Clinical trial NCT05255991: Multinational Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
Official title: A Randomized, Double-blind, Placebo-controlled, Multinational, Phase 3 Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis (TETON-2)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Interstitial Lung Disease
Keywords: Treprostinil
IPF
ILD
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-02-25
Enrollment: 597
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Absolute FVC from Baseline to Week 52
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: Time to Clinical Worsening
timeFrame: Baseline to Week 52
measure: Time to First Acute Exacerbation of IPF
timeFrame: Baseline to Week 52
measure: Overall Survival at Week 52
timeFrame: Baseline to Week 52
measure: Change in % Predicted FVC from Baseline to Week 52
timeFrame: Baseline to Week 52
measure: Change in K-BILD Questionnaire Score from Baseline to Week 52
timeFrame: Baseline to Week 52
measure: Change in DLCO from Baseline to Week 52
timeFrame: Baseline to Week 52
Other outcomes:
Locations:
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: CINME S.A. - Centro de Investigaciones Metabolicas
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Centro Medico Dra. De Salvo
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto Ave Pulmo - Fundación enfisema
state: Buenos Aires
city: Río Cuarto
country: Argentina
facility: Instituto Médico Río Cuarto
state: Cordoba
city: Rosario
country: Argentina
facility: Sanatorio Parque - Consultorios Externos
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Centro Integral de Medicina Respiratoria
state: Tucuman
city: San Miguel de Tucuman
country: Argentina
facility: Investigaciones en Patologías Respiratorias
state: Tucuman
city: Cordoba
country: Argentina
facility: Sanatorio Allende S.A.
city: Mendoza
country: Argentina
facility: Centro Médico INSARES
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital, Missenden Road
state: New South Wales
city: Macquarie Park
country: Australia
facility: Macquarie University
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital, Corner of Hawkesbury and Darcy Road
state: New South Wales
city: Cairns
country: Australia
facility: Cairns Hospital
state: Queensland
city: Chermside
country: Australia
facility: Lung Research Qld
state: Queensland
city: Chermside
country: Australia
facility: Prince Charles Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd
state: Queensland
city: Kent Town
country: Australia
facility: Respiratory Clinical Trials Pty Ltd
state: South Australia
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Melbourne
country: Australia
facility: Austin Health
state: Victoria
city: Nedlands
country: Australia
facility: Institute for Respiratory Health - Midland
state: Western Australia
city: Nedlands
country: Australia
facility: Institute for Respiratory Health - Nedlands
state: Western Australia
city: Anderlecht
country: Belgium
facility: Hôpital Erasme
state: Brussels
city: Yvoir
country: Belgium
facility: CHU UCL Namur asbl - Site Godinne
state: Namur
city: Aalst
country: Belgium
facility: AZORG vzw
city: Antwerpen
country: Belgium
facility: Ziekenhuis Aan de Stroom
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHR de la Citadelle
city: Liège
country: Belgium
facility: CHU de Liège
city: Talca
country: Chile
facility: Centro de Investigacion del Maule SpA
state: Maule
city: Santiago
country: Chile
facility: Fundación Médica San Cristobal
state: Region Metropolitana
city: Santiago
country: Chile
facility: Instituto Nacional Torax
state: Región Metropolitana
city: Viña del Mar
country: Chile
facility: Oncocentro APYS
state: Valparaiso
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital - Department of Respiratory Diseases and Allergy, Research Unit
city: Hellerup
country: Denmark
facility: Gentofte Hospital - Lungemedicinsk forskning
city: Odense C
country: Denmark
facility: Odense University Hospital - Department of Respiratory Medicine J.
