A Phase 3 Study to Evaluate the Safety and Tolerability of L606 in Subjects With PAH or PH-ILD

A Phase 3, 2-Part, Open-Label Study to Evaluate the Safety and Tolerability of Liposomal Treprostinil Inhalation Suspension (L606) in Subjects With Pulmonary Arterial Hypertension or Pulmonary Hypertension Associated With Interstitial Lung Disease

This Phase 3, 2-part, open-label, multicenter study aims to demonstrate the safety and tolerability of L606 in patients with PAH or PH-ILD. The study will determine the short-term and long-term safety and tolerability of L606 in this patient population.

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Arterial Hypertension; Pulmonary Hypertension Due to Lung Diseases
• Intervention / Treatment: Combination product: L606 inhalation suspension

Detailed Description

This Phase 3, 2-part, open-label, multicenter study aims to demonstrate the safety and tolerability of repeated doses of L606 in patients with PAH or PH-ILD.

Cohort A: Subjects with PAH or PH-ILD receiving prior stable doses of Tyvaso and willing to switch to L606.

Cohort B: Subjects with PAH (not initially on prostacyclin therapy) who are likely to receive clinical benefit from inhaled treprostinil based on the opinion of the investigator.

Cohort A subjects will sequentially participate in the Main Study Period (MSP) for 2 weeks and the Open Extension Period (OEP) for 46 weeks. Cohort B subjects will sequentially participate in the MSP for 12 weeks and the OEP for 36 weeks.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Arizona Pulmonary Specialists
  • California
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Tampa, Florida, United States, 33606
      • University Of South Florida
  • New York
    • New York, New York, United States, 10029-6504
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Medical Center
  • Oregon
    • Bend, Oregon, United States, 97701
      • Summit Health Eastside Clinic
  • Texas
    • Temple, Texas, United States, 76508
      • Baylor Scott and White Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Males and females ≥18 and ≤80 years of age.

2. Diagnosed with

   1. PAH belonging to at least 1 of the following subgroups of Group 1 pulmonary hypertension (PH) per European Society of Cardiology/European Respiratory Society Guidelines for the diagnosis and treatment of PH at least 1 year prior to screening. or
   2. PH-ILD Group 3 European Society of Cardiology/European Respiratory Society Guidelines for the diagnosis and treatment of PH. Subjects with Group 3 PH that is not related to underlying ILD are not eligible.

3. Subjects with PAH: Documentation of having PAH as confirmed by RHC meeting the following criteria:

   i. Mean PAP >20 mmHg. ii. Pulmonary arterial wedge pressure ≤15 mmHg. iii. Pulmonary vascular resistance >3 Wood units. Subjects with PH-ILD: Confirmation of the underlying ILD must be based on HRCT imaging with demonstration of diffuse parenchymal lung disease and documented by the Investigator or radiology report. Subjects may have any form of ILD or CPFE.

4. NYHA functional class II, III, or IV at the screening visit.
5. Can complete a screening 6MWD of ≥150 meters
6. For subjects with PAH: >65% of predicted and FEV1/FVC ratio >65% at screening. For subjects with PH-ILD: >40% of predicted and FEV1/FVC ratio >70% at screening.

Key Exclusion Criteria:

1. LVEF of ≤45% on a historical echocardiogram.
2. History of sleep apnea, or left-sided heart disease (including but not limited to aortic or mitral valve disease, pericardial constriction, restrictive or congestive cardiomyopathy, or coronary artery disease) per investigator's discretion.
3. Experienced an acute exacerbation of disease or hospitalization for any reason within 30 days of signing the ICF or prior to baseline.
4. Musculoskeletal disorder (eg, arthritis affecting the lower limbs, recent hip or knee joint replacement) or any disease that would likely be the primary limit to ambulation or subject is connected to a machine that is not portable enough to allow for a 6MWT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L606	Combination product: L606 inhalation suspension; L606 inhalation suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety/Tolerability assessed by incidence of treatment-emergent AEs/SAEs	(MSP for Cohort A): Proportion of patients with PAH or PH-ILD on a stable Tyvaso dose who would develop treatment-emergent AEs/SAEs after switching to L606 dosing for up to 2 weeks during MSP.	2 weeks
Safety/Tolerability assessed by incidence of treatment-emergent AEs/SAEs	(MSP for Cohort B): Proportion of patients with PAH (not initially on prostacyclin therapy) who would develop treatment-emergent AEs/SAEs during 12 weeks of the MSP with titration on twice daily L606.	12 weeks
Safety/Tolerability assessed by incidence of treatment-emergent AEs/SAEs (long-term)	(OEP for Cohorts A and B): Proportion of subjects with PAH or PH-ILD, choosing to continue twice daily L606 dosing for up to 48 weeks, who would develop treatment emergent AEs/SAEs up to 48 hours after the last dose.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety/Tolerability assessed by incidence of treatment-emergent AEs/SAEs	Proportion of patients with PAH on a stable Tyvaso dose (4 times/day) who continue twice daily L606 dosing beyond 2 weeks, who would develop treatment-emergent AEs/SAEs for up to 12 months.	12 months
Pharmacokinetics assessed by steady-state PK parameters of treprostinil from Tyvaso and L606	Ratio (L606 at Week 2/Tyvaso at Day 1) of geometric means of average steady-state plasma concentrations of treprostinil (calculated over the dosing interval as Cavg) in patients with PAH or PH-ILD, assuming compliance with dosing requirements up to steady state.	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of L606 assessed by 6MWD at steady-state morning trough and peak concentrations of treprostinil	Cohort A: In patients with PAH or PH-ILD transitioning from Tyvaso, the mean difference in 6MWD at steadystate: morning trough, peak, and peak minus trough after twice daily L606 for 2 weeks compared to baseline (Tyvaso at Day 1) Cohort B: In patients with PAH (not initially on prostacyclin therapy) after 12 weeks of twice daily L606 dosing, the mean difference in 6MWD at 60-90 minutes after morning dose compared to pre-dose baseline	2 weeks and 12 weeks
Efficacy of L606 assessed by 6MWD at steady-state morning trough and peak concentrations of treprostinil (long-term)	Cohort A and Cohort B: In patients with PAH or PH-ILD choosing to continue twice daily L606 dosing for up to 48 weeks, the mean difference in 6MWD at steady-state trough after 48 weeks and at peaks at 60-90 minutes after morning dose at 12, 24, 36 and 48 weeks compared to baseline measurements.	48 weeks
Cohort A and Cohort B: Quality of Life assessed by PAH-specific Quality of Life questionnaire Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR).	Cohort A: In patients with PAH or PH-ILD transitioning from Tyvaso, the difference in mean CAMPHOR (for total score, symptom, activity, and QoL components), after receiving a twice daily dose of L606 for 2 weeks compared to Tyvaso at Day 1. Cohort B: In patients with PAH (not initially on prostacyclin therapy) after 12 weeks with titration on twice daily dose of L606 compared to pre-dose. For Cohort A and Cohort B (long-term): In patients who choose to continue twice daily L606 dosing (for up to 48 weeks) compared to pre-transition/pre-dose.	2 weeks, 12 weeks, 48 weeks
Treatment satisfaction of L606 assessed by Treatment Satisfaction Questionnaire (TSQM)	Cohort A: In patients with PAH or PH-ILD transitioning from Tyvaso, the difference in mean TSQM score (effectiveness, side effects, convenience, and global satisfaction components) after receiving twice daily doses of L606 for 2 weeks or at treatment discontinuation. Cohort B: In patients with PAH after receiving a twice daily dose of L606 for 12 weeks or at treatment discontinuation, the mean TSQM score irrespective of compliance with the dosing regimen or taking of prohibited medication. For Cohort A and Cohort B: In patients with PAH or PH-ILD who choose to continue twice daily L606 dosing beyond 2 weeks of the MSP for Cohort A or patients with PAH who choose to continue twice daily L606 dosing beyond 12 weeks of the MSP for Cohort B, the mean TSQM score at 12 weeks or at treatment discontinuation, irrespective of compliance with the dosing regimen or taking of prohibited medication.	2 weeks, 12 weeks and 48 weeks
Efficacy of L606 assessed by Borg Dyspnea Score	Mean and mean difference in Borg Dyspnea Score from baseline at steady-state; morning trough, peak, and peak minus trough after the 6MWT and twice daily L606 dosing during (A) 2 weeks for Cohort A or (B) peak only at 12 weeks for Cohort B; troughs and peaks after the 6MWT, for up to 48 weeks in patients who choose to continue L606 dosing beyond (A) 2 weeks for Cohort A or (B) 12 weeks for Cohort B Mean and mean difference from Day 1 in Borg Dyspnea Score at each time point before the 6MWT and the mean changes in Borg Dyspnea Score from before to immediately after 6MWT.	2 weeks, 12 weeks and 48 weeks
Efficacy of L606 assessed by New York Heart Association (NYHA) functional class	Proportion of patients with each grade of NYHA functional class on Day 1 (baseline), end of MSP (Cohorts A and B), and across the OEP (ie, start of the OEP to 48 weeks).	2 weeks, 12 weeks and 48 weeks
Efficacy of L606 assessed by N-terminal prohormone B-type natriuretic peptide (NT-proBNP)	Mean and mean difference in NT-proBNP levels from Day 1 (baseline) to the end of MSP (Cohorts A and B), and across the OEP (ie, start of the OEP to 48 weeks).	2 weeks, 12 weeks and 48 weeks
PAH and PH-ILD symptoms	Mean and mean difference in PAH or PH-ILD symptoms score from Day 1 (baseline) to the end of MSP (Cohorts A and B), and across the OEP (ie, start of the OEP to 48 weeks).	2 weeks, 12 weeks and 48 weeks
L606 treatment failure due to worsening of PAH or PH-ILD	Incidence rate of L606 treatment failure due to worsening of PAH or PH-ILD, where worsening is defined as discontinuation of L606 due to disease progression, death, transplantation, hospital stay due to worsening PAH or PH-ILD, or initiation of additional approved or new PAH or PH-ILD therapy.	2 weeks, 12 weeks and 48 weeks

Collaborators and Investigators

• Sponsor: Liquidia Technologies, Inc.
• Collaborators: PPD Development, LP
• Investigators: Principal Investigator: Jeremy P Feldman, MD, Arizona Pulmonary Specialists; Principal Investigator: Elizabeth Gay, MD, Brigham and Women's Hospital; Principal Investigator: Michael G Risbano, MD, UPMC Montefiore

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Actual): March 20, 2025
• Study Completion (Estimated): March 31, 2031

Study Registration Dates

• First Submitted: December 21, 2020
• First Submitted That Met QC Criteria: December 27, 2020
• First Posted (Actual): December 31, 2020

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: inhalation; Pulmonary Arterial Hypertension; treprostinil; Pulmonary Hypertension Due to Lung Diseases
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Hypertension, Pulmonary; Pathological Conditions, Signs and Symptoms; Pulmonary Arterial Hypertension; Respiratory Aspiration
• Other Study ID Numbers: PBI L606p3

Drug and device information, study documents

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