Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified April 2026 by United Therapeutics
Sponsor
United Therapeutics
Information Provided by (Responsible Party)
United Therapeutics
Clinicaltrials.gov Identifier
NCT05943535
Other Study ID Numbers:
RIN-PF-305
First Submitted
July 4, 2023
First Posted
July 12, 2023
Last Update Posted
May 6, 2026
Last Verified
April 2026

ClinicalTrials.gov processed this data on May 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Study RIN-PF-305 is a Phase 3, multinational, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of inhaled treprostinil in subjects with PPF 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 (forced vital capacity \[FVC\]), time to clinical worsening, time to first acute exacerbation of interstitial lung disease (ILD), 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.

Condition or DiseaseIntervention/Treatment
Progressive Pulmonary FibrosisInterstitial Lung Disease
Drug: PlaceboDrug: Inhaled Treprostinil

Study Design

Study TypeInterventional
Actual Enrollment698 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Randomized, Double-blind, Placebo-controlled, Multinational, Phase 3 Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
Study Start DateOctober 29, 2023
Actual Primary Completion Date1yr 5mos from now
Actual Study Completion Date1yr 5mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Placebo
Matching placebo inhaled using an ultrasonic nebulizer QID
Drug: Placebo
Placebo administered QID
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.
Drug: Inhaled Treprostinil
Inhaled treprostinil (6 mcg/breath) administered QID

Outcome Measures

Primary Outcome Measures
  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.
Secondary Outcome Measures
  1. Time to First Clinical Worsening
    Clinical worsening is monitored from randomization until 1 of the following criteria are met: death (all causes), hospitalization due to a respiratory indication, or ≥10% relative decline in % predicted FVC.
  2. Time to First Acute Exacerbation of ILD
    An exacerbation of ILD is defined as an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality.
  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.
  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 race, sex, age, height, and weight.
  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 ILD consisting of 3 domains (breathlessness and activities, psychological, and chest symptoms).
  6. Change in DLCO from Baseline to Week 52
    The DLCO measurement measures how well oxygen moves from the lungs to the blood.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. Subject gives voluntary informed consent to participate in the study. 2. Subject is ≥18 years of age, inclusive, at the time of signing informed consent. 3. Subject has radiological evidence of pulmonary fibrosis of \>10% extent on an HRCT scan in the previous 12 months (confirmed by central review). 4. Subject has a diagnosis of PPF (other than IPF) that fulfills at least 1 of the following criteria for progression within 24 months of screening despite standard treatment of ILD, as assessed by the Investigator: 1. Clinically significant decline in % predicted FVC based on ≥10% relative decline 2. Marginal decline in % predicted FVC based on ≥5% to \<10% relative decline combined with worsening of respiratory symptoms 3. Marginal decline in % predicted FVC based on ≥5% to \<10% relative decline combined with increasing extent of fibrotic changes on chest imaging 4. Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging 5. FVC ≥45% predicted at Screening (confirmed by central review). 6. Subjects must be on 1 of the following: 1. On nintedanib or pirfenidone for ≥90 days prior to Baseline and in the Investigator's opinion, are planning to continue treatment through the study 2. Not on treatment with nintedanib or pirfenidone for ≥90 days prior to Baseline and in the Investigator's opinion, not planning to initiate either treatment during the study. Concomitant use of both nintedanib and pirfenidone is not permitted. 7. Subjects treated with immunosuppressive agents (eg, mycophenolate, methotrexate, azathioprine, oral corticosteroids, rituximab) need to be on treatment for at least 120 days prior to Baseline and, in the Investigator's clinical opinion, must be refractory to treatment. 8. Women of childbearing potential must be non-pregnant (as confirmed by a urine pregnancy test at Screening and Baseline) and non-lactating, and will agree to do 1 of the following: 1. Abstain from intercourse (when it is in line with their preferred and usual lifestyle) 2. Use 2 medically acceptable, highly effective forms of contraception for the duration of the study, and at least 30 days after discontinuing study drug. i. Medically acceptable, highly effective forms of contraception can include approved hormonal contraceptives (oral, injectable, and implantable) and barrier methods (such as a condom or diaphragm) when used with a spermicide. Women who are successfully sterilized (including hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or postmenopausal (defined as amenorrhea for at least 12 consecutive months) are not considered to be of reproductive potential. 9. Males with a partner of childbearing potential must agree to use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug. 10. 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 (forced expiratory volume in 1 second/FVC \<0.70 at Screening) or greater extent of emphysema than fibrosis on HRCT (confirmed by central review). 3. Subject has a diagnosis of IPF. 4. 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. 5. 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), soluble guanylate cyclase stimulators, or activin signaling inhibitors (sotatercept) 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 prior to any study-related efficacy assessments. 6. Subject is receiving \>10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline. 7. Exacerbation of ILD 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 ILD or a pulmonary or upper respiratory infection, subjects must have been discharged more than 90 days prior to Baseline to be eligible. 8. Subject has uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline. 9. 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. 10. Acute pulmonary embolism within 90 days prior to Baseline. 11. 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. 12. In the opinion of the Investigator, life expectancy \<12 months due to ILD or a concomitant illness. 13. Subject has received nerandomilast within 60 days prior to Baseline.

Contacts and Locations

Sponsors and CollaboratorsUnited Therapeutics
Locations
UAB Lung Health Center | Birmingham Alabama, United States, 35233Banner University Medical Center Phoenix Lung Institute | Phoenix Arizona, United States, 85006Norton Thoracic Institute | Phoenix Arizona, United States, 85013Peter Morton Medical Building | Los Angeles California, United States, 90095NewportNativeMD, Inc. | Newport Beach California, United States, 92663University of California Irvine Medical Center | Orange California, United States, 92868Paradigm Clinical Research | Redding California, United States, 45227UC Davis Health Medical Center | Sacramento California, United States, 95817Paradigm Clinical Research | San Diego California, United States, 92108Stanford University Medical Center | Stanford California, United States, 94305Georgetown University Hospital | Washington D.C. District of Columbia, United States, 20007Ascension Medical Group St. Vincent's Lung Institute | Jacksonville Florida, United States, 32204Mayo Clinic | Jacksonville Florida, United States, 32224TGH/USF Center for Advanced Lung Disease and Lung Transplant | Tampa Florida, United States, 33606The Emory Clinic | Atlanta Georgia, United States, 45227Northwestern Memorial Hospital, Clinical Research Unit | Chicago Illinois, United States, 60611Rush University Medical Center Outpatient Pulmonary Clinic | Chicago Illinois, United States, 60612UI Health Hospital | Chicago Illinois, United States, 60612Loyola University Medical Center | Maywood Illinois, United States, 60153University of Kansas Medical Center | Kansas City Kansas, United States, 66160University of Kentucky | Lexington Kentucky, United States, 45227University of Louisville Healthcare Outpatient Research Clinic | Louisville Kentucky, United States, 40202Tulane Medical Center | New Orleans Louisiana, United States, 45227Johns Hopkins Asthma and Allergy Center | Baltimore Maryland, United States, 21224University of Maryland Medical Center | Baltimore Maryland, United States, 45227Adventist Healthcare White Oak Medical Center | Silver Spring Maryland, United States, 20904Tufts Medical Center | Boston Massachusetts, United States, 02111Massachusetts General Hospital | Boston Massachusetts, United States, 02114Infinity Medical Center | North Dartmouth Massachusetts, United States, 02747Beaumont Hospital, Royal Oak | Royal Oak Michigan, United States, 48073University of Minnesota Health Clinical Research Unit (CRU) | Minneapolis Minnesota, United States, 55455Mayo Clinic | Rochester Minnesota, United States, 55905Memorial Hospital at Gulfport | Gulfport Mississippi, United States, 39501The Lung Research Center, LLC | Chesterfield Missouri, United States, 63017Saint Luke's Hospital of Kansas City | Kansas City Missouri, United States, 64111Washington University School of Medicine | St Louis Missouri, United States, 63110University of New Mexico | Albuquerque New Mexico, United States, 87131Northwell Health | New Hyde Park New York, United States, 11042Weill Cornell Medicine, New York-Presbyterian Hospital | New York New York, United States, 10065Stony Brook Advanced Specialty Care | Stony Brook New York, United States, 11794-8172Montefiore Medical Center | The Bronx New York, United States, 10467Duke University Medical Center | Durham North Carolina, United States, 27710PulmonIx LLC | Greensboro North Carolina, United States, 27403East Carolina University | Greenville North Carolina, United States, 27834Wake Forest Baptist Health | Winston-Salem North Carolina, United States, 27104University of Cincinnati Medical Center | Cincinnati Ohio, United States, 45219The Ohio State University Wexner Medical CEnter | Columbus Ohio, United States, 43201Mercy Health St.Vincent Medical Center LLC | Toledo Ohio, United States, 