city: Rennes
country: France
facility: Hôpital Pontchaillou
state: Ille-et-Vilaine
city: Bobigny
country: France
facility: Hôpital Avicenne
state: Seine-Saint Denis
city: Amiens Cedex 1
country: France
facility: CHU Amiens Picardie Site Sud - Service de Pneumologie
city: Caen
country: France
facility: Hopital Cote de Nacre
city: Lyon
country: France
facility: Groupement Hospitalier EST, Service de Pneumologie
city: Marseille
country: France
facility: APHM-Hôpital Nord
city: Paris
country: France
facility: Service de Pneumologie, Hôpital Européen Georges Pompídou (HEGP)
city: Paris
country: France
facility: Hôpital Bichat
city: Reims Cedex
country: France
facility: CHU Reims - Hôpital Maison Blanche
city: Rouen cedex
country: France
facility: CHU de Rouen - Hôpital Charles Nicolle
city: Rouen
country: France
facility: Hôpital Charles Nicolle-1 Rue de Germont
city: Toulouse Cedex 9
country: France
facility: Hôpital Larrey
city: TOURS Cedex 9
country: France
facility: CHRU Tours - Hôpital Bretonneau
city: Löwenstein
country: Germany
facility: Klinik Löwenstein GmbH
state: Baden-Württemberg
city: Rosenheim
country: Germany
facility: RoMed Klinikum Rosenheim
state: Bayern
city: Essen
country: Germany
facility: Universitätsmedezin Essen Ruhrlandklinik Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
state: Nordrhein-Westfalen
city: Bad Berka
country: Germany
facility: Zentralklinik Bad Berka GmbH
city: Coswig
country: Germany
facility: Fachkrankenhaus Coswig
city: München
country: Germany
facility: LMU Klinikum der Universität
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center - PPDS
state: HaDarom
city: Kfar Sava
country: Israel
facility: Meir Medical Center
state: HaMerkaz
city: Rehovot
country: Israel
facility: Kaplan Medical Center
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: Sheba Medical Center - PPDS
state: Tel-Aviv
city: Ramat-Gan
country: Israel
facility: Sheba Medical Center - PPDS
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
state: Yerushalayim
city: Jerusalem
country: Israel
facility: Hadassah Medical Center - PPDS
state: Yerushalayim
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center - PPDS
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Petah Tiqva
country: Israel
facility: Rabin Medical Center - PPDS
city: Forli
country: Italy
facility: Presidio Ospedaliero GB Morgagni L Pierantoni
state: Emilia-Romagna
city: Milano
country: Italy
facility: Ospedale S. Giuseppe Multimedica
state: Lombardia
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco"
state: Sicilia
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
state: Toscana
city: Ancona
country: Italy
facility: Azienda Ospedaliero-Universitaria delle Marche
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Di Modena Policlinico
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli-Rome
city: Rome
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
state: Gyeonggido
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: SMG - SNU Boramae Medical Center
state: Seoul Teugbyeolsi
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea - Eunpyeong St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center - PPDS
city: Monterrey
country: Mexico
facility: Unidad de Investigación Clínica en Medicina, S.C.
state: Nuevo León
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. José Eleuterio González"
state: Nuevo León
city: Ciudad de México
country: Mexico
facility: Instituto Nacional De Enfermedades Respiratorias Ismael Cosio Villegas
city: Heerlen
country: Netherlands
facility: Zuyderland Medisch Centrum
state: Limburg
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
state: Utrecht
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
city: Christchurch
country: New Zealand
facility: Canterbury Respiratory Research Group
state: Canterbury
city: Hamilton
country: New Zealand
facility: Respiratory Medicine
state: Waikato
city: Wanchaq
country: Peru
facility: Hospital Nacional Adolfo Guevara Velasco
state: Cusco
city: Huaral
country: Peru
facility: Hospital de Chancay y Servicios Basicos deSalud
state: Lima
city: Lima
country: Peru
facility: Clinica Ricardo Palma
city: Lima
country: Peru
facility: Hospital Central de la Fuerza Aerea Del Peru
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Islas Baleares
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Granada
country: Spain
facility: Hospital Universitario Virgen de Las Nieves
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Murcia
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University - Chung-Ho Memorial Hospital
state: Samin District
city: Kaohsiung
country: Taiwan
facility: E-DA hospital
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
References: