Efficacy and Safety of Inhaled Treprostinil Liposome in Patients with Pulmonary Hypertension Associated with Interstitial Lung Disease (WHO Group 3)

The primary objective of this study is to evaluate the effect of inhaled treprostinil liposome on the change in walking distance as measured by the six-minute walk test in participants with pulmonary hypertension associated with interstitial lung disease. This assessment is clinically relevant for evaluating functional exercise capacity in this patient population. Secondary objectives include:

• Evaluation of the effect of inhaled treprostinil liposome on time to clinical worsening.
• Assessment of the effect on the six-minute walk distance at Week 16 and Week 24.

The study involves a total of 222 patients diagnosed with pulmonary hypertension associated with interstitial lung disease (WHO Group 3). The participant population includes both males and females within an age range of 18 to 80 years. Inclusion requires a confirmed diagnosis of interstitial lung disease via high resolution computed tomography and hemodynamic evidence of pulmonary hypertension established through right heart catheterization. Specific hemodynamic requirements include a mean pulmonary artery pressure of ≥ 25 mmHg, a pulmonary vascular resistance of ≥ 320 dynes.sec/cm5, and a pulmonary capillary wedge pressure or left-ventricular end-diastolic pressure of ≤ 15 mmHg. Additionally, participants must demonstrate an FEV1/FVC ratio greater than 0.70 and a six-minute walk distance of at least 150 meters.

This Phase 3, multicenter, randomized, double-blind, placebo-controlled study is designed to evaluate the safety and efficacy of treprostinil liposome inhalation suspension in participants with pulmonary hypertension associated with interstitial lung disease. The primary objective is to assess the change from baseline to week 16 in the six-minute walk distance. Secondary endpoints include the time to the first occurrence of a clinical worsening event, such as death, hospitalization for cardio-pulmonary indications, lung transplant, or a specific decrease in walking distance, as well as changes in walking distance at week 24. The study involves a screening process to confirm diagnoses via high resolution computed tomography and right heart catheterization to verify specific hemodynamic parameters. Participants will undergo scheduled assessments to monitor clinical outcomes and safety throughout the trial duration. The estimated study period extends from May 2026 to December 2031.

The experimental treatment consists of treprostinil administered as treprostinil liposome. The medication is provided in the form of an inhalation powder or an inhalation solution. The dosage is 950 µg via the inhalation route.

The control group receives L606 placebo inhalation suspension.

The efficacy of L606 is assessed via the primary endpoint of change from baseline to week 16 in the six-minute walk distance (6MWD). This measurement is obtained through the six-minute walk test (6MWT).

Secondary endpoints include:

• The change from baseline to week 24 in 6MWD.
• The time to the first occurrence of a clinical worsening event (CWE), defined by the following criteria:
  • Death from any cause.
  • Hospitalization for a cardio-pulmonary indication related to the underlying disease.
  • Lung transplant.
  • A decrease in 6MWD greater than 15% from baseline related to pulmonary hypertension associated with interstitial lung disease at two consecutive visits, occurring at least one week apart.