Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis (TETON-1)

A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis (TETON-1)

Study RIN-PF-301 is designed to evaluate the superiority of inhaled treprostinil against placebo for the change in absolute forced vital capacity (FVC) from baseline to Week 52.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis; Interstitial Lung Disease
• Intervention / Treatment: Drug: Placebo; Device: Treprostinil Ultrasonic Nebulizer; Drug: Inhaled Treprostinil

Detailed Description

Study RIN-PF-301 is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the superiority of inhaled treprostinil against placebo for the change in absolute FVC in subjects with IPF over a 52-week period. Subjects will be randomly allocated 1:1 to receive inhaled treprostinil or placebo. All subjects will initiate inhaled treprostinil or placebo at a dose of 3 breaths administered 4 times daily (QID) and will titrate to a target dosing regimen of 12 breaths QID. Study drug doses may be titrated up as tolerated, until the target dose or maximum clinically tolerated dose is achieved. Once eligible, 6 Treatment Period visits to the clinic will be required at Weeks 4, 8, 16, 28, 40, and 52.

Efficacy assessments include spirometry (FVC), time to clinical worsening, time to first acute exacerbation of IPF, overall survival, King's Brief Interstitial Lung Disease (K-BILD) questionnaire, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, supplemental oxygen use, and lung diffusion capacity (DLCO). Safety assessments include the development of adverse events (AEs)/serious adverse events (SAEs), vital signs, clinical laboratory parameters, and electrocardiogram (ECG) parameters.

Subjects who complete the Week 52 Visit may be offered the opportunity to enter an open-label extension (OLE) study after completing the final study visit.

• Study Type: Interventional
• Enrollment (Actual): 598
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4G5
    • Institut Universitaire de Cardiologie et de Pneumologie de Quebec-Universite
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • St.Paul's Hospital
  • Ontario
    • Ajax, Ontario, Canada, L1S 2J5
      • Dynamic Drug Advancement Limited
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
  • Quebec
    • Trois-Rivières, Quebec, Canada, G8T 7A1
      • Centre d'investigation Clinique Mauricie
• Chile
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 7630226
      • Fundacion Medica San Cristobal
  • Valparaiso
    • Quillota, Valparaiso, Chile, 2260000
      • Centro Respiratorio Integral LTDA. (CENRESIN)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Pulmonary Specialists, Ltd.
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center-Phoenix
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center - Norton Thoracic Institute
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • La Jolla, California, United States, 92037
      • UC San Diego Health
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
    • Newport Beach, California, United States, 92663
      • NewportNativeMD, Inc
    • Orange, California, United States, 92868
      • University of California, Irvine
    • Palm Springs, California, United States, 92262
      • Palmtree Clinical Research, Inc.
    • Sacramento, California, United States, 95817
      • UC Davis Health Medical Center
    • San Francisco, California, United States, 94143
      • University of California - San Francisco
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Clearwater, Florida, United States, 33765
      • St. Francis Sleep Allergy & Lung Institute
    • Gainesville, Florida, United States, 32610
      • University of Florida Health at Shands
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Jacksonville, Florida, United States, 32204
      • Ascension St. Vincent's
    • Jacksonville, Florida, United States, 32209
      • University of Florida
    • Kissimmee, Florida, United States, 34741
      • Pulmonary Disease Specialists, PA d/b/a PDS Research
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group, PA
    • St. Petersburg, Florida, United States, 33704
      • Coastal Pulmonary & Critical Care PLC
    • Tampa, Florida, United States, 33606
      • University of South Florida Health
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30309
      • Piedmont Healthcare Atlanta
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • The Queen's Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center Outpatient Pulmonary Clinic
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Community Health Network
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
    • Louisville, Kentucky, United States, 40202
      • Norton Pulmonary Specialists
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Medical Center
    • New Orleans, Louisiana, United States, 70112
      • LSU Health Sciences Center New Orleans
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Science Center Shreveport
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Asthma & Allergy Center
    • Silver Spring, Maryland, United States, 20904
      • Adventist Healthcare White Oak 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
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Int Med Pulmonary and Critical Care
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Royal Oak, Michigan, United States, 48073
      • Corewell Health William Beaumont Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • The Lung Research Center
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • Creighton University Clinical Research Office
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Health Sciences Center
  • New York
    • Liverpool, New York, United States, 13088
      • St Joseph's Physician's Pulmonary Health
    • New Hyde Park, New York, United States, 11040
      • Northwell Health
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Stony Brook, New York, United States, 11725
      • Stony Brook Advanced Specialty Care
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • Pulmonix, LLC
    • Greenville, North Carolina, United States, 27834
      • East Carolina University and Leo Jenkins Cancer Center
    • Winston-Salem, North Carolina, United States, 27103
      • Southeastern Research Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43221
      • The Ohio State University Wexner Medical Center - Martha Morehouse Medical Pavilion
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97220
      • The Oregon Clinic, PC
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center/Penn State College of Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple Lung Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thoams Jefferson,Hospital University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Columbia, South Carolina, United States, 29203
      • Prisma Health Midlands
    • Rock Hill, South Carolina, United States, 29732
      • Clinical Research of Rock Hill
  • Tennessee
    • Knoxville, Tennessee, United States, 37919
      • Statecare Pulmonary Consultants
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Dallas, Texas, United States, 75390-8550
      • Univrsity of Texas Southwestern Medical Center
    • Denison, Texas, United States, 75020
      • Premier Pulmonary Critical Care and Sleep Medicine
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
    • Houston, Texas, United States, 77030
      • Baylor Clinic-Baylor College of Medicine
    • McAllen, Texas, United States, 78503
      • A & A Research Consultants, LLC
    • McKinney, Texas, United States, 75069
      • Metroplex Pulmonary and Sleep Center PA
    • The Woodlands, Texas, United States, 77380
      • Renovatio Clinical Consultants, LLC
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Richmond, Virginia, United States, 23230
      • Pulmonary Associates of Richmond, Inc.
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin School of Medicine and Public Health
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject gives voluntary informed consent to participate in the study.
2. Subject is ≥40 years of age, inclusive, at the time of signing informed consent.
3. The subject has a diagnosis of IPF based on the 2018 ATS/ERS/JRS/ALAT Clinical Practice Guideline (Raghu 2018) and confirmed by central review of high-resolution computed tomography (HRCT) (performed within the previous 12 months), and if available, surgical lung biopsy.
4. FVC ≥45% predicted at Screening.
5. Subjects on pirfenidone or nintedanib must be on a stable and optimized dose for ≥30 days prior to Baseline. Concomitant use of both pirfenidone and nintedanib is not permitted.
6. Women of childbearing potential must be non-pregnant (as confirmed by a urine pregnancy test at Screening and Baseline) and non-lactating, and will abstain from intercourse (when it is in line with their preferred and usual lifestyle) or use 2 medically acceptable, highly effective forms of contraception for the duration of the study, and at least 30 days after discontinuing study drug.
7. Males with a partner of childbearing potential must use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug.
8. In the opinion of the Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.

