A Study to Evaluate LTI-01 in Patients With Infected, Non-draining Pleural Effusions

Study Overview
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Brief Summary
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The LTI-01-2001 study is a double-blind, placebo-controlled, Phase 2 study to evaluate LTI-01 (single-chain urokinase plasminogen activator, scuPA) in patients with infected, non-draining pleural effusions.

Official Title
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A Phase 2, Randomized, Placebo-controlled, Double-blind, Dose-ranging Study Evaluating LTI-01 (Single-chain Urokinase Plasminogen Activator, scuPA) in Patients With Infected, Non-draining Pleural Effusions

Conditions
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Pleural Effusion

Intervention / Treatment
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* Drug: LTI-01
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female ≥ 18 years of age who provide written informed consent Clinical presentation compatible with complicated parapneumonic pleural effusion (CPE), empyema or other type of pleural infection Has pleural fluid requiring drainage as determined by chest ultrasonography or by chest CT, and which is either: a) purulent; b) gram stain positive; c) culture positive; d) pH < 7.2; or e) glucose < 60 mg/dL (3.3 mmol/L) Failure to adequately drain pleural fluid ≥ 3 hours post insertion of patent chest tube within the pleural space, as evidenced by one or more of the following criteria: > 2 cm depth of fluid by ultrasound or CT < 80% drainage from chest radiograph obtained prior to chest tube insertion. Key Exclusion Criteria: Current pleural infection already treated with intrapleural fibrinolytic therapy Evidence of ipsilateral fibrothorax (e.g. CT scan with > 0.5 cm visceral pleural thickening) History of multiple thoracenteses or thoracic surgical procedures within 3 months of screening Previous pneumonectomy on the side of the pleural effusion Current bilateral pleural infections Known non-expandable lung prior to this pleural infection Known or high clinical suspicion of a malignant pleural effusion Existing indwelling or tunneled pleural catheter Current infected hepatic hydrothorax or evidence of another abdominal process (e.g. pancreatic cyst or renal cyst) communicating with the pleural space Active bleeding, or any condition in which bleeding is either a significant risk or would be difficult to manage Fully anticoagulated patients on heparin, warfarin or novel oral anti-coagulants who are not able to temporarily discontinue anti-coagulants while receiving study medication and for 2 days after last dose of study medication Note: patients receiving low-molecular weight heparin for immobilization or anti-platelet agents are not excluded. Presence of severe metabolic derangements that would interfere with study assessments Systolic blood pressure >185 mmHg or diastolic blood pressure > 110 mmHg at screening Hemodynamically unstable and/or requires use of intravenous vasopressor therapy Expected survival < 3 months from a pathology other than the qualifying infected, non-draining pleural effusion (e.g. metastatic lung carcinoma)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 400,000 U LTI-01<br>400,000 U LTI-01 once a day (qd) x 3 days administered intrapleurally | Drug: LTI-01<br>* single-chain urokinase plasminogen activator, scuPA<br>|
| Experimental: 800,000 U LTI-01<br>800,000 U LTI-01 qd x 3 days administered intrapleurally | Drug: LTI-01<br>* single-chain urokinase plasminogen activator, scuPA<br>|
| Experimental: 1,200,000 U LTI-01<br>1,200,000 U LTI-01 qd x 3 days administered intrapleurally | Drug: LTI-01<br>* single-chain urokinase plasminogen activator, scuPA<br>|
| Placebo Comparator: Placebo<br>placebo (normal saline) 6ml qd x 3 days administered intrapleurally | Drug: Placebo<br>* normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of referral to surgery | Treatment failure, as evidenced by continued or worsening pleural sepsis and failure to adequately drain pleural effusion, resulting in referral to surgery | Post treatment (Day 4/Hospital discharge or at time of treatment failure) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change in pleural opacity | Change from baseline in absolute pleural opacity and relative change from baseline in pleural opacity volume assessed by chest CT at Day 4 | Post treatment (Day 4 or at time of treatment failure) |