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

NCT ID: NCT05255991

Last Updated: 2025-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 597 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-04
• Study Completion Date: 2025-06-30

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.

Detailed Description

Study RIN-PF-303 is a multinational, 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.

Conditions

Idiopathic Pulmonary Fibrosis; Interstitial Lung Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Matching placebo inhaled using an ultrasonic nebulizer QID

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo administered QID

Treprostinil Ultrasonic Nebulizer

Intervention Type: DEVICE

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

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.

Group Type: EXPERIMENTAL

Inhaled Treprostinil

Intervention Type: DRUG

Inhaled treprostinil (6 mcg/breath) administered QID

Treprostinil Ultrasonic Nebulizer

Intervention Type: DEVICE

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

Interventions

Placebo

Placebo administered QID

Intervention Type: DRUG

Inhaled Treprostinil

Inhaled treprostinil (6 mcg/breath) administered QID

Intervention Type: DRUG

Treprostinil Ultrasonic Nebulizer

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

Intervention Type: DEVICE

Other Intervention Names

Tyvaso

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CINME S.A. - Centro de Investigaciones Metabolicas

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Centro Medico Dra. De Salvo

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Instituto Ave Pulmo - Fundación enfisema

Mar del Plata, Buenos Aires, Argentina

Sanatorio Allende S.A.

Córdoba, Córdoba Province, Argentina

Instituto Médico Río Cuarto

Río Cuarto, Córdoba Province, Argentina

Centro Médico INSARES

Mendoza, Mendoza Province, Argentina

Sanatorio Parque - Consultorios Externos

Rosario, Santa Fe Province, Argentina

Centro Integral de Medicina Respiratoria

San Miguel de Tucumán, Tucumán Province, Argentina

Investigaciones en Patologías Respiratorias

San Miguel de Tucumán, Tucumán Province, Argentina

Royal Prince Alfred Hospital, Missenden Road

Camperdown, New South Wales, Australia

Macquarie University

Macquarie Park, New South Wales, Australia

Westmead Hospital, Corner of Hawkesbury and Darcy Road

Westmead, New South Wales, Australia

Cairns Hospital

Cairns, Queensland, Australia

Lung Research Qld

Chermside, Queensland, Australia

Prince Charles Hospital

Chermside, Queensland, Australia

Mater Misericordiae Ltd

South Brisbane, Queensland, Australia

Respiratory Clinical Trials Pty Ltd

Kent Town, South Australia, Australia

Alfred Health

Melbourne, Victoria, Australia

Austin Health

Melbourne, Victoria, Australia

Institute for Respiratory Health - Midland

Nedlands, Western Australia, Australia

Institute for Respiratory Health - Nedlands

Nedlands, Western Australia, Australia

Hôpital Erasme

Anderlecht, Brussels Capital, Belgium

CHU UCL Namur asbl - Site Godinne

Yvoir, Namur, Belgium

AZORG vzw

Aalst, , Belgium

Ziekenhuis Aan de Stroom

Antwerp, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

UZ Leuven

Leuven, , Belgium

CHR de la Citadelle

Liège, , Belgium

CHU de Liège

Liège, , Belgium

Centro de Investigacion del Maule SpA

Talca, Maule Region, Chile

Oncocentro APYS

Viña del Mar, Región de Valparaíso, Chile

Instituto Nacional Torax

Santiago, Santiago Metropolitan, Chile

Fundación Médica San Cristobal

Santiago, Santiago Metropolitan, Chile

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

Aarhus N, , Denmark

Gentofte Hospital - Lungemedicinsk forskning

Hellerup, , Denmark

Odense University Hospital - Department of Respiratory Medicine J.

Odense C, , Denmark

Hôpital Pontchaillou

Rennes, Ille-et-Vilaine, France

Hôpital Avicenne

Bobigny, Seine-Saint Denis, France

CHU Amiens Picardie Site Sud - Service de Pneumologie

Amiens, , France

Hopital Cote de Nacre

Caen, , France

Groupement Hospitalier EST, Service de Pneumologie

Lyon, , France

APHM-Hôpital Nord

Marseille, , France

Service de Pneumologie, Hôpital Européen Georges Pompídou (HEGP)

Paris, , France

Hôpital Bichat

Paris, , France

CHU Reims - Hôpital Maison Blanche

Reims, , France

Hôpital Charles Nicolle-1 Rue de Germont

Rouen, , France

CHU de Rouen - Hôpital Charles Nicolle

Rouen, , France

Hôpital Larrey

Toulouse, , France

CHRU Tours - Hôpital Bretonneau

Tours, , France

Klinik Löwenstein GmbH

Löwenstein, Baden-Wurttemberg, Germany

RoMed Klinikum Rosenheim

Rosenheim, Bavaria, Germany

Universitätsmedezin Essen Ruhrlandklinik Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

