Multinational Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
- Conditions
- Interstitial Lung DiseaseIdiopathic Pulmonary Fibrosis
- Interventions
- Registration Number
- NCT05255991
- Lead Sponsor
- United Therapeutics
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 597
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Matching placebo inhaled using an ultrasonic nebulizer QID Placebo Treprostinil Ultrasonic Nebulizer Matching placebo inhaled using an ultrasonic nebulizer QID Inhaled Treprostinil Treprostinil Ultrasonic Nebulizer 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. Inhaled Treprostinil 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.
- Primary Outcome Measures
Name Time Method Change in Absolute FVC from Baseline to Week 52 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
Name Time Method Time to First Acute Exacerbation of IPF Baseline to Week 52 An exacerbation of IPF is defined as an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality.
Change in % Predicted FVC from Baseline to Week 52 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.
Overall Survival at Week 52 Baseline to Week 52 Vital status will be assessed for all subjects at Week 52, including those who discontinue the study prematurely or who withdraw consent.
Time to Clinical Worsening Baseline to Week 52 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.
Change in K-BILD Questionnaire Score from Baseline to Week 52 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).
Change in DLCO from Baseline to Week 52 Baseline to Week 52 The DLCO measurement measures how well oxygen moves from the lungs to the blood.
Trial Locations
- Locations (108)
Hospital de Chancay y Servicios Basicos deSalud
🇵🇪Huaral, Lima, Peru
Clinica Ricardo Palma
🇵🇪Lima, Peru
Hospital Central de la Fuerza Aerea Del Peru
🇵🇪Lima, Peru
Sanatorio Allende S.A.
🇦🇷Cordoba, Argentina
Centro Médico INSARES
🇦🇷Mendoza, Argentina
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
Instituto Médico Río Cuarto
🇦🇷Río Cuarto, Cordoba, Argentina
Sanatorio Parque - Consultorios Externos
🇦🇷Rosario, Santa Fe, Argentina
Centro Integral de Medicina Respiratoria
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
Investigaciones en Patologías Respiratorias
🇦🇷San Miguel de Tucuman, Tucuman, 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, Belgium
CHU UCL Namur asbl - Site Godinne
🇧🇪Yvoir, Namur, Belgium
AZORG vzw
🇧🇪Aalst, Belgium
Ziekenhuis Aan de Stroom
🇧🇪Antwerpen, 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, Chile
Fundación Médica San Cristobal
🇨🇱Santiago, Region Metropolitana, Chile
Instituto Nacional Torax
🇨🇱Santiago, Región Metropolitana, Chile
Oncocentro APYS
🇨🇱Viña del Mar, Valparaiso, 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 Cedex 1, 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 Cedex, France
CHU de Rouen - Hôpital Charles Nicolle
🇫🇷Rouen cedex, France
Hôpital Charles Nicolle-1 Rue de Germont
🇫🇷Rouen, France
Hôpital Larrey
🇫🇷Toulouse Cedex 9, France
CHRU Tours - Hôpital Bretonneau
🇫🇷TOURS Cedex 9, France
Klinik Löwenstein GmbH
🇩🇪Löwenstein, Baden-Württemberg, Germany
RoMed Klinikum Rosenheim
🇩🇪Rosenheim, Bayern, Germany
Universitätsmedezin Essen Ruhrlandklinik Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
🇩🇪Essen, Nordrhein-Westfalen, Germany
Zentralklinik Bad Berka GmbH
🇩🇪Bad Berka, Germany
Fachkrankenhaus Coswig
🇩🇪Coswig, Germany
LMU Klinikum der Universität
🇩🇪München, Germany
Tel Aviv Sourasky Medical Center - PPDS
🇮🇱Tel Aviv, HaDarom, Israel
Meir Medical Center
🇮🇱Kfar Sava, HaMerkaz, Israel
Kaplan Medical Center
🇮🇱Rehovot, HaMerkaz, Israel
Sheba Medical Center - PPDS
🇮🇱Ramat-Gan, Tel-Aviv, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Yerushalayim, Israel
Hadassah Medical Center - PPDS
🇮🇱Jerusalem, Yerushalayim, Israel
Hillel Yaffe Medical Center
🇮🇱Hadera, Israel
Rambam Medical Center - PPDS
🇮🇱Haifa, Israel
Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Rabin Medical Center - PPDS
🇮🇱Petah Tiqva, Israel
Presidio Ospedaliero GB Morgagni L Pierantoni
🇮🇹Forli, Emilia-Romagna, Italy
Ospedale S. Giuseppe Multimedica
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco"
🇮🇹Catania, Sicilia, Italy
Azienda Ospedaliera Universitaria Senese
🇮🇹Siena, Toscana, 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
CHA Bundang Medical Center, CHA University
🇰🇷Seongnam-si, Gyeonggido, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggido, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
SMG - SNU Boramae Medical Center
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea - Eunpyeong St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center - PPDS
🇰🇷Seoul, Korea, Republic of
Unidad de Investigación Clínica en Medicina, S.C.
🇲🇽Monterrey, Nuevo León, Mexico
Hospital Universitario "Dr. José Eleuterio González"
🇲🇽Monterrey, Nuevo León, Mexico
Instituto Nacional De Enfermedades Respiratorias Ismael Cosio Villegas
🇲🇽Ciudad de México, Mexico
Zuyderland Medisch Centrum
🇳🇱Heerlen, Limburg, Netherlands
St. Antonius Ziekenhuis
🇳🇱Nieuwegein, Utrecht, Netherlands
Erasmus MC
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Canterbury Respiratory Research Group
🇳🇿Christchurch, Canterbury, New Zealand
Respiratory Medicine
🇳🇿Hamilton, Waikato, New Zealand
Hospital Nacional Adolfo Guevara Velasco
🇵🇪Wanchaq, Cusco, Peru
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Hospital Universitario de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Son Espases
🇪🇸Palma De Mallorca, Islas Baleares, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Virgen de Las Nieves
🇪🇸Granada, Spain
Hospital Universitario de La Princesa
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Hospital Clinico Universitario de Santiago
🇪🇸Santiago de Compostela, Spain
Kaohsiung Medical University - Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Samin District, Taiwan
E-DA hospital
🇨🇳Kaohsiung, Taiwan
Far Eastern Memorial Hospital
🇨🇳New Taipei City, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan