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   35918   clinical trials with a EudraCT protocol, of which   5893   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).
     
    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:2013-000054-22
    Sponsor's Protocol Code Number:ML28641
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-08-07
    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 ConcernedUK - MHRA
    A.2EudraCT number2013-000054-22
    A.3Full title of the trial
    OPEN-LABEL, PHASE IIIB STUDY TO EVALUATE THE EFFICACY AND SAFETY OF SUBCUTANEOUS TOCILIZUMAB (MONOTHERAPY OR COMBINATION THERAPY WITH METHOTREXATE OR OTHER DMARDS) IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS WHO HAVE AN INADEQUATE RESPONSE TO CURRENT NON-BIOLOGIC DMARD THERAPY OR THE FIRST ANTI-TNF BIOLOGIC AGENT
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    OPEN-LABEL, PHASE IIIB STUDY TO EVALUATE THE EFFICACY AND SAFETY OF SUBCUTANEOUS TOCILIZUMAB (MONOTHERAPY OR COMBINATION THERAPY WITH METHOTREXATE OR OTHER DMARDS) IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS WHO HAVE AN INADEQUATE RESPONSE TO CURRENT NON-BIOLOGIC DMARD THERAPY OR THE FIRST ANTI-TNF BIOLOGIC AGENT
    A.3.2Name or abbreviated title of the trial where available
    ACT-MOVE
    A.4.1Sponsor's protocol code numberML28641
    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 SponsorRoche Products Limited
    B.1.3.4CountryUnited Kingdom
    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 supportRoche Products Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationRoche Products Limited
    B.5.2Functional name of contact pointClinical Projects Group
    B.5.3 Address:
    B.5.3.1Street Address6 Falcon Way, Shire Park
    B.5.3.2Town/ cityWelwyn Garden City
    B.5.3.3Post codeAL7 1TW
    B.5.3.4CountryUnited Kingdom
    B.5.6E-mailwelwyn.cpg_general@roche.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 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 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 nametocilizumab SC
    D.3.2Product code Ro 487-7533/F10-04
    D.3.4Pharmaceutical form Solution for injection
    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.3.9.2Current sponsor codeRO4877533
    D.3.9.3Other descriptive nameRecombinant humanised anti-human monoclonal antibody directed against the IL-6R
    D.3.9.4EV Substance CodeSUB20313
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number180
    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
    Rheumatoid Arthritis
    E.1.1.1Medical condition in easily understood language
    Rheumatoid Arthritis
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    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 for this study is to assess the efficacy of switching to subcutaneous (SC) Tocilizumab (as monotherapy or in combination with MTX or other non-biologic DMARDs) in patients who are currently being treated with have an inadequate response to current non-biologic DMARD therapy or the first anti-TNF biologic agent (as monotherapy or in combination with MTX or other non-biologic DMARDs). Inadequate response to anti-TNF treatment is assessed at Week 24 or after a minimum period of 12 weeks of therapy if permitted by local guidance (either defined by the National Institute for Health and Clinical Excellence (NICE) as a Disease Activity Score 28 (DAS28) improvement of less than 1.2, or patients not achieving a DAS28 of ≤ 3.2 according to a treat-to-target strategy). Efficacy will be measured by DAS28-ESR and Clinical Disease Activity Index (CDAI) at every visit up to Week 52.
    E.2.2Secondary objectives of the trial
    o To evaluate safety & tolerability of SC Tocilizumab over time (as monotherapy or in combination with MTX or other non-biologic DMARDs) comprising AEs, physical examination, vital signs, clinical laboratory assessments, including immunogenicity, in patients with active RA up to wk 52.
    o To assess efficacy of SC TCZ (monotherapy or in combination with MTX or other non-biologic DMARDs) over time using endpoints such as DAS28 ESR, ACR response scores, EULAR response criteria, SDAI or CDAI, TJC/SJC, and patient reported outcomes (PROs) up to wk 52, including onset of action at wk 2.

    o Evaluate proportion of patients who achieve low disease activity, defined by DAS28-ESR ≤ 3.2 with SC Tocilizumab (monotherapy or in combination with MTX or other non-biologic DMARDs) at every visit up to wk 52.
    o Evaluate the proportion of patients who achieve remission defined by DAS28-ESR < 2.6 with SC TCZ (monotherapy or in combination with DMARDs) at every visit up to wk 52.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients must meet the following criteria for study entry:
    1. Able and willing to give written informed consent and comply with the requirements of the study protocol.
    2. Patients at least 18 years of age.
    3. Patients with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria.
    4. Oral corticosteroids (≤10 mg/day prednisone or equivalent) and nonsteroidal anti- inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for ≥4 weeks prior to Baseline.
    5. Permitted non-biologic DMARDs are allowed if at a stable dose for at least 4 weeks prior to Baseline.
    6. Receiving treatment on an outpatient basis, not including Tocilizumab.
    7. Females of childbearing potential and males with female partners of childbearing potential may participate in this study only if using a reliable means of contraception (e.g., physical barrier [patient or partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device) during the study. Females of childbearing potential and males with female partners of childbearing potential must use a reliable means of contraception for at least 3 months following the last dose of TCZ.
    8. If female of childbearing potential, the patient must have a negative pregnancy test at Screening and Baseline visits.
    9.Patients who have an inadequate response to current non-biologic DMARD therapy or the first anti-TNF agent (in monotherapy or in combination with MTX or other non-biologic DMARDs). Inadequate response to anti-TNF treatment is defined as not achieving an adequate response to treatment at 24 weeks or after a minimum period of 12 weeks therapy if permitted by local guidance (timing of assessment according to local clinical practice and no more than 8 weeks post-Week 24) defined by NICE as a DAS28 score improvement of less than 1.2 or patients achieving a 1.2 reduction in DAS28 but not achieving low disease activity (current DAS28 ESR above 3.2) and have not been previously exposed to treatment with tocilizumab.
    E.4Principal exclusion criteria
    A patient will be excluded if the answer to any of the following statements is “yes”.
    General:
    1. Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 6 months following baseline.
    2. Rheumatic autoimmune disease other than RA, including systemic lupus erythematosis, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty’s syndrome). Secondary Sjögren’s syndrome with RA is permitted.
    3. Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis (Appendix 2).
    4. Diagnosis of juvenile idiopathic arthritis or juvenile RA, and/or RA before the age of 16.
    5. Prior history of or current inflammatory joint disease other than RA (e.g., gout, Lyme disease, seronegative spondyloarthropathy including reactive arthritis, psoriatic arthritis, and arthropathy of inflammatory bowel disease).

