Open-Label Extension Study of Inhaled Treprostinil Palmitil Powder for Safety and Tolerability in Pulmonary Hypertension Associated with Interstitial Lung Disease

Pulmonary Hypertension Associated with Interstitial Lung Disease is the target condition. The primary objective is to assess the safety and tolerability of long‑term administration of treprostinil palmitil inhalation powder in participants previously enrolled in Study INS1009‑311, providing critical data on adverse‑event profile and treatment sustainability for chronic therapy. Secondary objectives include evaluation of the long‑term impact of the investigational product on: - exercise capacity; - pulmonary function; - blood biomarkers of disease severity; - frequency of ILD exacerbations; - rate of clinical worsening; - patient‑reported disease‑related symptoms and associated physical activities; - health‑related quality of life; - major morbidity and mortality.

Approximately 110 individuals enrolled in the trial; both female and male participants were included. All subjects had Pulmonary Hypertension Associated with Interstitial Lung Disease and had previously completed the lead‑in PH‑ILD TPIP Study INS1009‑311. Participants were required to be capable of providing signed informed consent and to agree not to partake in other interventional studies or use investigational products during the study period. The cohort comprised patients rather than healthy volunteers, and vulnerable persons were not excluded. Specific age ranges were not disclosed in the provided information. General health status was limited to the target disease condition, with no additional lifestyle criteria reported.

The study is a long‑term, open‑label extension evaluating the safety and tolerability of Treprostinil Palmitil Inhalation Powder in participants with Pulmonary Hypertension Associated with Interstitial Lung Disease who have completed the preceding lead‑in trial. After a screening visit to verify completion of the prior study and obtain informed consent, participants enter a baseline visit (pre‑OLE) at which demographic data, vital signs, laboratory tests, 12‑lead ECG, supplemental‑oxygen use, and baseline functional assessments (6‑minute walk distance, spirometry, NT‑proBNP, and patient‑reported outcomes) are recorded. Subsequent study visits occur at regular intervals (e.g., every 12 weeks) for up to 104 weeks, during which adverse events, laboratory parameters, vital signs, physical examination, ECG, oxygen requirement, and efficacy measures are reassessed. The final end‑of‑study visit is scheduled at week 104 or at early discontinuation. Participants remain in the trial for a maximum of two years; early termination may occur because of serious adverse events, disease progression meeting predefined clinical‑worsening criteria, need for lung transplantation, death, withdrawal of consent, or non‑compliance with protocol requirements. The overall trial enrolment period is projected from September 2026 to April 2031.

The investigational product is Treprostinil palmitil inhalation powder supplied in a dry‑powder formulation for inhalation use. Each dose contains 1280 µg of the active substance and is administered via a designated inhalation device. The powder is delivered as a single inhalation per dosing interval, with the schedule defined by the study protocol.

The comparator is a placebo inhalation powder capsule that matches the investigational product in appearance and device compatibility. The placebo capsules are available in four strength levels containing 80 µg, 160 µg, 320 µg, or 640 µg of the inactive formulation, but contain no active treprostinil palmitil. Administration follows the same inhalation procedure as the active product.

Dosing is recorded in the study log at each visit, and adherence is monitored through device dose counters and participant diaries. Participants are instructed to use the inhalation device exactly as directed and to report any missed or additional doses. Compliance data are reviewed periodically to ensure protocol‑defined dosing intervals are maintained.

Efficacy will be evaluated using a series of secondary endpoints that reflect functional capacity, pulmonary function, biomarker levels, disease exacerbations, clinical worsening, patient‑reported outcomes, and overall morbidity and mortality. Key parameters include the change in 6MWD measured post‑dose from the pre‑extension baseline to week 104, absolute and percent changes in forced vital capacity (FVC), FVC% predicted, forced expiratory volume in one second (FEV1) and FEV1% predicted, and the change in plasma N‑terminal pro‑brain natriuretic peptide (NT‑proBNP) concentration over the same period. Additional efficacy measures comprise the annualized rate of interstitial lung disease (ILD) exacerbations, the proportion of participants experiencing a clinical worsening event (defined by hospitalization for cardiopulmonary indications, ≥15 % decline in 6MWD confirmed by repeat testing, signs of right‑heart failure or WHO/NYHA class deterioration, lung transplantation, or death), mean changes in the Lung‑Patient‑Reported Outcomes (L‑PF) total symptom domain score and its cough, dyspnea, and impact subdomains, mean changes in the EQ‑5D‑5L index and visual analogue scale scores, and the proportion of participants with a major morbidity or mortality event (hospitalization, lung transplantation, or death).

Assessments will be performed at the pre‑extension baseline and at scheduled visits throughout the 104‑week open‑label extension. Functional capacity will be measured using the standardized six‑minute walk test, while pulmonary function will be evaluated with spirometry to obtain FVC and FEV1 values. NT‑proBNP concentrations will be quantified through validated laboratory assays. ILD exacerbations and clinical worsening events will be recorded continuously and adjudicated according to predefined criteria. Patient‑reported outcomes will be collected using the L‑PF questionnaire and the EQ‑5D‑5L instrument. All data will be analyzed as change from baseline, with longitudinal statistical methods applied to assess trends over the study duration.