A Study to Evaluate the Safety and Tolerability of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease

A Phase 2, Randomized, Double-Blind, Multicenter, Placebo-Controlled Study to Evaluate the Safety and Tolerability of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease

The primary objective of this study is to evaluate the safety and tolerability of treprostinil palmitil inhalation powder (TPIP) compared with placebo

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Treprostinil Palmitil

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Insmed Medical Information; Phone Number: 1-844-446-7633; Email: medicalinformation@insmed.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, CI094AAD
    • ARG008
  • Ciudad Autónoma De BuenosAires
    • Barracas, Ciudad Autónoma De BuenosAires, Argentina, C1280AEB
      • ARG003
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2013KDS
      • ARG001
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • AUS003
    • Macquarie Park, New South Wales, Australia, 2109
      • AUS005
• Belgium
  • Liège, Belgium, 4000
    • BEL002
• Germany
  • Berlin, Germany, 13125
    • GER002
  • Berlin, Germany, 14050
    • GER012
  • Munich, Germany, 81377
    • GER004
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69126
      • GER006
  • Hessen
    • Gießen, Hessen, Germany, 35392
      • GER010
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45239
      • GER003
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • GER001
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • ITA003
  • Lombardia
    • Milano, Lombardia, Italy, 20123
      • ITA004
    • Monza, Lombardia, Italy, 20900
      • ITA002
  • Sicilia
    • Palermo, Sicilia, Italy, 90127
      • ITA001
• Spain
  • Barcelona, Spain, 08035
    • ESP010
  • Barcelona, Spain, 08907
    • ESP005
  • Santiago de Compostela, Spain, 15706
    • ESP009
  • las Palmas de Gran Canaria, Spain, 35010
    • ESP006
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • ESP007
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07120
      • ESP003
• United Kingdom
  • Lanarkshire
    • Glasgow, Lanarkshire, United Kingdom, G81 4HX
      • GBR003
  • Yorkshire
    • Sheffield, Yorkshire, United Kingdom, S10 2JF
      • GBR001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males and females must be ≥ 18 to ≤ 80 years of age at the time of signing the informed consent form (ICF).
• Diagnosis of pulmonary hypertension (PH) associated with interstitial lung disease (ILD) (including idiopathic interstitial pneumonia [IIP], idiopathic pulmonary fibrosis [IPF], connective tissue disease [CTD], sarcoidosis).
• Male and female participants must use contraceptives that are consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male participants:

Male participants who are not sterile, with female partners of childbearing potential, must be using effective contraception from Day 1 to at least 90 days after the last dose of study drug.

Male participants with women of child bearing potential (WOCBP) partner must use a condom in order to avoid potential exposure to embryo/fetus.

- Female participants: Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, (ie,hysterectomy and/or bilateral salpingo-oophorectomy) or using highly effective contraception methods (ie, methods that alone or in combination achieve <1% unintended pregnancy rates per year when used consistently and correctly) from Day 1 to at least 90 days after the last dose of study drug.

- Capable of giving signed informed consent that includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria:

