Efficacy and Safety Study of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)

Official title

A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group Study to Evaluate the Efficacy and Safety of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease

Overview

The primary objective of this study is to evaluate the effect of 24-weeks of once daily treatment with TPIP versus placebo on exercise capacity in adults with PH-ILD.

Interventions

• Drug Treprostinil Palmitil Inhalation Powder
  Oral inhalation using a capsule-based dry powder inhaler device.
• Drug Placebo
  Oral inhalation using a capsule-based dry powder inhaler device.

Primary outcome measures

• Change in 6MWD Measured at Peak Exposure From Baseline to Week 24 [Time frame: Baseline, Week 24]

Secondary outcome measures (8)

• Time From Randomization to First Clinical Worsening Over the 24-Week Treatment Period [Time frame: Up to Week 24]
• Time From Randomization to First Major Morbidity or Mortality Event Over the 24-Week Treatment Period [Time frame: Up to Week 24]
• Change From Baseline in N-Terminal Pro Hormone Brain Natriuretic Peptide (NT-proBNP) Plasma Concentration Over 24 Weeks [Time frame: Baseline up to Week 24]
• Number of Participants With Greater Than or Equal to (>=) 30% Decrease in NT-proBNP or Who Maintained/Achieved Less Than (<) 300 Nanogram per Liter (ng/L) of NT-proBNP Level at Week 24 [Time frame: At Week 24]
• Change in 6MWD Measured at Trough Exposure From Baseline to Week 22 [Time frame: Baseline, Week 22]
• Change From Baseline in 6MWD Measured at Peak Exposure Over 20 Weeks [Time frame: Baseline up to Week 20]
• Mean Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Total Symptom Domain Score Over 24 Weeks [Time frame: Baseline up to Week 24]
• Plasma Concentrations of Treprostinil Palmitil (TP) and Treprostinil (TRE) [Time frame: Pre-dose and post-dose at multiple timepoints up to Week 24]

Eligibility criteria

Inclusion criteria

• Diagnosis of PH World Health Organisation (WHO) Group 3 associated with ILD \[including but not limited to idiopathic interstitial pneumonia (IIP), chronic hypersensitivity pneumonitis (HSP), connective tissue disease-associated interstitial lung disease (CTD-ILD), combined pulmonary fibrosis and emphysema (CPFE)\].
• Confirmation of fibrotic interstitial lung disease by centrally overread computed tomography (CT) scan performed at Screening or within prior 12 months.
• PH confirmed by right heart catheterization (RHC) at Screening or within 12 months prior to Screening, with the following hemodynamic findings:

• Mean pulmonary arterial pressure (mPAP) >20 millimetre of mercury (mmHg) and
• Pulmonary capillary wedge pressure (PCWP) of ≤15 mmHg and
• Pulmonary vascular resistance (PVR) ≥4 wood units (WU).
• 6 Minute walking distance (6MWD) ≥100 and ≤500 meters at two 6MWTs at Screening performed at least 4 hours apart, with the difference between the 2 distances ≤15%.
• Participants receiving chronic medication for underlying disease (e.g., antifibrotic, immunomodulators, immunosuppressants, etc.) and/or phosphodiesterase 5 (PDE5) inhibitors, should be on this treatment for ≥90 days and on a stable dose for ≥30 days prior to Screening.
• Capable of giving signed informed consent as described in Section 10.1.5 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria

• Diagnosis of Pulmonary Hypertension WHO Groups 1, 2, 4, or 5, or subtypes of PH WHO Group 3 other than interstitial lung disease.
• Primary diagnosis of chronic obstructive pulmonary disease (COPD) and/or forced expiratory volume in 1 second (FEV1)/FVC <0.7 (based on screening or historical spirometry within the prior 6 months).
• Clinically significant left heart disease:

