An Open Label Extension Study to Evaluate Inhaled Treprostinil in Adult PH With ILD Including CPFE

An Open-Label Extension Study of Inhaled Treprostinil in Subjects With Pulmonary Hypertension Due to Parenchymal Lung Disease

This is a multicenter, open-label trial to evaluate the safety and efficacy of inhaled treprostinil in subjects with pre-capillary pulmonary hypertension (PH) associated with interstitial lung disease (ILD) including combined pulmonary fibrosis and emphysema (CPFE). The study will include about 266 patients who completed all required assessments in the RIN-PH-201 study at approximately 100 clinical trial centers. The study will continue Your participation in this study is voluntary and will last until you discontinue from the study or the study ends. The study will continue until each subject reaches the Week 108 visit or until inhaled treprostinil become commercially available for patients with PH associated with ILD including CPFE (whichever is sooner).

Study Overview

• Status: Terminated
• Conditions: Pulmonary Hypertension; Interstitial Lung Disease; Combined Pulmonary Fibrosis and Emphysema
• Intervention / Treatment: Drug: Inhaled Treprostinil

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Guaynabo, Puerto Rico, 00968
    • Alliance Cardio Pulmonary Research Group, Inc.
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Mobile, Alabama, United States, 36604
      • IMC-Diagnostic & Medical Clinic
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Pulmonary Specialists, Ltd.
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Beverly Hills, California, United States, 90211
      • Cedars-Sinai Medical Center
    • Fresno, California, United States, 93701
      • University of California, San Francisco-Fresno
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90073
      • Department of Veterans Affairs Greater Los Angeles Healthcare System
    • Riverside, California, United States, 92505
      • Pacific Pulmonary Medical Group
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • San Francisco, California, United States, 94115
      • Kaiser Permanente
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Cardiac and Vascular Center
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
    • Washington, District of Columbia, United States, 20010
      • Medstar Heart & Vascular Institute
  • Florida
    • Celebration, Florida, United States, 34747
      • Florida Lung, Asthma & Sleep Specialists, P.A.
    • Clearwater, Florida, United States, 33765
      • St. Francis Sleep, Allergy and Lung Institute
    • Gainesville, Florida, United States, 32610
      • University of Florida Clinical Research Center
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Jacksonville, Florida, United States, 32209
      • University of Florida College of Medicine, Jacksonville
    • Jacksonville, Florida, United States, 33204
      • St. Vincent's Lung, Sleep, and Critical Care Specialists
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32804
      • Florida Hospital
    • Tampa, Florida, United States, 33606
      • University of South Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
    • Austell, Georgia, United States, 30106
      • Piedmont - Georgia Lung Associates
    • Marietta, Georgia, United States, 30060
      • Wellstar Medical Group
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Hospital
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Medical Group, Inc.
    • Indianapolis, Indiana, United States, 46250
      • Community Heart and Vascular Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Physicians Outpatient Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Sciences Center New Orleans
  • Maine
    • South Portland, Maine, United States, 04106
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke'S Hospital of Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Washington University Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • The University of New Mexico
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • New Hyde Park, New York, United States, 11040
      • Northwell Health
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical Center
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina At Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Pinehurst, North Carolina, United States, 28374
      • Pinehurst Medical Clinic, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Health
    • Cincinnati, Ohio, United States, 45219
      • The Carl and Edyth Lindner Research Center at The Christ Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43221
      • The Ohio State University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Pulmonary and Sleep Medicine
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Knoxville, Tennessee, United States, 37919
      • Statcare Pulmonary Consultants
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center at Dallas
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Sciences Center
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist
    • Houston, Texas, United States, 77030
      • The University of Texas health Science Center at Houston
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Science Center at San Antonio
  • Vermont
    • Colchester, Vermont, United States, 05446
      • University of Vermont, Vermont Lung Center
  • Virginia
    • Fairfax, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Norfolk, Virginia, United States, 23507
      • Sentara Cardiovascular Research Institute
    • Richmond, Virginia, United States, 23229
      • Pulmonary Associates of Richmond
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin School of Medicine and Public Health
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin/Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject voluntarily gives informed consent to participate in the study.
2. The subject participated in study RIN-PH-201, remained on study drug, was compliant with RIN-PH-201 study procedures or was enrolled in study RIN-PH-201 at the time that the study was discontinued by the sponsor.

3. Females of reproductive potential must be non-pregnant (as confirmed by a urine pregnancy test at Baseline) and non-lactating, and will:

   • Either abstain from intercourse (when it is in line with their preferred and usual lifestyle), or
   • Use two medically acceptable, highly-effective forms of contraception for the duration of study, and at least 30 days after discontinuing study drug.
4. Males must use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug.

Exclusion Criteria:

1. The subject is pregnant or lactating.
2. The subject was prematurely discontinued from study RIN-PH-201.
3. The subject developed a concurrent illness or condition during the conduct of RIN-PH-201 which, in the opinion of the Investigator, would represent a risk to overall health if they enrolled in this study.

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: Inhaled Treprostinil; Open-label access	Drug: Inhaled Treprostinil; Inhaled treprostinil up to 15 breaths (90 mcg) four times daily; Other Names: Tyvaso

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peak 6-Minute Walk Distance (6MWD) From Baseline	The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out activities of daily living. Change in 6MWD from Baseline correlates with the current clinical standard for assessing patient functional status in the treatment of PH and is considered an objective measure of patient functional status. Subjects will be instructed to walk down a corridor at a comfortable speed as far as they can manage for 6 minutes. Distance <500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance >800 meters (with no rests) suggests mild or no limitation. Peak exposure 6MWD will occur by conducting 6MWT within 10 to 60 minutes after the most recent dose of study drug dose.	Baseline through Week 124 in RIN-PH-202 (Combined data from parent study RIN-PH-201 [NCT02630316] and this open-label extension study RIN-PH-202)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Plasma Concentration of N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) From Baseline	The N-terminal pro-BNP (NT-proBNP) serum concentration 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 each visit through Week 124. Blood for NT-proBNP assessment must be drawn prior to conducting the 6-minute walk test (6MWT).	Baseline through Week 124 in RIN-PH-202 (Combined data from parent study RIN-PH-201 [NCT02630316] and this open-label extension study RIN-PH-202)
Change in Percent Predicted Forced Vital Capacity (FVC) From Baseline	Change in pulmonary function following inhaled treprostinil therapy will be measured by Forced Vital Capacity (FVC), calculated from a Pulmonary Function Test (PFT) performed at Baseline and Weeks 12, 48, and 108.	Baseline and Weeks 12, 48, and 108

Collaborators and Investigators

• Sponsor: United Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2016
• Primary Completion (Actual): August 1, 2021
• Study Completion (Actual): August 1, 2021

Study Registration Dates

• First Submitted: December 11, 2015
• First Submitted That Met QC Criteria: December 14, 2015
• First Posted (Estimate): December 17, 2015

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: November 8, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: ILD; PH; Treprostinil; 6 Minute Walk Test; CPFE
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Hypertension; Lung Diseases; Emphysema; Pulmonary Fibrosis; Hypertension, Pulmonary; Lung Diseases, Interstitial; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: RIN-PH-202