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

NCT05255991 | Completed Phase 3 DMC FDA Drug FDA Device

• 2 other identifiers: RIN-PF-3032021-005881-17
• Study Type: interventional
• Target: 597
• Locations: 16 countries
• Sites: 108

Brief Summary

Study RIN-PF-303 is a multinational study designed to evaluate the superiority of inhaled treprostinil against placebo for the change in absolute forced vital capacity (FVC) from baseline to Week 52.

Conditions

Idiopathic Pulmonary Fibrosis; Interstitial Lung Disease

Keywords

Treprostinil; IPF; ILD

Outcome Measures

Primary Outcomes (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.

  Baseline to Week 52

Secondary Outcomes (6)

• Time to Clinical Worsening

  Baseline to Week 52

• Time to First Acute Exacerbation of IPF

  Baseline to Week 52

• Overall Survival at Week 52

  Baseline to Week 52

• Change in % Predicted FVC from Baseline to Week 52

  Baseline to Week 52

• Change in K-BILD Questionnaire Score from Baseline to Week 52

  Baseline to Week 52

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching placebo inhaled using an ultrasonic nebulizer QID

Drug: Placebo; Device: Treprostinil Ultrasonic Nebulizer

Inhaled Treprostinil

EXPERIMENTAL

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; Device: Treprostinil Ultrasonic Nebulizer

Interventions

Placebo DRUG

Placebo administered QID

Placebo

Inhaled Treprostinil DRUG

Inhaled treprostinil (6 mcg/breath) administered QID

Also known as: Tyvaso

Inhaled Treprostinil

Treprostinil Ultrasonic Nebulizer DEVICE

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

Inhaled Treprostinil; Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (108)

CINME S.A. - Centro de Investigaciones Metabolicas

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1027AAP, Argentina

Location

Centro Medico Dra. De Salvo

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1426ABP, Argentina

Location

Instituto Ave Pulmo - Fundación enfisema

Mar del Plata, Buenos Aires, 7600, Argentina

Location

Sanatorio Allende S.A.

Córdoba, Córdoba Province, 5021, Argentina

Location

Instituto Médico Río Cuarto

Río Cuarto, Córdoba Province, 5800, Argentina

Location

Centro Médico INSARES

Mendoza, Mendoza Province, 5500, Argentina

Location

Sanatorio Parque - Consultorios Externos

Rosario, Santa Fe Province, 2000, Argentina

Location

Centro Integral de Medicina Respiratoria

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Investigaciones en Patologías Respiratorias

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Royal Prince Alfred Hospital, Missenden Road

Camperdown, New South Wales, 2050, Australia

Location

Macquarie University

Macquarie Park, New South Wales, 2109, Australia

Location

Westmead Hospital, Corner of Hawkesbury and Darcy Road

Westmead, New South Wales, 2145, Australia

Location

Cairns Hospital

Cairns, Queensland, 5870, Australia

Location

Lung Research Qld

Chermside, Queensland, 4032, Australia

Location

Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Mater Misericordiae Ltd

South Brisbane, Queensland, 4101, Australia

Location

Respiratory Clinical Trials Pty Ltd

Kent Town, South Australia, 5067, Australia

Location

Alfred Health

Melbourne, Victoria, 3004, Australia

Location

Austin Health

Melbourne, Victoria, 3004, Australia

Location

Institute for Respiratory Health - Midland

Nedlands, Western Australia, 6009, Australia

Location

Institute for Respiratory Health - Nedlands

Nedlands, Western Australia, 6009, Australia

Location

Hôpital Erasme

Anderlecht, Brussels Capital, 1070, Belgium

Location

CHU UCL Namur asbl - Site Godinne

Yvoir, Namur, 5530, Belgium

Location

AZORG vzw

Aalst, 9300, Belgium

Location

Ziekenhuis Aan de Stroom

Antwerp, 2020, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHR de la Citadelle

Liège, 4000, Belgium

Location

CHU de Liège

Liège, 4000, Belgium

Location

Centro de Investigacion del Maule SpA

Talca, Maule Region, 3465586, Chile

Location

Oncocentro APYS

Viña del Mar, Región de Valparaíso, 2520598, Chile

Location

Instituto Nacional Torax

Santiago, Santiago Metropolitan, 7500691, Chile

Location

Fundación Médica San Cristobal

Santiago, Santiago Metropolitan, 7630000, Chile

Location

Aarhus University Hospital - Department of Respiratory Diseases and Allergy, Research Unit

Aarhus N, 8200, Denmark

Location

Gentofte Hospital - Lungemedicinsk forskning

Hellerup, 2900, Denmark

Location

Odense University Hospital - Department of Respiratory Medicine J.

Odense C, 5000, Denmark

Location

Hôpital Pontchaillou

Rennes, Ille-et-Vilaine, 35033, France

Location

Hôpital Avicenne

Bobigny, Seine-Saint Denis, 93000, France

Location

CHU Amiens Picardie Site Sud - Service de Pneumologie

Amiens, 80054, France

Location

Hopital Cote de Nacre

Caen, 14033, France

Location

Groupement Hospitalier EST, Service de Pneumologie

Lyon, 69677 Cedex, France

Location

APHM-Hôpital Nord

Marseille, 13015, France

Location

Service de Pneumologie, Hôpital Européen Georges Pompídou (HEGP)

Paris, 75015, France

Location

Hôpital Bichat

Paris, 75018, France

Location

CHU Reims - Hôpital Maison Blanche

Reims, 51092, France

Location

Hôpital Charles Nicolle-1 Rue de Germont

Rouen, 76000, France

Location

CHU de Rouen - Hôpital Charles Nicolle

Rouen, 76031, France

Location

Hôpital Larrey

Toulouse, 31059, France

Location

CHRU Tours - Hôpital Bretonneau

Tours, 37044, France

Location

Klinik Löwenstein GmbH

Löwenstein, Baden-Wurttemberg, 74245, Germany

Location

RoMed Klinikum Rosenheim

Rosenheim, Bavaria, 83022, Germany

Location

Universitätsmedezin Essen Ruhrlandklinik Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

Essen, North Rhine-Westphalia, 45239, Germany

Location

Zentralklinik Bad Berka GmbH

Bad Berka, 99437, Germany

Location

Fachkrankenhaus Coswig

Coswig, 01640, Germany

Location

LMU Klinikum der Universität

München, 81377, Germany

Location

Meir Medical Center

Kfar Saba, Central District, 44281, Israel

Location

Kaplan Medical Center

Rehovot, Central District, 76100, Israel

Location

Lady Davis Carmel Medical Center

Haifa, Haifa District, 34362, Israel

Location

Shaare Zedek Medical Center

Jerusalem, Jerusalem, 9103102, Israel

Location

Hadassah Medical Center - PPDS

Jerusalem, Jerusalem, 91120, Israel

Location

Tel Aviv Sourasky Medical Center - PPDS

Tel Aviv, Southern District, 64239, Israel

Location

Sheba Medical Center - PPDS

Ramat Gan, Tel Aviv, 52621, Israel

Location

Hillel Yaffe Medical Center

Hadera, 38100, Israel

Location

Rambam Medical Center - PPDS

Haifa, 3109601, Israel

Location

Rabin Medical Center - PPDS

Petah Tikva, 4910000, Israel

Location

Presidio Ospedaliero GB Morgagni L Pierantoni

Forlì, Emilia-Romagna, 47121, Italy

Location

Ospedale S. Giuseppe Multimedica

Milan, Lombardy, 20123, Italy

Location

Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco"

Catania, Sicily, 95123, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, Tuscany, 53100, Italy

Location

Azienda Ospedaliero-Universitaria delle Marche

Ancona, 60126, Italy

Location

Azienda Ospedaliero Universitaria Di Modena Policlinico

Modena, 41124, Italy

Location

Fondazione Policlinico Universitario A Gemelli-Rome

Roma, 00168, Italy

Location

Fondazione PTV Policlinico Tor Vergata

Rome, 00133, Italy

Location

Instituto Nacional De Enfermedades Respiratorias Ismael Cosio Villegas

Mexico City, Mexico City, 14080, Mexico

Location

Unidad de Investigación Clínica en Medicina, S.C.

Monterrey, Nuevo León, 64060, Mexico

Location

Hospital Universitario "Dr. José Eleuterio González"

Monterrey, Nuevo León, 64460, Mexico

Location

Zuyderland Medisch Centrum

Heerlen, Limburg, 6419 PC, Netherlands

Location

Erasmus MC

Rotterdam, South Holland, 3015 GD, Netherlands

Location

St. Antonius Ziekenhuis

Nieuwegein, Utrecht, 3435 CM, Netherlands

Location

Canterbury Respiratory Research Group

Christchurch, Canterbury, 8013, New Zealand

Location

Respiratory Medicine

Hamilton, Waikato Region, 3204, New Zealand

Location

Hospital Nacional Adolfo Guevara Velasco

Wanchaq, Departamento de Cusco, 8003, Peru

Location

Clinica Ricardo Palma

Lima, Lima Province, 15036, Peru

Location

Hospital de Chancay y Servicios Basicos deSalud

Huaral, Lima region, 15131, Peru

Location

Hospital Central de la Fuerza Aerea Del Peru

Lima, 15046, Peru

Location

CHA Bundang Medical Center, CHA University

Seongnam-si, Gyeonggido, 13496, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido, 13620, South Korea

Location

Asan Medical Center

Seoul, Seoul Teugbyeolsi, 05505, South Korea

Location

SMG - SNU Boramae Medical Center

Seoul, Seoul Teugbyeolsi, 7061, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

The Catholic University of Korea - Eunpyeong St. Mary's Hospital

Seoul, 03312, South Korea

Location

Samsung Medical Center - PPDS

Seoul, 06351, South Korea

Location

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Barcelona, 08036, Spain

Location

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Virgen de Las Nieves

Granada, Granada, 18014, Spain

Location

Hospital Universitario de La Princesa

Madrid, Madrid, 28006, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, Madrid, 28007, Spain

Location

Hospital Clinico Universitario Virgen de la Arrixaca

Murcia, Murcia, 30120, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, 15706, Spain

Location

Kaohsiung Medical University - Chung-Ho Memorial Hospital

Kaohsiung City, Samin District, 80756, Taiwan

Location

E-DA hospital

Kaohsiung City, 82445, Taiwan

Location

Far Eastern Memorial Hospital

New Taipei City, 220, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2022
• First Posted: February 25, 2022
• Study Start: October 4, 2022
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

TW (4); IL (10); PE (4); ME (3); ES (11); DE (6); KR (8); NL (3); IT (8); CL (4); BE (8); AU (12); NZ (2); FR (13); AR (9); DK (3)