A Study to Evaluate the Efficacy and Safety of Once Daily Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Arterial Hypertension (PAH)

Официальное название

A Phase 3, Randomized, Double-Blind, Placebo-controlled, Multicenter, Parallel-group Study to Evaluate the Efficacy and Safety of Once Daily Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Arterial Hypertension

Обзор

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

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 6-Minute Walk Distance (6MWD) Measured at 1 to 3 Hours Post-Dose From Baseline at Week 24 [Срок оценки: Baseline, Week 24]

Вторичные конечные точки (11)

• Percentage of Participants With an Improvement From Baseline in World Health Organization (WHO) Functional Class at Week 24 [Срок оценки: Baseline, Week 24]
• Change in 6MWD Measured at 24 Hours (±2) Since the Last Dose From Baseline at Week 22 [Срок оценки: Baseline, Week 22]
• Change From Baseline in the Concentration of N-Terminal Pro Hormone Brain Natriuretic Peptide (NT-proBNP) at Week 24 [Срок оценки: Baseline, Week 24]
• Change From Baseline at Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire (PAH-SYMPACT) Physical Impacts Domain Score [Срок оценки: Baseline, Week 24]
• Change From Baseline at Week 24 in PAH-SYMPACT Cardiopulmonary Symptoms Domain Score [Срок оценки: Baseline, Week 24]
• Time to First Clinical Worsening Event From Baseline Through Week 24 [Срок оценки: Baseline up to Week 24]
• Change in Multiparameter Risk Score From Baseline at the Scheduled Visits Over 24 Weeks (REVEAL Lite 2.0) [Срок оценки: Baseline up to Week 24]
• Changes From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) per Right Ventricular Systolic Pressure (RVSP) at Week 24 [Срок оценки: Baseline, Week 24]
• Change From Baseline at the Scheduled Visits Over 24 Weeks in PAH-SYMPACT Cardiovascular Symptoms Domain Score [Срок оценки: Baseline up to Week 24]
• Changes From Baseline at the Scheduled Visits Over 24 Weeks in PAH-SYMPACT Cognitive/Emotional Impacts Domain Score [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

• Participants must have a diagnosis of World Health Organisation (WHO) Group 1 pulmonary hypertension (PAH) in any of the following subtypes, in accordance with European Society of Cardiology European Respiratory Society (ESC/ERS) Guidelines:

• Idiopathic PAH
• Heritable PAH
• Drug/toxin-induced PAH
• Connective tissue disease (CTD)-associated PAH
• PAH associated with congenital heart disease-related to simple systemic-to-pulmonary shunt at least 1 year following repair.
• PAH diagnosis for at least 3 months prior to Screening.
• New York Heart Association (NYHA) or World Health Organization (WHO) functional class II-IV.
• Participants must be on stable PAH therapy consisting of 1 to 3 medications from the following classes:

• Endothelin receptor antagonists (eg, ambrisentan, bosentan, macitentan) for at least 90 days prior to Screening with the last 30 days on stable dose
• Phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil) for at least 90 days prior to Screening with the last 30 days on stable dose
• Guanylate cyclase stimulator (eg, riociguat) for at least 90 days prior to Screening with the last 30 days on stable dose
• Activin signaling inhibitor (e.g., sotatercept) for at least 6 months prior to Screening, with the last 3 months on stable dose and meeting all the following conditions:

• no active clinically significant bleeding (eg, epistaxis and gingival bleeding requiring medical interventions) within the past 3 months.
• no history of major bleeding events or risks (eg, gastrointestinal or intracranial bleeding) within the past 6 months.
• platelet counts ≥100,000 per microlitre (μL) at Screening
• For both 6-minute walk tests (6MWTs), the values of 6-minute walk distance (6MWD) should be ≥ 150 and ≤ 450 meters at Screening.
• Right heart catheterization (RHC) at Screening (or within 6 months prior to Screening, if available). Prior RHC may be used provided there has been no change in background PAH therapy and doses. The RHC must meet all of the following hemodynamic criteria:

• Mean pulmonary arterial pressure (PAP) >20 millimetre of mercury (mmHg) at rest.
• pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) ≤15 mmHg.
• pulmonary vascular resistance (PVR) of ≥5 wood units (WU).

Критерии исключения

• Diagnosis of PH WHO Groups 2, 3, 4, or 5, or subtypes of PH WHO Group 1 other than described in inclusion criterion 2 (eg, human immunodeficiency virus (HIV), complex congenital heart disease-associated PAH, portal hypertension-associated PAH, pulmonary veno-occlusive disease, Schistosomiasis associated PAH).
• Clinically significant left heart disease, including left-sided valvular disease, left ventricular systolic or diastolic dysfunction, echocardiographic findings suggestive of post-capillary pulmonary hypertension, unstable ischemic heart disease, or unstable arrhythmias.
• Evidence of airflow obstruction defined by forced expiratory volume in 1 second (FEV1) per forced vital capacity (FVC) <0.7.
• Evidence of significant restrictive lung disease as evidenced by FVC <70% predicted normal.
• 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).
• 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

США · 2 центра

• USA008 — Santa Barbara
• USA007 — Anderson

Идентификаторы

NCT: NCT07481981 · INS1009-301 · 2026-525265-48-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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