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   41232   clinical trials with a EudraCT protocol, of which   6757   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:2017-003037-28
    Sponsor's Protocol Code Number:TOPIRA
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-07-22
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2017-003037-28
    A.3Full title of the trial
    Efficacy of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease modifying anti-rheumatic drugs.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Efficacy of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease modifying anti-rheumatic drugs.
    A.3.2Name or abbreviated title of the trial where available
    TOPIRA
    A.4.1Sponsor's protocol code numberTOPIRA
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUniversity Medical Center Utrecht
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportUniversity Medical Center Utrecht
    B.4.2CountryNetherlands
    B.4.1Name of organisation providing supportRoche
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Medical Center Utrecht
    B.5.2Functional name of contact pointRheumatology & Clinical Immunology
    B.5.3 Address:
    B.5.3.1Street AddressHeidelberglaan 100
    B.5.3.2Town/ cityUtrecht
    B.5.3.3Post code3508GA
    B.5.3.4CountryNetherlands
    B.5.4Telephone number31887550459
    B.5.6E-mailreumatologie-research@umcutrecht.nl
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name RoActemra
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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 Solution for injection/infusion in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTOCILIZUMAB
    D.3.9.1CAS number 375823-41-9
    D.3.9.3Other descriptive nameTOCILIZUMAB
    D.3.9.4EV Substance CodeSUB20313
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number162
    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 Prednisone
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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 namePrednisone
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPrednisone
    D.3.9.2Current sponsor codePrednisone
    D.3.9.3Other descriptive namePREDNISONE
    D.3.9.4EV Substance CodeSUB10020MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPREDNISOLONE
    D.3.9.1CAS number 50-24-8
    D.3.9.2Current sponsor codePrednisolone
    D.3.9.3Other descriptive namePrednisolone
    D.3.9.4EV Substance CodeSUB10018MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number5 to 10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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
    RA patients with active RA despite treatment with DMARDs.
    Reumatoïde artritis
    E.1.1.1Medical condition in easily understood language
    RA patients with active RA despite treatment with DMARDs.
    Reuma (reumatoïde artritis)
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.1
    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 assess whether adding TCZ (subcutaneously 162 mg/week) to current csDMARD therapy is more effective in reducing disease activity than adding prednisone (orally 10 mg/day) in a usual care treat-to-target strategy in patients with insufficient response to DMARD therapy (DMARD-IR).
    E.2.2Secondary objectives of the trial
    Secondary Efficacy Objective(s):
    -To compare treatment strategies on drug retention (TCZ vs prednisone), as surrogate measure of drug efficacy and tolerability, and on drug treatment over time.
    -To assess whether TCZ is more effective than prednisone in reaching different criteria for response, clinical remission, and low disease activity; and on reduction of radiographic progression.
    -To compare treatments on costs and effects in a cost-effectiveness analysis

    Secondary Patient-Reported Outcome Objectives:
    -To assess whether TCZ is more effective than prednisone with regard to quality of life, functional ability, fatigue, sleep quality, and anxiety and depression.
    -To compare treatments on costs and quality of life (utility) in a cost-utility analysis

    Secondary Safety Objectives:
    -To assess the occurrence of serious adverse events (SAEs), glucocorticoid-associated AEs and TCZ-associated AEs

