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    Summary
    EudraCT Number:2010-021184-32
    Sponsor's Protocol Code Number:GP13-201
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-02-06
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2010-021184-32
    A.3Full title of the trial
    A randomized, double-blind, controlled study to evaluate pharmacokinetics, pharmacodynamics, safety and efficacy of GP2013 and rituximab in patients with rheumatoid arthritis refractory or intolerant to standard DMARDs and
    one or up to three anti-TNF therapies
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    GP2013 in the Treatment of RA Patients Refractory to or Intolerant of Standard Therapy
    A.4.1Sponsor's protocol code numberGP13-201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01274182
    A.5.4Other Identifiers
    Name:Novartis study code Number:GPN013A2301
    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 SponsorHexal AG
    B.1.3.4CountryGermany
    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 supportHEXAL AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationHEXAL AG
    B.5.2Functional name of contact pointTamas Shisha
    B.5.3 Address:
    B.5.3.1Street AddressIndustriestr 25
    B.5.3.2Town/ cityHolzkirchen
    B.5.3.3Post code83607
    B.5.3.4CountryGermany
    B.5.4Telephone number+49 8024 476 4717
    B.5.5Fax number+49 8024 476 2979
    B.5.6E-mailtamas.shisha@sandoz.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 nameNA
    D.3.2Product code GP2013
    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 codeGP2013
    D.3.9.3Other descriptive nameNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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 typemonoclonal antibody
    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 Rituxan (INN: Rituximab), brand name in the United States
    D.2.1.1.2Name of the Marketing Authorisation holderGenentech, 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.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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 typemonoclonal antibody
    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
    Refractory rheumatoid arthritis
    E.1.1.1Medical condition in easily understood language
    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 18.0
    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 assess bioequivalence between GP2013 and MabThera®/Rituxan® in combination with MTX in patients with active Rheumatoid Arthritis who have not responded adequately, or have shown intolerance, to DMARDs, including MTX, and one or up to three anti-TNF therapies.
    E.2.2Secondary objectives of the trial
    To evaluate:
    • Additional pharmacokinetic (PK) parameters, pharmacodynamic (PD) and efficacy of GP2013 and MabThera®/Rituxan® in subjects with active RA [ Time Frame: 1.5 years ]
    • Safety and tolerability of GP2013 and MabThera®/Rituxan® in patients with RA [ Time Frame: 1.5 years ]
    For additional secondary objectives please see full protocol
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients eligible for inclusion in this study have to fulfill all of the following criteria:
    1. Patients must give written informed consent before any study-related assessment is performed.
    2. Patients must be ≥ 18 years of age.
    3. Patients must have a diagnosis of Rheumatoid Arthritis, based on the ACR 1987 criteria.
    At least 4 of the following 7 criteria must be fulfilled (and criteria a. through d. must have been present for at least 6 weeks) to confirm the diagnosis of RA:
    a. joint morning stiffness of at least one hour
    b. swelling of joints in at least three joint areas, diagnosed by a doctor, c. swelling of MCP and wrist joints, diagnosed by a doctor
    d. bilateral, symmetric swelling of joints in the same joint areas, diagnosed by a doctor
    e. rheumatoid nodule
    f. rheumatoid factor seropositivity
    g. positive findings in hand radiographs.
    4. Patients must have had the diagnosis of RA for at least 6 months at Visit 2.
    5. Patients must have active RA at baseline (Visit 2):
    • ≥ 6 swollen joints (of 66 joints assessed)
    • ≥ 6 tender joints (of 68 joints assessed)
    • CRP ≥ 10 mg/L
    OR ESR ≥ 28 mm/1st hour
    Note: If one of the above criteria is not met at Visit 2, the patient is not eligible for randomization at this time point. A re-assessment (i.e., an additional Visit 2) can be done once within 14 days at the discretion of the investigator. A patient can repeat the whole screening phase (be re-screened) only once.
    6. Patients must be seropositive for rheumatoid factor (RF) and/or have antibodies to cyclic citrullinated peptide (anti-CCP) at Visit 1.

    For additional inclusion criteria, please refer to section 4.1 of the protocol.
    E.4Principal exclusion criteria
    Patients eligible for inclusion in this study must not fulfill any of the following criteria:
    1. RA patients with functional status class IV classified according to the ACR 1991 revised criteria.
    2. Patients with levels of serum IgG, IgM and IgA below LLN at Visit 1 and/or Visit 2.
    3. Patients with systemic manifestations of RA, with the exception of Sjögren’s syndrome.
    4. Patients taking high potency opioid analgesics (e.g. methadone, hydromorphone, morphine).
    5. Female patients nursing (lactating / breast-feeding), pregnant or planning of pregnancy within 12 months after the last infusion of study drug, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (cut-off as defined by the central laboratory).
    6. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and intrauterine devices (IUDs)). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable.
    7. Patients who have had any therapy with intra-articular injections (e. g. corticoid) required by a flare up to 4 weeks before randomization.

    For additional exclusion criteria, please refer to section 4.2 of the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    The primary PK variable is
    • AUC(0-∞), i.e. the PK profile will be derived over the entire 1st treatment course including both infusions, of GP2013 and MabThera®/Rituxan® concentrations determined in serum samples collected over
    24 weeks.
    The primary analysis will be based on the PAS population in part I of the study and on PAS+A population in part II of the study, with the PAS population used as part of the sensitivity analysis
    E.5.1.1Timepoint(s) of evaluation of this end point
    Primary endpoint determined based on serum samples collected over
    24 weeks.
    E.5.2Secondary end point(s)
    PK parameters: In addition to AUC(0-∞) and Cmax of the 1st infusion the PK parameters
    • AUC(0-14d), AUC(0-12w), AUC(0-24w), Cmax of the 2nd infusion, and tmax (for both infusions), of rituximab (MabThera®/Rituxan®) concentrations determined in serum samples collected over 24 weeks will be assessed.

    PD parameter: • Area under the effect-time curve (AUEC(0-t)) from time 0 (before the 1st infusion) up to the
    2nd infusion (AUEC(0-14d)) as a percent change from baseline value derived by the linear- trapezoidal rule.
    • Percent peripheral B cell levels relative to baseline by visit.
    •Number and % of patients with a B cell count below the limit of quantification by Day 1 (after first infusion), 4, 8, and 15 (before second infusion).

    Please refer to the clinical study protocol for additional details.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Please refer to the clinical study protocol Section 6: Visit schedule and assessmentsfor additional details and Table 6-1: Assessment schedule
    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 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 No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 Yes
    E.8.2.3.1Comparator description
    Rituxan
    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 EEA41
    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
    Argentina
    Austria
    Belgium
    Brazil
    Bulgaria
    Estonia
    Germany
    Hungary
    India
    Italy
    Poland
    Romania
    Russian Federation
    Spain
    Turkey
    United Kingdom
    United States
    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
    A patient will be considered to have completed the study when all scheduled study assessments and procedures up to and including Visit 14 (week 52) or, in case of retreatment with another course of study medication, his/ her 26 weeks safety, efficacy and PD follow-up visit, whichever is later, have been concluded.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months11
    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: 99
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 25
    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 state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 70
    F.4.2.2In the whole clinical trial 124
    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 Decision2015-04-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-02-19
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-11-10
    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
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