Clinical trial • Phase III • Respiratory

TREPROSTINIL for Progressive pulmonary fibrosis | Pulmonary fibrosis

Phase III trial of TREPROSTINIL for Progressive pulmonary fibrosis | Pulmonary fibrosis.

Overview

Trial Therapeutic Area
Respiratory
Trial Disease
Progressive pulmonary fibrosis | Pulmonary fibrosis
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
08-11-2024
First CTIS Authorization Date
17-03-2025

Trial design

Randomised, placebo nebuliser solution identical to treprostinil nebuliser solution except for the absence of the treprostinil drug substance; (active arm: inhaled treprostinil nebuliser solution). dose/schedule details not specified in the provided part i excerpt.-controlled Phase III trial across 41 sites in France, Germany, Italy and others.

Randomised
Yes
Comparator
Placebo nebuliser solution identical to Treprostinil Nebuliser Solution except for the absence of the treprostinil drug substance; (active arm: inhaled Treprostinil nebuliser solution). Dose/schedule details not specified in the provided Part I excerpt.
Target Sample Size
483
Trial Duration For Participant
364

Eligibility

Recruits 483 Vulnerable population selected. Consent: 'Subject gives voluntary informed consent to participate in the study.' Subjects must be ≥18 years of age at the time of signing informed consent. Subject information and informed consent form documents (L1) are provided in multiple country/language versions (examples in the document list: German, French, Italian, Spanish, Dutch, English)..

Pregnancy Exclusion
Subject is pregnant or lactating.
Vulnerable Population
Vulnerable population selected. Consent: 'Subject gives voluntary informed consent to participate in the study.' Subjects must be ≥18 years of age at the time of signing informed consent. Subject information and informed consent form documents (L1) are provided in multiple country/language versions (examples in the document list: German, French, Italian, Spanish, Dutch, English).

Inclusion criteria

  • {"criterion_text":"- Subject gives voluntary informed consent to participate in the study."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- Subject is ≥18 years of age, inclusive, at the time of signing informed consent."}
  • {"criterion_text":"- Subject has radiological evidence of pulmonary fibrosis of >10% extent on an HRCT scan in the previous 12 months (confirmed by central review)."}
  • {"criterion_text":"- Subject has a diagnosis of PPF (other than IPF) that fulfills at least 1 of the following criteria for progression within 24 months of screening despite standard treatment of ILD, as assessed by the Investigator: a) Clinically significant decline in % predicted FVC based on ≥10% relative decline b) Marginal decline in % predicted FVC based on ≥5% to <10% relative decline combined with worsening of respiratory symptoms c) Marginal decline in % predicted FVC based on ≥5% to <10% relative decline combined with increasing extent of fibrotic changes on chest imaging d) Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging"}
  • {"criterion_text":"- FVC ≥45% predicted at Screening (confirmed by central review)."}
  • {"criterion_text":"- Subjects must be on 1 of the following: a) On nintedanib or pirfenidone for ≥90 days prior to Baseline and in the Investigator’s opinion, are planning to continue treatment through the study b) Not on treatment with nintedanib or pirfenidone for ≥90 days prior to Baseline and in the Investigator’s opinion, not planning to initiate either treatment during the study. Concomitant use of both nintedanib and pirfenidone is not permitted."}
  • {"criterion_text":"- Subjects treated with immunosuppressive agents (eg, mycophenolate, methotrexate, azathioprine, oral corticosteroids, rituximab) need to be on treatment for at least 120 days prior to Baseline and, in the Investigator’s clinical opinion, must be refractory to treatment."}
  • {"criterion_text":"- Women of childbearing potential must be nonpregnant (as confirmed by a urine pregnancy test at Screening and Baseline) and nonlactating, and will agree to do 1 of the following: a) Abstain from intercourse (when it is in line with their preferred and usual lifestyle) b) Use 2 medically acceptable, highly effective forms of contraception for the duration of the study, and at least 30 days after discontinuing study drug. 1)Medically acceptable, highly effective forms of contraception can include approved hormonal contraceptives (oral, injectable, and implantable) and barrier methods (such as a condom or diaphragm) when used with a spermicide. Women who are successfully sterilized (including hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or postmenopausal (defined as amenorrhea for at least 12 consecutive months) are not considered to be of reproductive potential."}
  • {"criterion_text":"- Males with a partner of childbearing potential must agree to use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug."}