    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    HandScan substudy:
    Primary Objective: to assess whether adding TCZ is more effective than adding prednisone using the HandScan score as endpoint.
    Secondary Objective: To assess the clinical utility of the HandScan in comparison with the clinically used disease activity measures to monitor response to prednisone or TCZ treatment.
    E.3Principal inclusion criteria
    • • Able and willing to give written informed consent.
    • Have sufficient knowledge of the Dutch language to be able to comply with the requirements of the study protocol.
    • At least 18 years of age.
    • Diagnosed as having RA and meeting the 2010 ACR/EULAR criteria for RA (Appendix A).
    • Active RA defined by CDAI>10 and at least 1 swollen joint of the 28 joint count.
    • On stable treatment with csDMARDs for ≥ 8 weeks prior to the screening visit.
    • Eligible to start with a biological according to the 2019 EULAR guidelines for management of RA (see appendix L): previous treatment with ≥2 csDMARDs OR previous treatment with ≥1 csDMARD with presence of a prognostically unfavorable factor.
    E.4Principal exclusion criteria
    • Having a contraindication for treatment with systemic GCs (as determined by the treating rheumatologist, in line with regular care).
    • Having a contraindication for treatment with TCZ, as determined by the treating rheumatologist or as described in the Summary of Product Characteristics (SPC) Paragraph 4.3, page 33. ‘Special warnings and precautions for use’ as described in the SPC Paragraph 4.4, page 33, should be strictly followed.
    • Use of systemic GCs (including i.a. GCs) within 4 weeks before the screening visit.
    • Current use of a bDMARD or tsDMARD; i.e. these need to be discontinued before start of study medication. Wash out periods for bDMARDs and tsDMARDs should follow routine care.
    • Treatment with any investigational agent within 4 weeks prior to the screening visit.
    • Having any other inflammatory rheumatic disease than RA., except for secondary Sjögren’s syndrome will be allowed, as well as RA-overlap syndromes that are primarily treated as RA at the time of screening.
    • Female who is pregnant (by anamnesis) or breast feeding, or considering becoming pregnant during the study period.
    E.5 End points
    E.5.1Primary end point(s)
    Change in CDAI from baseline to 12 months
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline to 12 months
    E.5.2Secondary end point(s)
    SECONDARY EFFICACY ENDPOINTS:
    - Change in CDAI from baseline to 6 months
    - Change in SDAI and change in DAS28 from baseline to 12 months.
    - Drug retention rate, defined as the proportion of patients at 12 months on the treatment (TCZ/prednisone) to which they were allocated.
    - Switch rate, defined as the proportion of patients who switched during the study period to treatment of the other arm.
    - Average dose of TCZ or prednisone from baseline up to 12 months.
    - ACR20, ACR50, and ACR70 response (using 28 joint counts), EULAR good or moderate response.
    - Proportion of patients reaching a state of clinical remission at any time during the study defined by different criteria: CDAI≤2.8 AND max 1 swollen joint of the 28 joint count, CDAI≤2.8, SDAI≤3, DAS28<2.6, and ACR-EULAR Boolean remission (defined by a tender joint count ≤1, a swollen joint count ≤1, a C-reactive protein ≤1mg/dL, and a patient global assessment ≤1 on a 0-10 scale).
    - Time to reach a state of clinical remission defined by the criteria mentioned before.
    - Proportion of patients reaching at least a state of low disease activity (defined by 2.8<CDAI≤10, 3.3<SDAI≤11, 2.6≤DAS28<3.2,) during the study.
    - Change in Sharp/van der Heijde (SvH) score from baseline to 12 months
    - Change in quality of life from baseline to 12 months (using the EQ5D)
    - Change in functional ability from baseline to 12 months (using the Dutch consensus HAQ)
    - Change in fatigue (using the FACIT-F), sleep quality (using the PSQI) and anxiety and depression (using the HADS) from baseline to 12 months.
    - Direct medical (e.g. GP visits) and non-medical (e.g. travel expenses) costs as well as indirect costs (e.g. productivity loss) using the Health Care Utilisation and Work Productivity Questionnaire, and observed drug use and visits to the rheumatology clinic.
    - Quality Adjusted Life Years (based on EQ5-D utility scores over time).

    SECONDARY SAFETY ENDPOINTS:
    - GC Toxicity Index (GTI) score at 6, 9 and 12 months
    - The proportion of patients reaching ≥1 of the following categories of the GTI:
    o Major increase in BMI
    o Worsening of glucose tolerance despite treatment
    o Worsening hypertension despite treatment
    o Worsening hyperlipidemia despite treatment
    o Decrease in bone density
    o Moderate steroid myopathy or greater
    o Moderate skin toxicity or greater
    o Moderate neuropsychiatric symptoms or greater
    o Grade 3 infection or greater
    o Any category of the Specific List
    - The proportion of patients experiencing ≥1 TCZ-associated AE
    - The proportion of patients experiencing ≥1 SAE
    - The number of AEs of the GTI, of TCZ-associated AE and of SAE per patient
    E.5.2.1Timepoint(s) of evaluation of this end point
    As described in E.5.2.
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others 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) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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 concerned8
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    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: 100
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 20
    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 state120
    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 be treated in regular clinical 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 Decision2019-07-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-10-02
    P. End of Trial
    P.End of Trial StatusOngoing
    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