• Primary diagnosis of chronic obstructive pulmonary disease (COPD).
• Allergy, or documented hypersensitivity or contraindication to TPIP or treprostinil (TRE) or mannitol (an excipient of the TPIP formulation).
• Received or currently treated with riociguat, endothelin receptor antagonists, selexipag, phosphodiesterase 5 (PDE5) inhibitors and/or prostacyclin analogues within 30 days prior to Screening.
• Started therapy with pirfenidone or nintedanib < 90 days prior to Screening, OR, if already receiving either medication, there is a dose change within 30 days of Screening Visit.
• Any known ventricular or supraventricular tachyarrhythmia (except for paroxysmal atrial fibrillation), and/or any symptomatic bradycardia.
• History of heart disease including left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant valvular, constrictive, or symptomatic atherosclerotic heart disease (eg, stable angina, myocardial infarction, etc).
• Participation in a cardiopulmonary rehabilitation program within 30 days of the first Screening Visit. Participation in the maintenance program of a cardiopulmonary rehabilitation program is allowed.
• Acutely decompensated heart failure within 30 days of Screening Visit.
• Active and current symptomatic coronavirus disease 2019 (COVID-19) and/or previous diagnosis of moderate to severe disease, or hospitalization due to COVID-19.
• Supplemental oxygen requirement > 10L/min at rest at Screening.
• Exacerbation of underlying lung disease or active pulmonary or upper respiratory infection within 30 days of the first dose of study drug (may be rescreened at appropriate time).
• Current or recent (past 30 days) lower respiratory tract infection (may be rescreened at appropriate time).
• Any form of congenital heart disease or congenital heart defect (repaired or unrepaired) other than a patent foramen ovale.
• History of alcohol or drug abuse within 6 months prior to Screening.
• Current use of cigarettes (as defined by Center for Disease Control (CDC)) 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.
• Participants who currently inhale marijuana (recreational or medical).
• Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements, in particular with 6-minute walk test (6MWT) (eg, angina pectoris, claudication, musculoskeletal disorder, need for walking aids).

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; Participants will be administered TPIP once per day at a starting dose of 80 micrograms (μg). Participants will be titrated up to the highest tolerated dose for each individual participant of between 80 μg and 640 μg during the initial 3 weeks of treatment. The overall treatment period will be 16 weeks.	Drug: Treprostinil Palmitil; Oral inhalation using a capsule-based dry powder inhaler device.; Other Names: INS1009
Placebo Comparator: Placebo; Participants will be administered a placebo matching TPIP once daily.	Drug: Placebo; Oral inhalation using a capsule-based dry powder inhaler device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Who Experience Any Number of Treatment Emergent Adverse Events (TEAEs)	Up to Day 140
Number of Participants Who Experience Any Number of Serious Adverse Events (SAEs)	Up to Day 140
Change from Baseline in Saturation of Peripheral Capillary Oxygenation (SpO2) Levels	Pre-, during, and post- 6-minute walk test (6MWT) at Baseline, Week 5, Week 10, and Week 16

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax) of Treprostinil Palmitil	Day 1 to Week 16
Cmax of Treprostinil	Day 1 to Week 16
Time to Maximum Plasma Concentration (Tmax) of Treprostinil Palmitil	Day 1 to Week 16
Tmax of Treprostinil	Day 1 to Week 16
Area Under Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUCtau) of Treprostinil Palmitil	Day 1 to Week 16
AUCtau of Treprostinil	Day 1 to Week 16
Area Under Concentration-time Curve From 0 to Infinity (AUC∞) of Treprostinil Palmitil	Day 1 to Week 16
AUC∞ of Treprostinil	Day 1 to Week 16
Area Under Concentration-time Curve From Time 0 to Last Measurable Concentration (AUClast) of Treprostinil Palmitil	Day 1 to Week 16
AUClast of Treprostinil	Day 1 to Week 16
Apparent Total Clearance (CL/F) of Treprostinil Palmitil	Day 1 to Week 16
CL/F of Treprostinil	Day 1 to Week 16
Elimination Half-life (t1/2) of Treprostinil Palmitil	Day 1 to Week 16
t1/2 of Treprostinil	Day 1 to Week 16
Apparent Volume of Distribution After Terminal Phase (Vd/F) of Treprostinil Palmitil	Day 1 to Week 16
Vd/F of Treprostinil	Day 1 to Week 16

Collaborators and Investigators

• Sponsor: Insmed Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2022
• Primary Completion (Actual): March 14, 2024
• Study Completion (Actual): March 14, 2024

Study Registration Dates

• First Submitted: December 10, 2021
• First Submitted That Met QC Criteria: January 3, 2022
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Interstitial Lung Disease; Treprostinil Palmitil
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Hypertension; Lung Diseases; Hypertension, Pulmonary; Lung Diseases, Interstitial; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: INS1009-211; 2021-003294-66 (EudraCT Number)

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