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

Idiopathic Pulmonary Fibrosis Clinical Trial

— TETON-2  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05255991
• Other study ID #: RIN-PF-303
• Secondary ID: 2021-005881-17
• Status: Recruiting
• Phase: Phase 3
• Start date: October 4, 2022
• Est. completion date: June 2025

Study information

• Verified date: May 2024
• Source: United Therapeutics
• Contact: United Therapeutics Global Medical Information
• Phone: 919-485-8350
• Email: clinicaltrials[@]unither.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 576
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Interstitial Lung Disease
• Lung Diseases
• Lung Diseases, Interstitial
• Pulmonary Fibrosis

Intervention

Drug:
• Placebo
Placebo administered QID
• Inhaled Treprostinil
Inhaled treprostinil (6 mcg/breath) administered QID

Device:
• Treprostinil Ultrasonic Nebulizer
Treprostinil ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.

Locations

Country	Name	City	State
Argentina	Centro Medico Dra. De Salvo	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	CINME S.A. - Centro de Investigaciones Metabolicas	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Sanatorio Allende S.A.	Cordoba
Argentina	Instituto Ave Pulmo - Fundación enfisema	Mar del Plata	Buenos Aires
Argentina	Centro Médico INSARES	Mendoza
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
Australia	Cairns Hospital	Cairns	Queensland
Australia	Royal Prince Alfred Hospital, Missenden Road	Camperdown	New South Wales
Australia	Lung Research Qld	Chermside	Queensland
Australia	Prince Charles Hospital	Chermside	Queensland
Australia	Respiratory Clinical Trials Pty Ltd	Kent Town	South Australia
Australia	Macquarie University	Macquarie Park	New South Wales
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	Mater Misericordiae Ltd	South Brisbane	Queensland
Australia	Westmead Hospital, Corner of Hawkesbury and Darcy Road	Westmead	New South Wales
Belgium	Onze-Lieve-Vrouwziekenhuis -Aalst	Aalst
Belgium	Hôpital Erasme	Anderlecht	Brussels
Belgium	Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim	Antwerpen
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	UZ Leuven	Leuven
Belgium	CHR de la Citadelle	Liège
Belgium	CHU de Liège	Liège
Belgium	CHU UCL Namur asbl - Site Godinne	Yvoir	Namur
Chile	Fundación Médica San Cristobal	Santiago	Region Metropolitana
Chile	Instituto Nacional Torax	Santiago	Región Metropolitana
Chile	Centro de Investigacion del Maule SpA	Talca	Maule
Chile	Oncocentro APYS	Viña del Mar	Valparaiso
Denmark	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
France	CHU Amiens Picardie Site Sud - Service de Pneumologie	Amiens Cedex 1
France	Hôpital Avicenne	Bobigny	Seine-Saint Denis
France	Hopital Cote de Nacre	Caen
France	Groupement Hospitalier EST, Service de Pneumologie	Lyon
France	APHM-Hôpital Nord	Marseille
France	Hôpital Bichat	Paris
France	Service de Pneumologie, Hôpital Européen Georges Pompídou (HEGP)	Paris
France	CHU Reims - Hôpital Maison Blanche	Reims Cedex
France	Hôpital Pontchaillou	Rennes	Ille-et-Vilaine
France	Hôpital Charles Nicolle-1 Rue de Germont	Rouen
France	Hôpital Larrey	Toulouse Cedex 9
France	CHRU Tours - Hôpital Bretonneau	TOURS Cedex 9
Germany	Zentralklinik Bad Berka GmbH	Bad Berka
Germany	Fachkrankenhaus Coswig	Coswig
Germany	Universitätsmedezin Essen Ruhrlandklinik Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH	Essen	Nordrhein-Westfalen
Germany	Klinik Löwenstein GmbH	Löwenstein	Baden-Württemberg
Germany	LMU Klinikum der Universität	München
Germany	RoMed Klinikum Rosenheim	Rosenheim	Bayern
Israel	Hillel Yaffe Medical Center	Hadera
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Rambam Medical Center - PPDS	Haifa
Israel	Hadassah Medical Center - PPDS	Jerusalem	Yerushalayim
Israel	Shaare Zedek Medical Center	Jerusalem	Yerushalayim
Israel	Meir Medical Center	Kfar Sava	HaMerkaz
Israel	Rabin Medical Center - PPDS	Petah Tiqva
Israel	Sheba Medical Center - PPDS	Ramat Gan	Tel-Aviv
Israel	Sheba Medical Center - PPDS	Ramat-Gan	Tel-Aviv
Israel	Kaplan Medical Center	Rehovot	HaMerkaz
Israel	Tel Aviv Sourasky Medical Center - PPDS	Tel Aviv	HaDarom
Italy	Azienda Ospedaliero-Universitaria delle Marche	Ancona
Italy	Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco"	Catania	Sicilia
Italy	Presidio Ospedaliero GB Morgagni L Pierantoni	Forli	Emilia-Romagna
Italy	Ospedale S. Giuseppe Multimedica	Milano	Lombardia
Italy	Azienda Ospedaliero Universitaria Di Modena Policlinico	Modena
Italy	Fondazione Policlinico Universitario A Gemelli-Rome	Roma
Italy	Fondazione PTV Policlinico Tor Vergata	Rome
Italy	Azienda Ospedaliera Universitaria Senese	Siena	Toscana
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	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	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	SMG - SNU Boramae Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	The Catholic University of Korea - Eunpyeong St. Mary's Hospital	Seoul
Mexico	Instituto Nacional De Enfermedades Respiratorias Ismael Cosio Villegas	Ciudad de México
Mexico	Hospital Universitario "Dr. José Eleuterio González"	Monterrey	Nuevo León
Mexico	Unidad de Investigación Clínica en Medicina, S.C.	Monterrey	Nuevo León
Netherlands	Zuyderland Medisch Centrum	Heerlen	Limburg
Netherlands	St. Antonius Ziekenhuis	Nieuwegein	Utrecht
Netherlands	Erasmus MC	Rotterdam	Zuid-Holland
New Zealand	Canterbury Respiratory Research Group	Christchurch	Canterbury
New Zealand	Respiratory Medicine	Hamilton	Waikato
Peru	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	Hospital Nacional Adolfo Guevara Velasco	Wanchaq	Cusco
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Virgen de Las Nieves	Granada
Spain	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Clinico Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Hospital Universitario Son Espases	Palma De Mallorca	Islas Baleares
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela
Taiwan	E-DA hospital	Kaohsiung
Taiwan	Kaohsiung Medical University - Chung-Ho Memorial Hospital	Kaohsiung	Samin District
Taiwan	Far Eastern Memorial Hospital	New Taipei City
Taiwan	Taipei Veterans General Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Countries where clinical trial is conducted

Argentina,  Australia,  Belgium,  Chile,  Denmark,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Peru,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to Clinical Worsening	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.	Baseline to Week 52
Secondary	Time to First Acute Exacerbation of IPF	An exacerbation of IPF is defined as an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality.	Baseline to Week 52
Secondary	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.	Baseline to Week 52
Secondary	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 ethnicity, sex, age, height, and weight.	Baseline to Week 52
Secondary	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 interstitial lung disease (ILD) consisting of 3 domains (breathlessness and activities, psychological, and chest symptoms).	Baseline to Week 52
Secondary	Change in DLCO from Baseline to Week 52	The DLCO measurement measures how well oxygen moves from the lungs to the blood.	Baseline to Week 52