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NCT07481981PHASE3Recruiting

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

Insmed Incorporated

Start Date

7/21/2026

Completion Date

1/28/2029

Summary

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.

Eligibility Criteria

Age Range: 18 years to 75 years

Inclusion Criteria * 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). Exclusion Criteria * 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.

Interventions

DRUG

Treprostinil Palmitil Inhalation Powder

DRUG

Placebo

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Conditions

Pulmonary Arterial Hypertension

Locations

USA012

Los Angeles, California 90027

United States

USA008

Santa Barbara, California 93105

United States

USA005

Torrance, California 90502

United States

USA010

Kansas City, Kansas 66160

United States

USA028

Omaha, Nebraska 68198-6450

United States

USA022

New Hyde Park, New York 11042

United States

USA011

New York, New York 10016

United States

USA015

New York, New York 10075

United States

USA013

Rochester, New York 14642

United States

USA006

Philadelphia, Pennsylvania 19140

United States

USA007

Anderson, South Carolina 29621

United States

ARG001

Buenos Aires, Buenos Aires F.D. C1425AIN

Argentina

ARG004

Río Cuarto, Córdoba Province X5080AEV

Argentina

ARG005

San Miguel de Tucumán, Tucumán Province T4000AXL

Argentina

AUS002

Camperdown, New South Wales 2050

Australia

AUS003

Westmead, New South Wales 2145

Australia

ISR002

Haifa, 3436212

Israel

ISR001

Jerusalem, 9112001

Israel

ISR004

Petah Tikva, 4941492

Israel

ISR005

Ramat Gan, 5265601

Israel

ISR003

Tel Aviv, 6423906

Israel

JPN016

Chiba, Chiba 260-8677

Japan

JPN011

Narashino, Chiba 275-8580

Japan

JPN015

Yahatanishi-ku, Kita Kyushu-shi, Fukuoka 807-8556

Japan

JPN007

Sapporo, Hokkaido 060-8543

Japan

JPN002

Sapporo, Hokkaido 060-8648

Japan

JPN014

Kobe, Hyōgo 650-0017

Japan

JPN003

Okayama, Okayama-ken 701-1192

Japan

JPN017

Minato-ku, Tokyo 108-8329

Japan

JPN004

Mitaka-shi, Tokyo 181-8611

Japan

NZL001

Auckland, 2025

New Zealand

NZL003

Dunedin, 9016

New Zealand

NZL002

Hamilton, 3240

New Zealand

KOR006

Busan, 49241

South Korea

KOR003

Incheon, 21565

South Korea

KOR002

Seoul, 03080

South Korea

KOR005

Seoul, 03722

South Korea

KOR001

Seoul, 06351

South Korea

TWN002

Taipei, 10449

Taiwan