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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (8)

• Time From Randomization to First Clinical Worsening Over the 24-Week Treatment Period [Срок оценки: Up to Week 24]
• Time From Randomization to First Major Morbidity or Mortality Event Over the 24-Week Treatment Period [Срок оценки: Up to Week 24]
• Change From Baseline in N-Terminal Pro Hormone Brain Natriuretic Peptide (NT-proBNP) Plasma Concentration Over 24 Weeks [Срок оценки: 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 [Срок оценки: At Week 24]
• Change in 6MWD Measured at Trough Exposure From Baseline to Week 22 [Срок оценки: Baseline, Week 22]
• Change From Baseline in 6MWD Measured at Peak Exposure Over 20 Weeks [Срок оценки: Baseline up to Week 20]
• Mean Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Total Symptom Domain Score Over 24 Weeks [Срок оценки: Baseline up to Week 24]
• Plasma Concentrations of Treprostinil Palmitil (TP) and Treprostinil (TRE) [Срок оценки: Pre-dose and post-dose at multiple timepoints up to Week 24]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Япония · 14 центров

• JPN006 — Nagakute
• JPN011 — Hirosaki
• JPN002 — Narashino-shi
• JPN004 — Narita-shi
• JPN001 — Sapporo
• JPN007 — Yokohama
• JPN010 — Kyotoshi
• JPN005 — Nagano
• … и ещё 6 центров

Испания · 11 центров

Список центров уточняется — проверьте первичный протокол.

Франция · 10 центров

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

США · 8 центров

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

Германия · 8 центров

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

South Korea · 6 центров

Список центров уточняется — проверьте первичный протокол.

Аргентина · 5 центров

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

Израиль · 5 центров

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

Италия · 5 центров

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

Малайзия · 5 центров

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

Тайвань · 5 центров

Список центров уточняется — проверьте первичный протокол.

Австралия · 4 центра

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

Грузия · 4 центра

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

Великобритания · 4 центра

Список центров уточняется — проверьте первичный протокол.

Бельгия · 2 центра

• BEL002 — Leuven
• BEL001 — Anderlecht

Греция · 2 центра

• GRC003 — Pátrai
• GRC002 — Athens

Новая Зеландия · 2 центра

• NZL001 — Christchurch
• NZL002 — Dunedin

Португалия · 2 центра

• PRT002 — Almada
• PRT001 — Lisbon

Румыния · 2 центра

• ROU002 — Târgu Mureş
• … и ещё 1 центр

Швейцария · 2 центра

Список центров уточняется — проверьте первичный протокол.

Австрия · 1 центр

• AUT002 — Innsbruck

Чехия · 1 центр

• CZE001 — Prague

Дания · 1 центр

• DNK001 — Aarhus N

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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