A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group Study to Evaluate the Efficacy and Safety of Trepostinil Palmitil Inhalation Powder in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Insmed Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

12 Feb 2026 → ongoing

Decision date (initial)

2026-01-26

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Insmed Incorporated

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Efficacy, Safety

To evaluate the effect of TPIP compared with placebo on exercise capacity

Secondary objectives 7

1. To evaluate the effect of TPIP compared with placebo on clinical worsening
2. To evaluate the effect of TPIP compared with placebo on major morbidity and mortality
3. To evaluate the effect of TPIP compared with placebo on NT-proBNP levels
4. To evaluate the effect of TPIP compared with placebo on trough exercise capacity
5. To evaluate the effect of TPIP compared with placebo on exercise capacity
6. To evaluate the effect of TPIP compared with placebo on overall symptoms and associated physical activities
7. To evaluate the PK of TP and TRE in plasma

Conditions and MedDRA coding

Pulmonary Hypertension Associated with Interstitial Lung Disease

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Males and females ≥18 years of age at the time of signing the ICF. 2. Diagnosis of PH WHO Group 3 associated with ILD (including but not limited to IIP, chronic HSP, CTD-ILD, CPFE) 3. Confirmation of fibrotic ILD by centrally overread CT scan performed at Screening or within prior 12 months. 4. PH confirmed by RHC at Screening or within 12 months prior to Screening, with the following hemodynamic findings: a. mPAP >20 mmHg and b. PCWP of ≤15 mmHg and c. PVR ≥4 Wood Units 5 6MWD ≥100 and ≤500 meters at two 6MWTs at S two distances at Screening perfored at least 4 hours apart, with the difference between the 2 distances ≤15% 7. Participants receiving chronic medication for underlying disease (eg, antifibrotic, immunomodulators, immunosuppressants, etc) and/or PDE5 inhibitors, should be on this treatment for ≥90 days and on a stable dose for ≥30 days prior to Screening. 8. Male and female (WOCBP) participants must use contraceptives that are consistent with local regulations regarding the methods of contraception for those participating in clinical studies 9. Capable of giving signed informed consent as described in Section 10.1.5 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion criteria 6

1. • Diagnosis of PH WHO Groups 1, 2, 4, or 5, or subtypes of PH WHO Group 3 other than Interstitial lung disease as described in Inclusion criterion 2 • Primary diagnosis of COPD and/or FEV1/FVC <0.7 (based on screening or historical spirometry within the prior 6 months)
2. • Clinically significant left heart disease: • evidence of clinically significant left-sided valvular heart disease, • left ventricular failure with LVEF <45%, or diagnosis of 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). • Acutely decompensated heart failure within 30 days of Screening or during Screening. • QTcF interval >500 ms at Screening or Baseline, or known medical history of long QT syndrome. • Evidence of chronic thromboembolic disease or recent (within 6 months of Screening) acute pulmonary embolism.
3. •Platelet count <50.0 x 103/μL at Screening, and/or unexplained coagulation abnormalities in repeated laboratory tests during the screening. •Systolic BP <90 mmHg at Screening and Baseline. •Supplemental oxygen requirement at rest >10 L/min at Screening (otherwise use of supplemental oxygen is allowed). •Active cardiopulmonary rehabilitation program started within 30 days of Screening and planned to continue or be initiated during the study. •Known hypersensitivity or contraindication to treprostinil or TPIP or TPIP formulation excipients (eg, mannitol, leucine). •Exacerbation of underlying lung disease or active respiratory tract infection within 30 days of Screening or during Screening (based on the last dose of therapy or hospitalization, whichever is later).
4. •Any acute or chronic musculoskeletal disease, injury, or other condition (eg, arthritis affecting the lower limbs, recent hip or knee joint replacement), other than the disease under study that, in the opinion of the Investigator, might affect the participant’s ability to perform the 6MWT and/or the 6MWT accuracy. •Active liver disease or hepatic dysfunction: • Elevated serum ALT or AST levels >3 × ULN or total bilirubin >1.5 × ULN (except when explained by Gilbert's syndrome) at Screening • Moderate to severe chronic hepatic impairment (Child-Pugh Class B-C) • Hepatitis B and/or hepatitis C with evidence of recent infection and/or active virus replication (participant with undetectable hepatitis B virus DNA and negative hepatitis C virus RNA are acceptable)
5. •History of HIV infection or positive serology for HIV-1 or HIV-2. •Severe concomitant illness (other than the disease under study) limiting life expectancy (<6 months). •History of solid organ transplantation, or expected transplant within 24 weeks after randomization(otherwise participant on lung transplant list are accepted). •Any physical limitation that would impair the participant's use of the inhaler device. •Use of any investigational drug/device, or participation in any investigational study within 30 days prior to Screening. •History of alcohol or drug abuse, as judged by the Investigator, within 6 months prior to Screening. •Current use of cigarettes (as defined by 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 (Glossary, CDC Tobacco Glossary, 2017).
6. •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. •History of malignancy within 5 years prior to Screening Visit, with exception of completely treated in situ carcinoma of the cervix, in situ melanoma, and completely treated non-metastatic squamous or basal cell carcinoma of the skin. •Pregnant or breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in 6MWD measured at peak exposure from Baseline to Week 24

Secondary endpoints 9

1. Time from randomization to first clinical worsening over 24 weeks
2. Time from randomization to first major morbidity or mortality event over 24 weeks
3. Change in NT proBNP plasma concentration from Baseline over 24 weeks
4. Proportion of participants with improvement in NT proBNP levels over 24 weeks
5. Change in 6MWD measured at trough exposure from Baseline to Week 22
6. Change in 6MWD measured at peak exposure from Baseline over 20 weeks
7. Change in L-PF total symptom domain score from Baseline over 24 weeks
8. Mean Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Total Symptom Domain Score Over 24 Week
9. Plasma Concentrations of Treprostinil Palmitil (TP) and Treprostinil (TRE)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Insmed Inc.

Sponsor organisation

Insmed Inc.

Address

700 Us Highway 202/206

City

Bridgewater

Postcode

08807-1704

Country

United States

Scientific contact point

Organisation

Insmed Inc.

Contact name

Natasha Makulova

Public contact point

Organisation

Insmed Inc.

Contact name

Medical Information

Third parties 21

Locations

12 EU/EEA countries · 73 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 122 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications