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

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

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.

Study Overview

• Status: Completed
• Conditions: Pleural Effusion
• Intervention / Treatment: Drug: Placebo; Drug: LTI-01

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • The University of Alabama at Birmingham
  • California
    • La Jolla, California, United States, 92037
      • UC San Diego Health Jacobs Medical Center
    • Los Angeles, California, United States, 90095
      • University of California (UCLA)
    • Sacramento, California, United States, 95816
      • UC Davis Medical Group
  • Colorado
    • Aurora, Colorado, United States, 80445
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Health System
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • CHI CUMC Bergan Mercy
  • New York
    • Queens, New York, United States, 11040
      • North Shore - Long Island Jewish Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina At Chapel Hill
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • The Pennsylvania State University
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Lung Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2020
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): July 28, 2022

Study Registration Dates

• First Submitted: November 4, 2019
• First Submitted That Met QC Criteria: November 8, 2019
• First Posted (Actual): November 12, 2019

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 24, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Pleural Diseases; Pleural Effusion
• Other Study ID Numbers: LTI-01-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No