    Excluded Previous or Concomitant Therapy:
    6. Exposure to Tocilizumab (either IV or SC) at any time prior to Baseline.
    7. Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening.
    8. Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti CD4, anti-CD5, anti CD3, anti CD19, and anti CD20.
    9. Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline.
    10. Intraarticular (IA) or parenteral corticosteroids within 4 weeks prior to Baseline.
    11. Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.
    12. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.

    Exclusions for General Safety:
    13. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies.
    14. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or GI disease.
    15. History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn’s disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose to perforation.
    16. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).
    17. Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening.
    18. Active TB requiring treatment within the previous 3 years. Patients should be screened for latent TB and, if positive, treated following local practice guidelines prior to initiating Tocilizumab. However, if local practice or guidelines allow reference to test results that were obtained prior to the screening period as part of routine clinical practice, this is allowed. Patients treated for TB with no recurrence in 3 years are permitted.
    19. Current liver disease as determined by the investigator.
    20. Positive hepatitis B surface antigen (HbsAg) or hepatitis C antibody.
    21. Primary or secondary immunodeficiency (history of or currently active).
    22. Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematological malignancies and solid tumours, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years.
    23. Pregnant women or nursing (breast feeding) mothers.
    24. Patients with reproductive potential not willing to use an effective method of contraception.
    25. History of alcohol, drug, or chemical abuse within 1 year prior to Screening.
    26. Neuropathies or other conditions that might interfere with pain evaluation.

    Laboratory Exclusion Criteria (at Screening):
    27. Serum creatinine >1.4 mg/dL (124 μmol/L) in female patients and >1.6 mg/dL (141 μmol/L) in male patients.
    28. ALT or AST >1.5 times ULN
    29. Total bilirubin >ULN.
    30. Platelet count <100 x 109/L (100,000/mm3).
    31. Hemoglobin <85 g/L (8.5 g/dL; 5.3 mmol/L).
    32. White blood cells <3.0 x 109/L (3000/mm3).
    33. Absolute neutrophil count (ANC) <2.0 x 109/L (2000/mm3)
    34. Absolute lymphocyte count <0.5 x 109/L (500/mm3).
    E.5 End points
    E.5.1Primary end point(s)
    • Change in DAS28-ESR at every visit up to Week 52
    E.5.1.1Timepoint(s) of evaluation of this end point
    At every visit up to Week 52
    E.5.2Secondary end point(s)
    · ACR response scores at every visit up to Week 52.
    · EULAR response criteria at every visit up to Week 52.
    · Change in SDAI or CDAI at every visit up to Week 52.
    · Change in total TJC and total SJC over time.
    · Proportion of patients and reasons for non-biologic DMARD/ corticosteroid dose reductions and/or discontinuation over time.

    MTX adherence in patients being prescribed the biologic DMARD (bDMARD) in combination with a non-biologic DMARD, by using a special designed “Methotrexate adherence questionnaire” at Baseline, W12, W24, W36 and W52.
    E.5.2.1Timepoint(s) of evaluation of this end point
    · ACR response scores at every visit up to Week 52.
    · EULAR response criteria at every visit up to Week 52.
    · Change in SDAI or CDAI at every visit up to Week 52.
    · Change in total TJC and total SJC over time.
    · Proportion of patients and reasons for non-biologic DMARD/ corticosteroid dose reductions and/or discontinuation over time.

    MTX adherence in patients being prescribed the biologic DMARD (bDMARD) in combination with a non-biologic DMARD, by using a “Methotrexate adherence questionnaire” at baseline (week 0), week 12, week 24, week 36 and week 52
    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 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) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned60
    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
    LPLV
    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 months9
    E.8.9.1In the Member State concerned 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.1.3Elderly (>=65 years) Yes
    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 state160
    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)
    The Sponsor does not intend to provide Tocilizumab or other study interventions to patients after conclusion of the study or any earlier patient withdrawal.

    For patients who wish to remain on TCZ treatment, and for whom the investigator considers continued treatment would be beneficial, they should be able to receive TCZ, following approval of subcutaneous TCZ, via the NHS or NICE/ SMC guidance by the time the study completes.
    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 Decision2013-10-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-09-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-08-04
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA