.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Please refer to E.5.1 and also the protocol
    E.5.2Secondary end point(s)
    The following PK parameters for the study drug (CT-P10, Rituxan and
    MabThera) will be determined as secondary PK endpoints in Part 1 (over
    the first 24 weeks):
    • AUC0-day14: area under the serum concentration-time curve covering
    both infusion, time zero to day 14
    • Vd: volume of distribution
    • CL: total clearance
    • t1/2: terminal elimination half-life after the second infusion
    • Tmax: time to Cmax after both the first and second infusions
    • Cmax, 1: maximum concentration after the first infusion
    • Cmin: concentration at Week 24
    • Ctrough: trough concentration prior to the second infusion
    The following PK parameters for the study drugs (CT-P10 and reference
    products [Rituxan and MabThera]) will be determined as secondary PK
    endpoints in Part 2 (up to Week 48 or over the first 24 weeks if second
    course of treatment is not administered):
    • Tmax: time to Cmax after both the first and second infusions
    • Cmax: maximum concentration after both the first and second
    infusions
    • Cmin: concentration at Weeks 24 and 48
    • Ctrough: trough concentration prior to the second infusion
    The following efficacy parameters for the study drugs will be determined
    as secondary efficacy endpoints:
    • ACR20, ACR50 and ACR 70 at Week 24, Week 48 and Extension Week
    24
    • Individual components of the ACR criteria compared with Baseline at
    Week 24 , Week 48 and Extension Week 24
    • Time to onset of ACR20 response over 24 weeks
    • Mean change from Baseline in disease activity measured by DAS28
    (CRP) at Weeks 12 and 48 and Extension Week 24 and DAS28 (ESR) at
    Weeks 12, 24 and 48 and Extension Week 24
    • Proportion of patients with a good response, defined according to the
    European League Against Rheumatism (EULAR) response criteria at
    Week 24, Week 48 and Extension Week 24
    • Hybrid ACR response at Week 24, Week 48 and Extension Week 24
    • SDAI and CDAI at Week 24, Week 48 and Extension Week 24
    • Joint damage progression based on radiographic evaluations, van der
    Heijde modification of the Sharp scoring system at Week 48, Extension
    Week 24 and the EOS visit
    Functional disability (HAQ disability index) at Week 24, Week 48 and
    Extension Week 24
    • Health-related quality of life (SF-36 health survey score) compared
    with Baseline at Week 24, Week 48 and Extension Week 24
    The following safety parameters for the study drug (CT-P10, Rituxan and
    MabThera) will be determined as secondary safety endpoints:
    • Immunogenicity testing
    • Immunoglobulin (IgM, IgG and IgA) testing
    • Hypersensitivity monitoring via vital sign measurements (including
    blood pressure, heart and respiratory rates, and temperature) and ECGs
    • Vital sign measurements
    • ECGs
    • Signs and symptoms of TB monitoring
    • Physical examination findings
    • AEs
    • Infections
    • Infusion related reactions (IRRs)
    • Clinical laboratory analyses
    • Pregnancy testing
    • Concomitant medications
    The following PD parameters for the study drug (CT-P10, Rituxan and
    MabThera) will be determined as PD endpoints:
    • B-cell kinetics over time including depletion and recovery
    • CRP and ESR at Week 24, Week 48 and Extension Week 24
    • Rheumatoid factor and anti-CCP at Week 24, Week 48 and Extension
    Week 24
    E.5.2.1Timepoint(s) of evaluation of this end point
    Please refer to E.5.2 and also the protocol
    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 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) 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 trial3
    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 concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA70
    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
    Bosnia and Herzegovina
    Brazil
    Bulgaria
    Chile
    Colombia
    Germany
    Greece
    Hungary
    Israel
    Korea, Republic of
    Latvia
    Mexico
    Peru
    Poland
    Portugal
    Romania
    Russian Federation
    Slovakia
    Spain
    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
    The date when last patient completes the last visit
    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 months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months7
    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.1.2.1Number of subjects for this age range: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 61
    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 state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 110
    F.4.2.2In the whole clinical trial 361
    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)
    Standard of Care
    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 Decision2014-04-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-03-19
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-02-15
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