43608Pennsylvania State Hershey Medical Center and College of Medicine | Hershey Pennsylvania, United States, 17033Hospital of the University of Pennsylvania | Philadelphia Pennsylvania, United States, 19104Temple University Hospital | Philadelphia Pennsylvania, United States, 19140Medical University of South Carolina-Nexus | Charleston South Carolina, United States, 29425Prisma Health Pulmonology-Richland | Columbia South Carolina, United States, 29203Clinical Trials Center of Middle Tennessee, LLC | Franklin Tennessee, United States, 37067StatCare Pulmonary Consultants, PLLC | Knoxville Tennessee, United States, 37919The Vanderbilt Lung Institute | Nashville Tennessee, United States, 37204Baylor University Medical Center | Dallas Texas, United States, 75246UT Southwestern Medical Center-Advanced Lung Clinic | Dallas Texas, United States, 75390Houston Methodist Outpatient Center | Houston Texas, United States, 77030The University of Texas Health Science Center at Houston, McGovern Medical School | Houston Texas, United States, 77030A & A Research Consultants, LLC | McAllen Texas, United States, 78503Metroplex Pulmonary and Sleep Center | McKinney Texas, United States, 75069Intermountain Medical Center | Murray Utah, United States, 84107University of Utah Health | Salt Lake City Utah, United States, 84108University of Virginia Health System | Charlottesville Virginia, United States, 22903Christopher King, MD | Falls Church Virginia, United States, 22042Pulmonary Associates of Richmond, Inc. | Richmond Virginia, United States, 23230University Hospital and UW Health Clinics | Madison Wisconsin, United States, 53792Medical College of Wisconsin | Milwaukee Wisconsin, United States, 53226-1222Instituto Ave Pulmo - Fundacion enfisema | Mar del Plata Buenos Aires, Argentina, 7600Instituto Medico Rio Cuarto | Río Cuarto Córdoba Province, Argentina, 5800Sanatorio Parque de Rosario - Consultorios Externos | Rosario Santa Fe Province, Argentina, 2000Investigaciones en Patologias Respiratorias | San Miguel de Tucumán Tucumán Province, Argentina, 4000CIMER-Centro Integral de Medicina Respiratoria | San Miguel de Tucumán Tucumán Province, Argentina, CINME Centro de Investigaciones Metabolicas | Buenos Aires , Argentina, C1056ABIFundación Respirar | Buenos Aires , Argentina, C1426ABPInstituto de Medicina Respiratoria | Córdoba , Argentina, 5003Sanatorio Allende Cerro | Córdoba , Argentina, 5021Royal Prince Alfred Hospital | Camperdown New South Wales, Australia, 2050St George Hospital | Kogarah New South Wales, Australia, 2217The Prince Charles Hospital | Brisbane Queensland, Australia, AustraliaEastern Health Box Hill Hospital | Box Hill Victoria, Australia, 3128Monash Health-Monash Medical Centre | Clayton Victoria, Australia, 3168Austin Health | Heidelberg Victoria, Australia, 3084Institute for Respiratory Health - Midland | Midland Western Australia, Australia, 6056Institute for Respiratory Health | Nedlands Western Australia, Australia, 6009AZORG | Aalst , Belgium, 9300ZAS Middelheim | Antwerp , Belgium, 2020CUB Hopital Erasmde | Brussels , Belgium, 1070Cliniques Universitaires St.-Luc | Brussels , Belgium, 1200UZ Leuven | Leuven , Belgium, 3000CHU de Liège | Liège , Belgium, 4000St.Paul's Hospital | Vancouver British Columbia, Canada, V6Z 176Dynamic Drug Advancement Limited | Ajax Ontario, Canada, L1S 2J5St.Joseph's Healthcare Hamilton | Hamilton Ontario, Canada, L8N 4A6Hôpital Maisonneuve-Rosemont | Montreal Quebec, Canada, H1T 2M4CIC Mauricie inc. | Québec Quebec, Canada, G8T 7A1Diex Recherche Inc. - Division Sherbrooke Est | Sherbrooke Quebec, Canada, J1E 0N8Centro de Investigacion Curico | Curicó Maule Region, Chile, 3341643CEC Centro Estudios Clinicos | Santiago Santiago Metropolitan, Chile, 7550495Fundacion Medica San Cristobal | Santiago Santiago Metropolitan, Chile, 7630226Biocinetic Ltda. | Santiago Santiago Metropolitan, Chile, 8320000Centro Respiratorio Integral LTDA. (CENRESIN) | Quillota Valparaiso, Chile, 2260000Centro de Investigación de Enfermedades Respiratorias e Inmunológicas (CIERI) | Viña del Mar Valparaiso, Chile, 2520000Hôpital Avicennes | Bobigny , France, 93000Hospices civils de Lyon - Hôpital Louis Pradel | Bron , France, 69500CHU Caen Normandie | Caen , France, 14000Assistance Publique Hôpitaux de Marseille - centre Hospitalier Régional de Marseille | Marseille , France, Rouen University Hospital | Rouen , France, 7600Centre Hospitalier Régional Universitaire de Tours | Tours , France, Tours Cedex 9RoMed Klinikum Rosenheim-Ellmaierstr. 23 | Rosenheim Bavaria, Germany, 83022Zentralklinik Bad Berka GmbH Klinik für Pneumologie, Zentrum für Schlaf-und Beatmungsmedizin | Bad Berka , Germany, 99437Prufstelle der GWT am Fachkrankenhaus Coswig | Coswig , Germany, 01640uhrlandklinik Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH | Essen , Germany, 45239SLK Kliniken Heilbronn GmbH | Löwenstein , Germany, 74245LMU Klinikum Medizinische Klinik und Poliklinik V | München , Germany, 81377Barzilai Medical Center | Ashkelon , Israel, 7830604Hillel Yaffe Medical Center | Hadera , Israel, 3846201Rabin Medical Center | Haifa , Israel, 3436212Shaare Zedek Medical Center | Jerusalem , Israel, 9103102The Hadassah University Medical Center Ein Kerem Hospital | Jerusalem , Israel, 9112001Meir Medical Center | Kfar Saba , Israel, 4428164Rabin Medical Center | Petah Tikva , Israel, 4941492Kaplan Medical Center | Rehovot , Israel, 7551041Tel Aviv Sourasky Medical Center | Tel Aviv , Israel, 6423906Azienda Ospedaliero Universitaria Policlinico "G. Rodolico - San Marco" Presidio Ospedaliero Gaspare Rodolico | Catania , Italy, 95123Azienda Unita Sanitaria Locale Della Romagna Ospedale "Gian Battista Morgagni - Luigi Pierantoni" di Forlì | Forlì , Italy, 47121Azienda Ospedaliero-Universitaria di Modena Policlinico di Modena | Modena , Italy, 41124Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Roma , Italy, 168Azienda Ospedaliero-Universitaria Senese | Siena , Italy, 53100Canterbury Respiratory Research Group | Christchurch Canterbury, New Zealand, 8011Aotearoa Clinical Trials Trust- Middlemore Hospital | Auckland , New Zealand, Waikato Hospital | Hamilton , New Zealand, 3204Hospital Nacional Adolfo Guevara Velasco | Cusco , Peru, 08002Clinica Internacional - Sede Lima | Lima , Peru, 15001Unidad de Investigacion de Enfermedades Respiratorias- Clinica San Pablo -Surco | Lima , Peru, 15023Clinica Ricardo Palma | Lima , Peru, 15036Hospital Central de la Fuerza Aerea del Peru | Lima , Peru, 15046Centro de Investigacion de Enfermedades Respiratorias - Clinica Providencia | Lima , Peru, 15088Gachon University Gil Medical Center | Incheon , South Korea, 21565Seoul National University Bundang Hospital | Seongnam-si , South Korea, 13620Korea University Anam Hospital | Seoul , South Korea, 02841Asan Medical Center | Seoul , South Korea, 05505The Catholic University of Korea, Eunpyeong St. Mary's Hospital | Seoul , South Korea, 3312Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung City , Taiwan, 807Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital | Kaohsiung City , Taiwan, 83301Taichung Veterans General Hospital | Taichung , Taiwan, 40705Birmingham Heartlands Hospital | Birmingham , United Kingdom, Royal Papworth Hospital | Cambridge , United Kingdom, CB2 0AYNHS Lothian, Royal INfirmary of Edingburgh | Edinburgh , United Kingdom, EH16 4SAGuy's Hospital | London , United Kingdom, SE1 9RTManchester University NHS Foundation Trust, North Manchester General Hospital | Manchester , United Kingdom, M8 5RBNHS Tayside, Perth Royal Infirmary | Perth , United Kingdom, PH1 1NX