A Phase 3 Trial of Inhaled Mosliciguat in PH-ILD (PHrontier)

A Phase 3, Multicenter, Randomized, Double-Blind Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Inhaled Mosliciguat in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease

A Phase 3, Multicenter, Randomized, Double-Blind Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Inhaled Mosliciguat in Participants with Pulmonary Hypertension Associated with Interstitial Lung Disease

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Vascular Diseases; Fibrosis; Pulmonary Hypertension; Interstitial Lung Disease
• Intervention / Treatment: Drug: Mosliciguat; Device: Dry Powder Inhaler; Drug: Placebo

Detailed Description

This study is a randomized double-blind placebo control study with an extension.

The study consists of 2 periods: a blinded placebo-controlled period (24 weeks) and an extension (beyond 24 weeks).

Participants will be randomized to receive mosliciguat or placebo in the 24-week double-blind treatment period.

All participants who complete the 24-week double-blind period may continue to participate in the extension period where all participants receive mosliciguat.

• Study Type: Interventional
• Enrollment (Estimated): 376
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Pulmovant Inc; Phone Number: +1-919-462-1310; Email: clinicaltrials@pulmovant.com

Study Locations

• United States
  • Florida
    • Kissimmee, Florida, United States, 34746
      • Recruiting
      • Clinical Research Site
      • Contact: Clinical Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Clinical Research Site
      • Contact: Clinical Site
  • Oregon
    • Bend, Oregon, United States, 97701
      • Recruiting
      • Clinical Research Site
      • Contact: Clinical Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants willing and able to provide informed consent.

• Participants with diagnosis of pulmonary hypertension (PH) associated with interstitial lung disease (ILD). Diagnosis will be confirmed by a high-resolution computerized tomography (HR-CT) scan showing diffuse parenchymal disease. Eligible diagnosed disease include:

  1. Idiopathic interstitial pneumonia (IIP)
  2. Chronic Hypersensitivity pneumonitis
  3. ILD associated connective tissue disease (CTD)
• Confirmed pulmonary hypertension by right heart catheterization (RHC).
• Ability to perform 6-minute walk distance ≥100 meters.

Exclusion Criteria:

• Diagnosis of PH Group 1 (eg, pulmonary arterial hypertension), Group 2 (related to left heart disease), Group 4 (eg, chronic thromboembolic pulmonary hypertension), or Group 5 (eg, unclassified).
• Exacerbation of underlying lung disease requiring change in therapy or hospitalization within 28 days prior to randomization
• Receiving >10 L/min oxygen supplementation by any mode of delivery at rest
• History of intolerance to mosliciguat, or sGC stimulators or activators.
• Initiation of pulmonary rehabilitation or ongoing acute phase of rehabilitation within 28 days prior to randomization.
• Receipt of investigational or interventional therapy within 42 days OR 5 half-lives (whichever is longer) prior to randomization.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Mosliciguat; Participants will be randomized to receive inhaled mosliciguat or placebo daily for 24 weeks	Drug: Mosliciguat; Dose level 1, 2, or 3 for inhalation; Device: Dry Powder Inhaler; Administration via dry powder inhaler
Placebo Comparator: Matched Placebo; Participants will be randomized to receive inhaled mosliciguat or placebo daily for 24 weeks	Device: Dry Powder Inhaler; Administration via dry powder inhaler; Drug: Placebo; Matching Placebo for inhalation
Experimental: Extension; After Week 24, all participants may receive mosliciguat through an Extension period	Drug: Mosliciguat; Dose level 1, 2, or 3 for inhalation; Device: Dry Powder Inhaler; Administration via dry powder inhaler

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in 6-Minute Walk Distance (6MWD)	The 6MWD measures the distance a participant is able to walk quickly on a flat, hard surface in a period of 6 minutes	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Clinical Worsening (TTCW)	Time from randomization to first occurrence of any of the following events as adjudicated by the independent Event Adjudication Committee (EAC).; Hospitalization >24 hours due to a cardiopulmonary indication; Decrease in 6MWD >15% from baseline directly related to PH-ILD, at two consecutive visits on a different day but no more than 7 days apart; Death (all causes); Lung transplantation for worsening PH (except when pre-planned prior to the trial); Need to initiate additional therapeutic intervention for the treatment of PH	From randomization through Week 24
Percent Change from Baseline in Pulmonary Vascular Resistance (PVR)	PVR evaluated using right heart catheterization (RHC)	Baseline to Week 24
Change from Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)	The NT-ProBNP serum concentrations is a useful biomarker associated with changes in right heart morphology and function. NT-proBNP serum concentration will be assessed to compare the severity of heart failure at Baseline and Week 24.	Baseline to Week 24
Change from Baseline in Living with Pulmonary Fibrosis (L-PF) Total Symptom Score	Change from baseline to Week 24 in L-PF total symptom scores (patient-reported outcome).	Baseline to Week 24

Collaborators and Investigators

• Sponsor: Pulmovant, Inc.
• Investigators: Study Director: Ubaldo Martin, Pulmovant, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2026
• Primary Completion (Estimated): January 28, 2029
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: September 7, 2026
• First Submitted That Met QC Criteria: September 7, 2026
• First Posted (Actual): September 11, 2026

Study Record Updates

• Last Update Posted (Actual): September 11, 2026
• Last Update Submitted That Met QC Criteria: September 7, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: ILD; PH; 6 Minute Walk Distance; mosliciguat
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pathological Conditions, Signs and Symptoms; Cardiovascular Diseases; Fibrosis; Vascular Diseases; Lung Diseases, Interstitial; Hypertension, Pulmonary; Equipment and Supplies; Nebulizers and Vaporizers; Dry Powder Inhalers
• Other Study ID Numbers: RVT-2301-301

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: Yes