• evidence of clinically significant left-sided valvular heart disease,
• left ventricular failure with left ventricular ejection fraction (LVEF) <45%, or diagnosis of heart failure with preserved ejection fraction (HFpEF)
• echocardiography findings at Screening suggestive for postcapillary PH
• unstable ischemic heart disease
• unstable arrhythmia, including uncontrolled atrial fibrillation (rate-controlled arrhythmia or paroxysmal atrial fibrillation is allowed)
• Evidence of chronic thromboembolic disease or recent (within 6 months of Screening) acute pulmonary embolism.
• Known hypersensitivity or contraindication to treprostinil or TPIP or TPIP formulation excipients (e.g., mannitol, leucine).
• Current use of cigarettes or e-cigarettes: An adult who has smoked at least 100 cigarettes in his or her lifetime and who currently smokes either every day or some days.
• Current use of inhaled marijuana, recreational or medical (current use defined as used at least one or more times during the past 30 days prior to Screening) or expected use during the study.
• Any other medical or psychological condition including relevant laboratory abnormalities at Screening that, in the opinion of the Investigator, suggest a new and/or insufficiently understood disease and/or may present an unreasonable risk to the study participant as a result of his/her participation in this clinical trial, may impede their ability complete the study or the study assessments or confound the outcomes of the trial.

Note: Other protocol defined inclusion/exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Japan · 14 centers

• JPN006 — Nagakute
• JPN011 — Hirosaki
• JPN002 — Narashino-shi
• JPN004 — Narita-shi
• JPN001 — Sapporo
• JPN007 — Yokohama
• JPN010 — Kyotoshi
• JPN005 — Nagano
• … and 6 more centers

Spain · 11 centers

Center list to be confirmed — check the primary protocol.

France · 10 centers

• FRA009 — Nice
• FRA002 — Marseille
• FRA004 — Angers
• FRA007 — Lille
• FRA008 — Saint Priest En Jarez
• FRA003 — Le Kremlin-Bicêtre
• FRA001 — Poitiers
• FRA010 — Brest
• … and 2 more centers

United States · 8 centers

• USA010 — Los Angeles
• USA001 — Santa Barbara
• USA006 — Naples
• USA026 — St. Petersburg
• USA002 — Kansas City
• USA003 — Bend
• USA013 — Philadelphia
• USA008 — Richmond

Germany · 8 centers

• DEU005 — Immenhausen
• DEU012 — Stuttgart
• DEU003 — München
• DEU006 — München
• DEU008 — Bonn
• DEU009 — Homburg
• DEU011 — Lübeck
• DEU010 — Gauting

South Korea · 6 centers

Center list to be confirmed — check the primary protocol.

Argentina · 5 centers

• ARG002 — CiudadAutonoma de Buenos Aires
• ARG003 — Río Cuarto
• ARG008 — San Miguel de Tucumán
• ARG004 — Córdoba
• ARG001 — Córdoba

Israel · 5 centers

• ISR003 — Petah Tikva
• ISR002 — Jerusalem
• ISR005 — Haifa
• ISR001 — Haifa
• ISR004 — Tel Aviv

Italy · 5 centers

• ITA011 — Bologna
• ITA008 — Milan
• ITA001 — Pavia
• ITA003 — Roma
• ITA012 — Sassari

Malaysia · 5 centers

• MYS004 — Alor Star
• MYS001 — Kota Bharu
• MYS003 — Kuantan
• MYS002 — Kuching
• MYS005 — Kajang

Taiwan · 5 centers

Center list to be confirmed — check the primary protocol.

Australia · 4 centers

• AUS001 — Camperdown
• AUS006 — Kingswood
• AUS005 — New Lambton Heights
• AUS003 — Westmead

Georgia · 4 centers

• GEO002 — Tbilisi
• GEO004 — Tbilisi
• GEO003 — Tbilisi
• GEO001 — Tbilisi

United Kingdom · 4 centers

Center list to be confirmed — check the primary protocol.

Belgium · 2 centers

• BEL002 — Leuven
• BEL001 — Anderlecht

Greece · 2 centers

• GRC003 — Pátrai
• GRC002 — Athens

New Zealand · 2 centers

• NZL001 — Christchurch
• NZL002 — Dunedin

Portugal · 2 centers

• PRT002 — Almada
• PRT001 — Lisbon

Romania · 2 centers

• ROU002 — Târgu Mureş
• … and 1 more center

Switzerland · 2 centers

Center list to be confirmed — check the primary protocol.

Austria · 1 center

• AUT002 — Innsbruck

Czechia · 1 center

• CZE001 — Prague

Denmark · 1 center

• DNK001 — Aarhus N

Identifiers

NCT: NCT07179380 · INS1009-311 · 2025-521558-40-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