Essen, North Rhine-Westphalia, Germany

Zentralklinik Bad Berka GmbH

Bad Berka, , Germany

Fachkrankenhaus Coswig

Coswig, , Germany

LMU Klinikum der Universität

München, , Germany

Meir Medical Center

Kfar Saba, Central District, Israel

Kaplan Medical Center

Rehovot, Central District, Israel

Lady Davis Carmel Medical Center

Haifa, Haifa District, Israel

Shaare Zedek Medical Center

Jerusalem, Jerusalem, Israel

Hadassah Medical Center - PPDS

Jerusalem, Jerusalem, Israel

Tel Aviv Sourasky Medical Center - PPDS

Tel Aviv, Southern District, Israel

Sheba Medical Center - PPDS

Ramat Gan, Tel Aviv, Israel

Hillel Yaffe Medical Center

Hadera, , Israel

Rambam Medical Center - PPDS

Haifa, , Israel

Rabin Medical Center - PPDS

Petah Tikva, , Israel

Presidio Ospedaliero GB Morgagni L Pierantoni

Forlì, Emilia-Romagna, Italy

Ospedale S. Giuseppe Multimedica

Milan, Lombardy, Italy

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

Catania, Sicily, Italy

Azienda Ospedaliera Universitaria Senese

Siena, Tuscany, Italy

Azienda Ospedaliero-Universitaria delle Marche

Ancona, , Italy

Azienda Ospedaliero Universitaria Di Modena Policlinico

Modena, , Italy

Fondazione Policlinico Universitario A Gemelli-Rome

Roma, , Italy

Fondazione PTV Policlinico Tor Vergata

Rome, , Italy

Instituto Nacional De Enfermedades Respiratorias Ismael Cosio Villegas

Mexico City, Mexico City, Mexico

Unidad de Investigación Clínica en Medicina, S.C.

Monterrey, Nuevo León, Mexico

Hospital Universitario "Dr. José Eleuterio González"

Monterrey, Nuevo León, Mexico

Zuyderland Medisch Centrum

Heerlen, Limburg, Netherlands

Erasmus MC

Rotterdam, South Holland, Netherlands

St. Antonius Ziekenhuis

Nieuwegein, Utrecht, Netherlands

Canterbury Respiratory Research Group

Christchurch, Canterbury, New Zealand

Respiratory Medicine

Hamilton, Waikato Region, New Zealand

Hospital Nacional Adolfo Guevara Velasco

Wanchaq, Departamento de Cusco, Peru

Clinica Ricardo Palma

Lima, Lima Province, Peru

Hospital de Chancay y Servicios Basicos deSalud

Huaral, Lima region, Peru

Hospital Central de la Fuerza Aerea Del Peru

Lima, , Peru

CHA Bundang Medical Center, CHA University

Seongnam-si, Gyeonggido, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido, South Korea

Asan Medical Center

Seoul, Seoul Teugbyeolsi, South Korea

SMG - SNU Boramae Medical Center

Seoul, Seoul Teugbyeolsi, South Korea

Gachon University Gil Medical Center

Incheon, , South Korea

Korea University Anam Hospital

Seoul, , South Korea

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

Seoul, , South Korea

Samsung Medical Center - PPDS

Seoul, , South Korea

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, Spain

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, Spain

Hospital Clinic de Barcelona

Barcelona, Barcelona, Spain

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Hospital Universitario Virgen de Las Nieves

Granada, Granada, Spain

Hospital Universitario de La Princesa

Madrid, Madrid, Spain

Hospital General Universitario Gregorio Marañon

Madrid, Madrid, Spain

Hospital Clinico Universitario Virgen de la Arrixaca

Murcia, Murcia, Spain

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Hospital Clinico Universitario de Santiago

Santiago de Compostela, , Spain

Kaohsiung Medical University - Chung-Ho Memorial Hospital

Kaohsiung City, Samin District, Taiwan

E-DA hospital

Kaohsiung City, , Taiwan

Far Eastern Memorial Hospital

New Taipei City, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Countries

Argentina; Australia; Belgium; Chile; Denmark; France; Germany; Israel; Italy; Mexico; Netherlands; New Zealand; Peru; South Korea; Spain; Taiwan

Other Identifiers

2021-005881-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RIN-PF-303

Identifier Type: -

Identifier Source: org_study_id