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Idiopathic Pulmonary FibrosisPhase 3TETON-1NCT04708782

Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis

A Phase 3 study testing Inhaled Treprostinil and Treprostinil Ultrasonic Nebulizer in people with Idiopathic Pulmonary Fibrosis and Interstitial Lung Disease, run by United Therapeutics at 98 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 40 years and older
What is being tested?
Inhaled Treprostinil and Treprostinil Ultrasonic Nebulizer
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
598 participants
Where
98 sitesin 3 countries
Study dates
1 Jun 2021to 2 Feb 2026
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject gives voluntary informed consent to participate in the study.
  • Subject is ≥40 years of age, inclusive, at the time of signing informed consent.
  • 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.
  • FVC ≥45% predicted at Screening.
  • 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.
  • 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.
  • 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.
  • 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.

Who cannot join

  • Subject is pregnant or lactating.
  • Subject has primary obstructive airway physiology: FEV1/FVC <0.70 at Screening.
  • 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.
  • 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.
  • 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.
  • The subject is receiving >10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
Show all 12Show fewer
  • 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.
  • Uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline.
  • 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.
  • 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.
  • Life expectancy <6 months due to IPF or a concomitant illness.
  • Acute pulmonary embolism within 90 days prior to Baseline.

Trial locations and contacts

98 sites in 3 countries.

98 sites in 3 countries

United States90 sites

  • University of New Mexico Health Sciences Center

    Albuquerque, New Mexico, 87106

  • University of Michigan Int Med Pulmonary and critical care

    Ann Arbor, Michigan, 48109

  • Piedmont Healthcare Atlanta

    Atlanta, Georgia, 30309

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • Johns Hopkins Asthma & Allergy Center

    Baltimore, Maryland, 21224

  • The University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Health System

    Charlottesville, Virginia, 22903

  • The Lung Research Center

    Chesterfield, Missouri, 63017

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • Rush University Medical Center Outpatient Pulmonary Clinic

    Chicago, Illinois, 60612

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • St. Francis Sleep Allergy & Lung Institute

    Clearwater, Florida, 33765

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Prisma Health Midlands

    Columbia, South Carolina, 29203

  • The Ohio State University Wexner Medical Center - Martha Morehouse Medical Pavilion

    Columbus, Ohio, 43221

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • Univrsity of Texas Southwestern Medical Center

    Dallas, Texas, 75390-8550

  • Premier Pulmonary Critical Care and Sleep Medicine

    Denison, Texas, 75020

  • National Jewish Health

    Denver, Colorado, 80206

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • University of Florida Health at Shands

    Gainesville, Florida, 32610

  • PulmonIx, LLC

    Greensboro, North Carolina, 27403

  • East Carolina University and Leo Jenkins Cancer Center

    Greenville, North Carolina, 27834

  • Penn State Milton S. Hershey Medical Center/Penn State College of Medicine

    Hershey, Pennsylvania, 17033

  • The Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Baylor Clinic-Baylor College of Medicine

    Houston, Texas, 77030

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77030

  • Community Health Network

    Indianapolis, Indiana, 46250

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Ascension St. Vincent's

    Jacksonville, Florida, 32204

  • University of Florida

    Jacksonville, Florida, 32209

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • The University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • Pulmonary Disease Specialists, PA d/b/a PDS Research

    Kissimmee, Florida, 34741

  • Statecare Pulmonary Consultants

    Knoxville, Tennessee, 37919

  • UC San Diego Health

    La Jolla, California, 92037

  • St Joseph's Physician's Pulmonary Health

    Liverpool, New York, 13088

  • David Geffen School of Medicine at UCLA

    Los Angeles, California, 90095

  • Norton Pulmonary Specialists

    Louisville, Kentucky, 40202

  • University of Louisville

    Louisville, Kentucky, 40202

  • University of Wisconsin School of Medicine and Public health

    Madison, Wisconsin, 53792

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • A & A Research Consultants, LLC

    McAllen, Texas, 78503

  • Metroplex Pulmonary and Sleep Center PA

    McKinney, Texas, 75069

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Intermountain Medical Center

    Murray, Utah, 84107

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37204

  • Northwell Health

    New Hyde Park, New York, 11040

  • LSU Health Sciences Center New Orleans

    New Orleans, Louisiana, 70112

  • Tulane University Medical Center

    New Orleans, Louisiana, 70112

  • NewportNativeMD, Inc

    Newport Beach, California, 92663

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Creighton University Clinical Research Office

    Omaha, Nebraska, 68124

  • University of California, Irvine

    Orange, California, 92868

  • Central Florida Pulmonary Group, PA

    Orlando, Florida, 32803

  • Palmtree Clinical Research, Inc.

    Palm Springs, California, 92262

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Thoams Jefferson,Hospital University

    Philadelphia, Pennsylvania, 19107

  • Temple Lung Center

    Philadelphia, Pennsylvania, 19140

  • Banner University Medical Center-Phoenix

    Phoenix, Arizona, 85006

  • Arizona Pulmonary Specialists, Ltd.

    Phoenix, Arizona, 85012

  • St. Joseph's Hospital and Medical Center - Norton Thoracic Institute

    Phoenix, Arizona, 85013

  • The Oregon Clinic, PC

    Portland, Oregon, 97220

  • Pulmonary Associates of Richmond, Inc.

