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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Treprostinil Palmitil Inhalation Powder

• Study Type: Interventional
• Enrollment (Estimated): 344
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Insmed Medical Information; Phone Number: 18444467633; Email: medicalinformation@insmed.com

Study Locations

• United States
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Recruiting
      • USA007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treprostinil Palmitil Inhalation Powder; Participants will receive TPIP, once daily (QD), at a starting dose of 80 micrograms (μg) up to maximum tolerated dose (up to 1280 μg) for 24 weeks.	Drug: Treprostinil Palmitil Inhalation Powder; Oral inhalation using a capsule-based dry powder inhaler device.; Other Names: INS1009
Placebo Comparator: Placebo; Participants will receive a TPIP-matching placebo, QD, for 24 weeks.	Drug: Placebo; Oral inhalation using a capsule-based dry powder inhaler device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in 6-Minute Walk Distance (6MWD) Measured at 1 to 3 Hours Post-Dose From Baseline at Week 24	Baseline, Week 24

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Insmed Incorporated

Study record dates

Study Major Dates

• Study Start (Estimated): June 26, 2026
• Primary Completion (Estimated): December 28, 2028
• Study Completion (Estimated): January 28, 2029

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pulmonary Arterial Hypertension
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension
• Other Study ID Numbers: INS1009-301; 2026-525265-48-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No