Prevention and treatment of Acute Respiratory Distress Syndrome (ARDS) and other acute inflammatory conditions MedDRA version: 19.0 Level: SOC Classification code 10038738 Term: Respiratory, thoracic and mediastinal disorders System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 19.0 Level: PT Classification co
Conditions
Interventions
Product Name: GSK2862277
Product Code: GSK2862277
Pharmaceutical Form: Nebulisation solution
INN or Proposed INN: N/A
CAS Number: N/A
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.; Secondary Objective: - 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. ;Primary end point(s): Baseline adjusted change in Pulmonary Vascular Permeability Index on completion of surgery;Timepoint(s) of evaluation of this end point: At the end of surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary 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. ; Timepoint(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 | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trials HelpDesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed