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   43865   clinical trials with a EudraCT protocol, of which   7286   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:2014-000643-33
    Sponsor's Protocol Code Number:TFR116341
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2014-07-02
    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 number2014-000643-33
    A.3Full title of the trial
    A Placebo Controlled, Double-blind, Multi-centre, Single Dose, Parallel Group, Randomised Clinical Trial of GSK2862277 in Patients undergoing Oesophagectomy Surgery.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to look at the effect of a drug which blocks the TNFR1 pathway in subjects who undergoing surgery for oesophageal cancer.
    A.3.2Name or abbreviated title of the trial where available
    GSK2862277 PIIa study in oesophagectomy patients
    A.4.1Sponsor's protocol code numberTFR116341
    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 Ltd
    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 and 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 pointClinical Trials HelpDesk
    B.5.3 Address:
    B.5.3.1Street AddressIron Bridge Road
    B.5.3.2Town/ cityUxbridge
    B.5.3.3Post codeUB11 1BU
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44208990 4466
    B.5.5Fax number+44208990 1234
    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.3.1Product nameGSK2862277
    D.3.2Product code GSK2862277
    D.3.4Pharmaceutical form Nebulisation solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeGSK2862277
    D.3.9.3Other descriptive nameGSK2862277
    D.3.9.4EV Substance CodeSUB83601
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 placeboNebuliser solution
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Prevention and treatment of Acute Respiratory Distress Syndrome
    (ARDS) and other acute inflammatory conditions
    E.1.1.1Medical condition in easily understood language
    Prevention and treatment of Acute Respiratory Distress Syndrome
    (ARDS)
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level SOC
    E.1.2Classification code 10038738
    E.1.2Term Respiratory, thoracic and mediastinal disorders
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level PT
    E.1.2Classification code 10069351
    E.1.2Term Acute lung injury
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary: To evaluate whether a single nebulised dose of GSK2862277 prevents peri-operative lung injury compared to placebo, as assessed by measurement of pulmonary vascular permeability.
    E.2.2Secondary objectives of the trial
    - To evaluate whether a single nebulised dose of GSK2862277 prevents perioperative lung injury compared to placebo, as assessed by measurement of pulmonary oedema.
    - To evaluate the safety and tolerability of GSK2862277 administered preoperatively.
    - To evaluate whether a single nebulised dose of GSK2862277 prevents perioperative lung injury compared to placebo, as assessed by degree of hypoxaemia.
    - To evaluate differences in expression profile of BAL biomarkers from both ventilated and collapsed lungs immediately after surgery.
    - To evaluate the effect of a single IH dose of GSK2862277 compared to placebo, on attenuating lung and distal organ injury over the post-operative period.
    - To describe plasma pharmacokinetics of a single inhaled dose of GSK2862277.
    - To quantify the concentration of GSK2862277 in BAL and to compare to plasma levels of GSK2862277.
    - To evaluate the levels and specificity of any anti-drug antibodies formed following dosing with GSK2862277.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject has a planned elective transthoracic oesophagectomy
    2. Male or female between 18 and 80 years of age inclusive, at the time of signing the informed consent.
    3. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
    4. A female subject is eligible to participate if she is of:
    - Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods listed in the appendix of this concept protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks should elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT.
    Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
    5. Liver parameters according to the thresholds below: AST and ALT < 3xULN; alkaline phosphatase and bilirubin =< 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
    6. QTcB or QTcF <= 450 msec at screening. Either QTcB or QTcF, machine or manual over-read can be used. This applies to both males and females. The QT correction formula used to determine inclusion and discontinuation for an individual subject should be the same throughout the study.
    - Based on average QTc value of triplicate ECGs obtained over a brief recording period.
    It is recognised that in some subjects the QTc may be variable over time (e.g. intermittent use of a pacemaker; junctional rhythm). Inclusion of these subjects should be discussed with the medical monitor prior to enrolment.
    E.4Principal exclusion criteria
    1. Positive screening test for pre-existing antibodies that bind GSK2862277.
    2. Current evidence or history of pneumonia within 14 days before dosing.
    3. Diagnosis of chronic respiratory disease with a forced expiratory volume in one second (FEV1) less than 50% predicted or resting oxygen saturations of less 92%.
    4. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK
    Medical Monitor, contraindicates their participation.
    5. The subject has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the
    duration of the biological effect of the investigational product (whichever is longer).
    6. Use of corticosteroids (IV, oral or IM) at a dose of > 10 mg/day prednisolone (or equivalent) within 14 days prior to dosing, or anti-Tumor Necrosis Factor (anti-
    TNF) or anti-Interleukin-1 (anti-IL1) within 60 days prior to dosing.

    Criteria Based Upon Medical Histories
    1. History or current evidence of clinically significant renal disease, diabetes mellitus/metabolic syndrome, hypertension, peripheral vascular disease or any other
    clinically significant respiratory, cardiovascular, neurological, endocrine, or hematological abnormalities that are uncontrolled on permitted therapy. Significant
    is defined as any disease that, in the opinion of the Investigator, would put the safety of the patients at risk through study participation, or which would affect the safety analysis or other analysis if the disease/condition exacerbated during the study.
    2. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
    3. History of regular alcohol consumption within 6 months of the study, defined as:
    - an average weekly intake of >28 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml)
    of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.

    Criteria Based Upon Diagnostic Assessments
    1. Screens positive for Hepatitis B surface antigen, Hepatitis C antibody
    2. Known Human Immunodeficiency Virus (HIV) positive; testing will be conducted in accordance with local procedures
    3. Tests positive for Mycobacterium tuberculosis using QuantiFERON Gold Test.
    Other Criteria
    1. Subject has received a live attenuated vaccine(s) within 3 weeks of randomisation or will require vaccination with a live attenuated vaccine prior to the end of the study (Day 28).
    2. Unwillingness or inability to follow the procedures outlined in the protocol.
    3. Subject is mentally or legally incapacitated.
    E.5 End points
    E.5.1Primary end point(s)
    Baseline adjusted change in Pulmonary Vascular Permeability Index on completion of surgery
    E.5.1.1Timepoint(s) of evaluation of this end point
    At the end of surgery
    E.5.2Secondary end point(s)
    - Baseline adjusted change in EVLWI on completion of surgery.
    - AEs
    - Clinical laboratory safety data.
    - ECG readings
    - Vital signs
    - Baseline adjusted change in PaO2/FiO2 on completion of surgery.
    - Levels of BAL biomarkers (e.g. IL-6, sRAGE, protein levels) on completion of surgery.
    - Change over time in PaO2/FiO2 post-operatively on Day 2 through to Day 4 (as available; SpO2/FiO2 when arterial line removed)
    - Change over time in PVPI and EVLWI post-operatively on Day 2 through to Day 4
    - Daily SOFA scores on Day 2 through to Day 4
    - Plasma concentrations of GSK2862277 and derived pharmacokinetic parameters.
    - BAL concentrations of GSK2862277 and derived pharmacokinetic parameters
    - Ratio of BAL concentration to plasma concentration.
    - Incidence and titers of serum anti-GSK2862277 antibodies post dosing.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. At the end of surgery and post-operatively through to Day 4
    2. At the end of surgery
    3. Days 2-4 post surgery
    4. Days 2-4 post surgery
    5. Daily from Days 2 to 4
    6. 1hr post dosing; on completion of surgery and 24h post-dosine
    7. Baseline, Day 8 and Day 28
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    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
    Biomarkers
    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 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 concerned5
    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 years2
    E.8.9.1In the Member State concerned months0
    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 months0
    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: 75
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 5
    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 state80
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 80
    F.4.2.2In the whole clinical trial 80
    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)
    Once subjects have completed the study they will return to normal standard of care treatment for a patient with oesophageal cancer.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Comprehensive Clinical Research Network (CCRN)
    G.4.3.4Network Country United Kingdom
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-08-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-08-26
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2017-08-09
    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 26 18:21:46 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA