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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43845   clinical trials with a EudraCT protocol, of which   7282   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:2014-003453-34
    Sponsor's Protocol Code Number:201755
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-05-26
    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 ConcernedGermany - PEI
    A.2EudraCT number2014-003453-34
    A.3Full title of the trial
    A Phase IIb, Double-Blind, Placebo-Controlled, Dose-Adaptive, Study of the Efficacy and Safety of GSK3196165 in Combination with Methotrexate Therapy, in Subjects with Active Moderate-Severe Rheumatoid Arthritis Despite Treatment with Methotrexate.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of a new drug’s effect in people with rheumatoid arthritis who have not responded sufficiently well to treatment with Methotrexate.
    A.4.1Sponsor's protocol code number201755
    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 SponsorGlaxoSmithKline Research & Development 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 supportGlaxoSmithKline Research & Development Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline Research & Development Ltd
    B.5.2Functional name of contact pointGSK Clinical Support HelpDesk
    B.5.3 Address:
    B.5.3.1Street AddressIron Bridge Rd
    B.5.3.2Town/ cityStockley Park West, Uxbridge, Middlesex
    B.5.3.3Post codeUB11 1BU
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44208 9904466
    B.5.5Fax number+44208 9904968
    B.5.6E-mailGSKClinicalSupportHD@gsk.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.3.2Product code GSK3196165
    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 INNINN not available
    D.3.9.1CAS number 1638332-55-4
    D.3.9.2Current sponsor codeGSK3196165
    D.3.9.3Other descriptive nameAnti human granulocyte-macrophage colony-stimulating factor (GM-CSF) monoclonal antibody
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    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, systemic inflammatory autoimmune disease, characterised by a symmetrical polyarthritis that is associated with substantial disability and morbidity
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    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 the efficacy of GSK3196165
    E.2.2Secondary objectives of the trial
    To assess
    - Dose-efficacy response of GSK3196165
    - Safety
    - Population pharmacokinetics
    - Pharmacodynamics
    - Novel biomarkers:
    - To examine the molecular profiles of blood samples to identify factors that may influence biological and clinical
    responses to GSK3196165 and/or associated with the development or progression of RA or medically related
    conditions
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Actigraphy substudy
    To explore how actigraphy measurements of physical activity correlate to disease activity, the following measures will be explored as change over time and change from baseline:
    - Inter- and intra-daily measures of physical activity including but not limited to:
    - Time spent sedentary (sitting and lying), time spent active (walking and standing), total activity score (function of duration and intensity of activity), number and duration of continuous walking periods
    - Duration of morning stiffness
    - Measures of sleep quality including but not be limited to:
    - Time lying, number of movement episodes, sleep efficiency (function of % of movement time and total % of lying time) and fragmentation index (function of movement time % andnumber of movement episodes)
    - RA Symptom and Impact diary
    E.3Principal inclusion criteria
    1. Age ≥18 years at the time of signing informed consent.
    2. Meets ACR/EULAR 2010 RA Classification Criteria.
    3. Functional class I, II or III defined by the 1992 ACR Classification of Functional Status in RA.
    4. Disease duration of ≥12 weeks (time from onset of patient-reported symptoms of either pain or stiffness or swelling in hands, feet or wrists).
    5. Swollen joint count of ≥4 (66-joint count) and tender joint count of ≥
    4 (68-joint count) at screening and at Day 1.
    6. DAS28(CRP) ≥3.2 at screening and DAS28(ESR) ≥3.2 at Day 1.
    7. C-Reactive Protein (CRP) ≥5.0 mg/L at screening.
    8. Must have previously received MTX (15-25 mg weekly) for at least 12 weeks before screening, with no change in route of administration, with a stable and tolerated dose for ≥4 weeks prior to Day 1. A stable dose of MTX ≥7.5 mg/week is acceptable, if the MTX dose has been reduced for reasons of documented intolerance to MTX, e.g. hepatic or hematologic toxicity, or per local requirement.
    9. Weight ≥45 kg.
    10. Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria detailed in Appendix 12.2.
    11. Written informed consent prior to any of the screening procedures including discontinuation of prohibited medications.
    12. Willing to continue or initiate treatment with oral folic acid (at least 5 mg/week) or equivalent and be treated during the entire study (mandatory co-medication for MTX treatment).
    13. Diffusing capacity of the lung for carbon monoxide (DLCO) ≥60%a,b predicted; forced expiratory volume in 1 second (FEV1) ≥70% predicted.
    a. Screening and Day 1 values within 10% of each other (the test may be repeated twice within the screening period,
    i.e. subjects may undergo a total of three DLCO tests during the screening period).
    b. For subjects with DLCO values >60% to <70%, a baseline chest HRCT must be performed during the
    screening period, and it is recommended that the subject be reviewed by a local pulmonologist to exclude significant
    pre-existing respiratory disease.
    c. Germany only: subjects must have DLCO ≥70% predicted (Inclusion Criterion 13b and potential requirement for chest HRCT in Section 5.3.2.2., Section 7.1. and Section 7.4.1. are therefore not applicable).
    14. No evidence of active or latent infection with Mycobacterium tuberculosis (TB), as defined by all of the following:
    a. No history of active or latent TB infection irrespective of treatment status.
    b. A negative diagnostic TB test within 28 days of baseline (Day 1)
    defined as:
    i. A negative QuantiFERON Gold test or T-spot test (performed locally)
    (NB: 2 successive indeterminate QuantiFERON tests will be considered as a positive result).
    OR
    ii. If QuantiFERON gold or T-spot test not approved or registered in country of participation, then a negative tuberculin skin test (TST) reaction as per local guidelines is required (it is strongly recommended that subjects with a history of BCG vaccination be tested with QuantiFERON gold test).
    c. Chest X-ray within 12 weeks of Day 1, locally read by a radiologist, with no evidence of current or previous pulmonary tuberculosis.
    NB: If there has been recent close contact with persons who have active
    TB prior to study enrolment the subject will be referred to a TB physician to undergo additional evaluation.
    E.4Principal exclusion criteria
    1. Pregnant or lactating women.
    2. History of other inflammatory rheumatological or autoimmune disorders, other than Sjögren’s syndrome secondary to RA.
    3. History of any respiratory disease which (in the opinion of the investigator) would compromise subject safety or the ability of the subject to complete the study (e.g. significant interstitial lung disease, such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), moderate-severe asthma, bronchiectasis, previous PAP).
    4. Clinically-significant or unstable (in the opinion of the investigator) persistent cough or dyspnea that is unexplained.
    5. QTc >450msec or QTc >480msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF).
    6. Liver function tests: alanine aminotransferase (ALT) >1.5x upper limit of normal (ULN); aspartate transaminase (AST) >1.5 upper limit of normal; alkaline phosphatase and bilirubin ≥1.5xULN (isolated bilirubin >1.5xULN is acceptable if
    bilirubin is fractionated and direct bilirubin <35%).
    7. Current active liver or biliary disease (with the exception of Gilbert’s syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
    8. Significant unstable or uncontrolled acute or chronic disease (e.g., cardiovascular including uncompensated congestive cardiac failure NYHA III or IV, myocardial infarction within 12 months, unstable angina pectoris, uncontrolled hypertension, uncontrolled hypercholesterolemia) pulmonary, hematologic, gastrointestinal (including Crohn’s Disease or ulcerative colitis), hepatic, renal, neurological, psychiatric, malignancy, endocrinological or infectious diseases, which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.
    9. A history of malignant neoplasm within the last 10 years or breast cancer within the last 20 years, except for non-melanoma skin cancers that have been excised and cured or carcinoma in situ of the uterine cervix.
    10. Kidney disease: Current or history of renal disease, or estimated creatinine clearance <60 mL/min/1.73m2 or serum creatinine >1.5xULN within 28 days of Day 1.
    11. Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.
    12. History of infected joint prosthesis at any time, with the prosthesis still in situ.
    History of leg ulcers, catheters, chronic sinusitis or recurrent chest or urinary tract infections.
    13. Active infections, or history of recurrent infections (excluding recurrent fungal infections of the nail bed), or have required management of acute or chronic infections, as follows:
    a. Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus,
    herpes simplex virus, herpes zoster and atypical mycobacteria).
    OR
    b. Hospitalization for treatment of infection within 26 weeks of Day 1.
    OR
    c. Use of parenteral (IV or IM) antimicrobials (antibacterials, antivirals, antifungals, or antiparasitic agents) within 26
    weeks of Day 1 or oral antimicrobials within 14 days of Day 1.
    14. A vaccination (live or attenuated) within 30 days of Day 1 or BCG vaccination within 365 days of Day 1, or a live vaccination planned during the course of the study.
    15. Any surgical procedure, including bone or joint surgery/synovectomy within 12 weeks prior to Day 1 or any planned surgery within the duration of the study or follow-up period.
    16. For those subjects in the actigraphy substudy: wheelchair, walking aids, artificial limbs; history of severe skin allergy; active implantable device; pacemaker
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of subjects who achieve DAS28(CRP) remission (DAS28(CRP) <2.6)
    E.5.1.1Timepoint(s) of evaluation of this end point
    At Week 24
    E.5.2Secondary end point(s)
    Major Secondary Efficacy Endpoints
    - Change from baseline in DAS28(CRP) at Week 12 (to support dose response evaluation).
    - Proportion of subject achieving DAS28(CRP) remission at all assessment timepoints.
    - Change from baseline in DAS28(CRP) at all assessment timepoints.
    - Time to first DAS28(CRP) remission.
    - Proportion of subjects achieving categorical DAS28(CRP) response (moderate/good EULAR response) at all assessment
    timepoints.
    - ACR 20/50/70 response rates at all assessment timepoints.
    - Index- and Boolean-based ACR/EULAR remission rates, and CDAI remission rate at all assessment timepoints.
    - Change from baseline in SDAI and CDAI at all assessment timepoints.
    - Change from baseline in HAQ-DI score at all assessment timepoints.
    - Change from baseline in pain score at all assessment timepoints.
    - Change from baseline in physical and mental component scores and in domain scores of SF-36 at all assessment timepoints.
    - Change from baseline in FACIT-Fatigue at all assessment timepoints.
    - Change from baseline in BFI Question 3 at all assessment timepoints.

    Major Secondary Safety Endpoints
    - Incidence of adverse events and serious adverse events.
    - Incidence of infections.
    - Incidence of pulmonary events.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Please refer to section 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 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 Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity
    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) 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) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial6
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA46
    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
    Bulgaria
    Canada
    Czech Republic
    Estonia
    Germany
    Hungary
    Italy
    Mexico
    Poland
    Russian Federation
    South Africa
    Spain
    Ukraine
    United Kingdom
    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 years2
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days8
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days12
    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: 179
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 31
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2015-05-26. Yes
    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 state34
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 134
    F.4.2.2In the whole clinical trial 210
    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 investigator is responsible for ensuring that consideration has been given to the post-study care of the subject’s medical condition, whether or not GSK is providing specific post-study treatment
    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 Decision2015-10-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-10-06
    P. End of Trial
    P.End of Trial StatusCompleted
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 19 08:17:40 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA