None listed
Conditions
Brief summary
LTI-01, the study drug being researched in this project, is an experimental treatment being developed by Lung Therapeutics, Inc. This means that it is not an approved treatment in Australia, and is not yet approved anywhere else in the world. LTI-01 is a treatment that is intended to either prevent or remove the build-up in the pleural space around the lungs (called ‘loculation’) and so promoting drainage of the fluid with the goal of avoiding the need for surgery. Study participants will be given 1 dose of LTI-01 a day for up to 3 days in a row. LTI-01 will be administered directly into the pleural or lung cavity through a chest tube. During and after treatment, participants will be assessed for the following: * how safe and well tolerated the LTI-01 is at the dose they are given * how much of the LTI-01 drug is in your blood at specific times to measure the way the body is processes it * the effect of the LTI-01 drug has on your body
Interventions
This is a prospective, open-label, dose escalation safety trial. Patients who present with symptoms consistent with pneumonia along with CPE/empyema will be initially treated by standard of care, including placement of chest tube and initiation of antibiotics, and will be evaluated for participation in this study. Eligible subjects will be appropriately consented to the study and will begin treatment with intrapleural LTI-01 within 24 hr of enrolment.
Subjects will be treated according to their
This is a prospective, open-label, dose escalation safety trial. Patients who present with symptoms consistent with pneumonia along with CPE/empyema will be initially treated by standard of care, including placement of chest tube and initiation of antibiotics, and will be evaluated for participation in this study. Eligible subjects will be appropriately consented to the study and will begin treatment with intrapleural LTI-01 within 24 hr of enrolment. Subjects will be treated according to their assigned dose level daily for up to 3 days. First treatment will begin within 24 hours from initial consent. The study treatment will be administered as a bolus dose through the chest tube into the pleural space and allowed to stay in the space for 3 hours. This treatment will occur once per day for up to 3 consecutive days. Study treatment will occur in a dose escalation format, with up to 5 dose level cohorts. The first 3 subjects enrolled will be given an initial dose of 50,000 IU LTI-01 daily for up to three days. Assuming there are no safety issues in these 3 subjects after review of safety data by the Safety Review Committee (SRC), comprising of the Medical Monitor, Study Investigators and the Sponsor, the dose level will be escalated (doubled) in each consecutive group of three subjects with dosing for up to three days at all dose levels. If complete resolution of the pleural process occurs after one or two doses of LTI-01 in any subject, no further LTI-01 will be administered. This escalation (three per dose level) will continue to a maximum dose level of 800,000 IU unless a dose limiting toxicity (DLT) is observed, Clinical activity will be defined as pleural density improvement of 25%, (determined by the reduction of the percentage of pleural density versus the area of the ipsilateral hemithorax) or >50% reduction of pleural density at Day 4 versus baseline randomization radiographic analysis, as confirmed by chest X-ray and via estimation of the volume of the pleural collection by chest CT scanning. Improvement by chest ultrasonographic scoring will also be used to assess efficacy.
Sponsors
Clinical Network Services Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female greater than or equal to 21 years of age 2. A clinical presentation compatible with pneumonia and a parapneumonic effusion 3. Has pleural fluid requiring drainage that is loculated as determined by lateral decubitius or chest CT or by chest ultrasonography, and which is either: * purulent or * gram stain positive or * culture positive or * acidic with a pH <=7.2 or * greater than half the volume of the thoracic cavity . 4. Written informed consent 5. Failure to drain the pleural space within 3 h after tube thoracostomy 6. Hemodynamically stable and not requiring use of intravenous pressor therapy 7. Absence of severe metabolic derangements such as a serum potassium of <6 mEq/L or diabetic ketoacidosis
Exclusion criteria
1. Previous treatment with intra-pleural fibrinolytics for this CPE/empyema 2. Has a known sensitivity to urokinase plasminogen activator 3. Has had a coincidental stroke, a major hemorrhage or major trauma 4. Head trauma or previous stroke 5. History of previous intracranial hemorrhage or symptoms suggestive of possible current intracranial hemorrhage. 6. Vascular puncture at a non-compressible site in the previous 7 days (e.g. subclavian artery, subclavian vein or internal jugular puncture) 7. Elevated blood pressure (systolic >185 mm Hg) or diastolic mm Hg (>110) 8. Active bleeding on examination 9. Acute bleeding diathesis: platelets <100,000 mm3 or therapeutic doses of heparin received within 48h or history of current warfarin therapy; use of other oral anticoagulants including warfarin or Xa or thrombin inhibitors. 10. Known platelet functional disorder or use of antiplatelet therapy including clopidigrel or other antiplatelet agents other than aspirin at any dose. 11. Estimated creatinine clearance of <30 ml/minute or estimated GFR (glomerular filtration rate)<30 ml/minute. 12. PT/PTT> 1.7x control or PT>15 sec. 13. Has had major surgery in the previous 10 days 14. Has had a previous pneumonectomy on the side of infection 15. Patients who are pregnant or lactating (females of childbearing potential must have a negative pregnancy test before randomization) 16. Expected survival less than three months from a different pathology to this empyema (e.g. metastatic lung carcinoma) 17. Known prior ipsilateral fibrothorax 18. Plasma fibrinogen (FGN) level < 150 mg/L 19. Known allergy to rodents
Outcome results
None listed