Exclusion Criteria:

1. Subject is pregnant or lactating.
2. Subject has primary obstructive airway physiology: FEV1/FVC <0.70 at Screening.
3. The subject has shown intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to effectively titrate that therapy.
4. The subject has received any PAH-approved therapy, including prostacyclin therapy (epoprostenol, treprostinil, iloprost, or beraprost; except for acute vasoreactivity testing), IP receptor agonists (selexipag), endothelin receptor antagonists, phosphodiesterase type 5 inhibitors (PDE5-Is), or soluble guanylate cyclase stimulators within 60 days prior to Baseline. As needed use of a PDE5-I for erectile dysfunction is permitted, provided no doses are taken within 48 hours of any study-related efficacy assessments.
5. Use of any of the following medications: azathioprine (AZA), cyclosporine, mycophenolate mofetil, tacrolimus, oral corticosteroids (OCS) >20 mg/day or the combination of OCS+AZA+N-acetylcysteine within 30 days prior to Baseline; cyclophosphamide within 60 days prior to Baseline; or rituximab within 6 months prior to Baseline.
6. The subject is receiving >10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
7. Exacerbation of IPF or active pulmonary or upper respiratory infection within 30 days prior to Baseline. Subjects must have completed any antibiotic or steroid regimens for treatment of the infection or acute exacerbation more than 30 days prior to Baseline to be eligible. If hospitalized for an acute exacerbation of IPF or a pulmonary or upper respiratory infection, subjects must have been discharged more than 90 days prior to Baseline to be eligible.
8. Uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline.
9. In the opinion of the Investigator, the subject has any condition that would interfere with the interpretation of study assessments or would impair study participation or cooperation.
10. Use of any other investigational drug/device or participation in any investigational study in which the subject received a medical intervention (ie, procedure, device, medication/supplement) within 30 days prior to Screening. Subjects participating in non-interventional, observational, or registry studies are eligible.
11. Life expectancy <6 months due to IPF or a concomitant illness.
12. Acute pulmonary embolism within 90 days prior to Baseline.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo inhaled using an ultrasonic nebulizer QID	Drug: Placebo; Placebo administered QID; Device: Treprostinil Ultrasonic Nebulizer; Treprostinil ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.
Experimental: Inhaled Treprostinil; Treprostinil for inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath. Inhaled QID and titrated up to a target of 12 breaths QID or until the subject reaches their maximum clinically tolerated dose.	Device: Treprostinil Ultrasonic Nebulizer; Treprostinil ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.; Drug: Inhaled Treprostinil; Inhaled treprostinil (6 mcg/breath) administered QID; Other Names: Tyvaso

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Absolute FVC from Baseline to Week 52	The FVC measurement indicates the amount of air a person can forcefully and quickly exhale after taking a deep breath.	Baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Clinical Worsening	Clinical worsening was monitored from randomization until 1 of the following criteria were met: death (all causes), hospitalization due to a respiratory indication, or 10% relative decline in % predicted FVC.	Baseline to Week 52
Time to First Acute Exacerbation of IPF	An exacerbation of IPF is defined as an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality.	Baseline to Week 52
Change in % Predicted FVC from Baseline to Week 52	The FVC measurement indicates the amount of air a person can forcefully and quickly exhale after taking a deep breath. Percent predicted FVC is calculated based on factors such as ethnicity, sex, age, height, and weight.	Baseline to Week 52
Change in K-BILD Questionnaire Score from Baseline to Week 52	The K-BILD is a self-administered, 15-item questionnaire validated for patients with interstitial lung disease (ILD) consisting of 3 domains (breathlessness and activities, psychological, and chest symptoms).	Baseline to Week 52
Overall Survival at Week 52	Vital status will be assessed for all subjects at Week 52, including those who discontinue the study prematurely or who withdraw consent.	Week 52
Change in DLCO from Baseline to Week 52	The DLCO measurement measures how well oxygen moves from the lungs to the blood.	Baseline to Week 52

Collaborators and Investigators

• Sponsor: United Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): February 2, 2026
• Study Completion (Actual): February 2, 2026

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ILD; Treprostinil; IPF
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Substandard Drugs; Pharmaceutical Preparations; treprostinil
• Other Study ID Numbers: RIN-PF-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No