    Richmond, Virginia, 23230

  • Mayo Clinic

    Rochester, Minnesota, 55902

  • University of Rochester Medical center

    Rochester, New York, 14642

  • Clinical Research of Rock Hill

    Rock Hill, South Carolina, 29732

  • Corewell Health William Beaumont Hospital

    Royal Oak, Michigan, 48073

  • UC Davis Health Medical Center

    Sacramento, California, 95817

  • University of Utah Health

    Salt Lake City, Utah, 84108

  • University of California - San Francisco

    San Francisco, California, 94143

  • LSU Health Science Center Shreveport

    Shreveport, Louisiana, 71103

  • Adventist Healthcare White Oak Medical CEnter

    Silver Spring, Maryland, 20904

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Coastal Pulmonary & Critical Care PLC

    St. Petersburg, Florida, 33704

  • Stanford University Medical Center

    Stanford, California, 94305

  • Stony Brook Advanced Specialty Care

    Stony Brook, New York, 11725

  • University of South Florida Health

    Tampa, Florida, 33606

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Renovatio Clinical Consultants, LLC

    The Woodlands, Texas, 77380

  • University of Arizona

    Tucson, Arizona, 85724

  • Cleveland Clinic Florida

    Weston, Florida, 33331

  • Southeastern Research Center

    Winston-Salem, North Carolina, 27103

Other trials in United States

Canada6 sites

  • Dynamic Drug Advancement Limited

    Ajax, Ontario, L1S 2J5

  • St. Joseph's Healthcare Hamilton

    Hamilton, Ontario, L8N 4A6

  • Institut Universitaire de Cardiologie et de Pneumologie de Quebec-Universite

    Québec, G1V 4G5

  • Toronto General Hospital

    Toronto, Ontario, M5G 2C4

  • Centre d'investigation Clinique Mauricie

    Trois-Rivières, Quebec, G8T 7A1

  • St.Paul's Hospital

    Vancouver, British Columbia, V6Z1Y6

Other trials in Canada

Chile2 sites

  • Centro Respiratorio Integral LTDA. (CENRESIN)

    Quillota, Valparaiso, 2260000

  • Fundacion Medica San Cristobal

    Santiago, Santiago Metropolitan, 7630226

Other trials in Chile

About this study

Official title: 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.

Read the 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.

Being tested
Placebo, Inhaled Treprostinil, Treprostinil Ultrasonic Nebulizer
Keywords
Treprostinil, IPF, ILD
Medical subject headings
Idiopathic Pulmonary Fibrosis, Lung Diseases, Interstitial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Placebo administered QID

  • Inhaled TreprostinilDrug

    Also called Tyvaso

    Inhaled treprostinil (6 mcg/breath) administered QID

  • Treprostinil Ultrasonic NebulizerDevice

    Treprostinil ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.

Study groups in NCT04708782
Study groupRoleWhat they receive
PlaceboPlacebo comparatorMatching placebo inhaled using an ultrasonic nebulizer QID
Receives: Drug: Placebo; Device: Treprostinil Ultrasonic Nebulizer
Inhaled TreprostinilExperimentalTreprostinil 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.
Receives: Drug: Inhaled Treprostinil; Device: Treprostinil Ultrasonic Nebulizer

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to Week 52

Secondary outcomes (6)

  1. 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.

    Measured: Baseline to Week 52

  2. 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.

    Measured: Baseline to Week 52

  3. 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.

    Measured: Week 52

  4. 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.

    Measured: Baseline to Week 52

  5. 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).

    Measured: Baseline to Week 52

  6. Change in DLCO from Baseline to Week 52

    The DLCO measurement measures how well oxygen moves from the lungs to the blood.

    Measured: Baseline to Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jan 2021
  2. Study start1 Jun 2021
  3. Primary completion2 Feb 2026
  4. Study completion2 Feb 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
598 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04708782
Sponsor's protocol ID
RIN-PF-301
Acronym
TETON-1
Status last verified
May 2026
First submitted
12 Jan 2021
Last updated
5 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes

Publications

  • Hwang S, Fuentes M, Lederer J, Mitkus S, Rivas-Fuentes S, Nathan SD. A plain language review of the TETON-1 and TETON-2 studies: inhaled treprostinil (Tyvaso) in idiopathic pulmonary fibrosis. Expert Rev Respir Med. 2026 Nov 2:1-10. doi: 10.1080/17476348.2026.2743298. Online ahead of print.

    PubMed 42972641

  • Nathan SD, Smith P, Deng C, Golden J, Reynaud-Gaubert M, Farr G, Bregman B, Crossno PF, Harari S, Gupta N, Jouneau S, Adir Y, Molina-Molina M, Breytenbach N, Peterson L, Bell H, Zywot E, Rao Y, Flaherty KR, Cottin V, Behr J; TETON-1 and TETON-2 Trial Investigators. Combined results of the TETON-1 and TETON-2 Trials of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2026 Sep 23:aamag507. doi: 10.1093/ajrccm/aamag507. Online ahead of print.

    PubMed 42776606

  • Nathan SD, Smith P, Deng C, King CS, De Salvo M, Weigt SS, Pandya S, Bandyopadhyay D, Lasky JA, Krishna R, Hambly N, Ramaswamy M, Kebbe J, Ettinger N, Gao J, Rao Y, Breytenbach N, Peterson L, Bell H, Behr J, Cottin V, Flaherty KR; TETON-1 Trial Investigators. Phase 3 Trials of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. N Engl J Med. 2026 Jul 9;395(2):115-126. doi: 10.1056/NEJMoa2501488. Epub 2026 May 18.

    PubMed 42149993

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Inhaled Treprostinil and Treprostinil Ultrasonic Nebulizer in people with Idiopathic Pulmonary Fibrosis and Interstitial Lung Disease, run by United Therapeutics at 98 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 98 sites in United States, Canada, Chile. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Absolute FVC from Baseline to Week 52 (time frame: Baseline to Week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04708782, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.

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