Exclusion criteria

  • {"criterion_text":"- Subject is pregnant or lactating."}
  • {"criterion_text":"- Exacerbation of ILD 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 ILD or a pulmonary or upper respiratory infection, subjects must have been discharged more than 90 days prior to Baseline to be eligible."}
  • {"criterion_text":"- Subject has uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline."}
  • {"criterion_text":"- 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 noninterventional, observational, or registry studies are eligible."}
  • {"criterion_text":"- Subject has received nerandomilast within 60 days prior to Baseline."}
  • {"criterion_text":"- Acute pulmonary embolism within 90 days prior to Baseline."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- In the opinion of the Investigator, life expectancy <12 months due to ILD or a concomitant illness."}
  • {"criterion_text":"- Subject has primary obstructive airway physiology (forced expiratory volume in 1 second/FVC <0.70 at Screening) or greater extent of emphysema than fibrosis on HRCT (confirmed by central review)."}
  • {"criterion_text":"- Subject has a diagnosis of IPF."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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 (PDE5Is), soluble guanylate cyclase stimulators , or activin signaling inhibitors (sotatercept) within 60 days prior to Baseline. As needed use of a PDE5I for erectile dysfunction is permitted, provided no doses are taken within 48 hours prior to any studyrelated efficacy assessments."}
  • {"criterion_text":"- Subject is receiving >10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change in absolute FVC from baseline to Week 52.","definition_or_measurement_approach":"Absolute change in FVC from baseline to Week 52 measured by spirometry. Central read/central training for spirometry is indicated in sponsor third-party duties ('Surrogate endpoint test - Central Read of Spirometry and Training sites on 2019ATS guidelines')."}

Secondary endpoints

  • {"endpoint_text":"- Time to first clinical worsening event (including time to death, respiratory hospitalization, or ≥10% relative decline in % predicted FVC)","definition_or_measurement_approach":"Time-to-event measured from randomisation to first occurrence of death, respiratory hospitalization, or ≥10% relative decline in % predicted FVC."}
  • {"endpoint_text":"- Time to first acute exacerbation of ILD","definition_or_measurement_approach":"Time-to-event measured from randomisation to first adjudicated acute exacerbation of ILD."}
  • {"endpoint_text":"- Overall survival at Week 52","definition_or_measurement_approach":"Vital status assessed up to Week 52."}
  • {"endpoint_text":"- Change from baseline in % predicted FVC at Week 52","definition_or_measurement_approach":"Change in percent predicted FVC from baseline to Week 52 measured by spirometry."}
  • {"endpoint_text":"- Change from baseline in K-BILD score at Week 52","definition_or_measurement_approach":"Change in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) score from baseline to Week 52."}
  • {"endpoint_text":"- Change from baseline in DLCO at Week 52","definition_or_measurement_approach":"Change in diffusion capacity of lungs for carbon monoxide (DLCO) from baseline to Week 52."}
  • {"endpoint_text":"- Change from baseline in absolute FVC at Weeks 16, 28, and 40","definition_or_measurement_approach":"Change in absolute FVC from baseline measured at Weeks 16, 28 and 40 by spirometry."}
  • {"endpoint_text":"- Change from baseline in NT-proBNP at Week 52","definition_or_measurement_approach":"Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration from baseline to Week 52 (laboratory assay)."}
  • {"endpoint_text":"- Change from baseline in resting supplemental oxygen use at Week 52","definition_or_measurement_approach":"Change in resting supplemental oxygen usage from baseline to Week 52 (recorded oxygen flow and mode)."}
  • {"endpoint_text":"- AEs and serious adverse events (SAEs)","definition_or_measurement_approach":"Adverse events and serious adverse events collected and reported per standard safety reporting procedures."}
  • {"endpoint_text":"- Clinical laboratory parameters","definition_or_measurement_approach":"Clinical laboratory tests (hematology, biochemistry, as specified in protocol) monitored over study duration."}
  • {"endpoint_text":"- Vital signs, including saturation of peripheral capillary oxygenation (SpO2)","definition_or_measurement_approach":"Vital signs assessed at study visits; SpO2 measured by pulse oximetry."}
  • {"endpoint_text":"- 12-Lead electrocardiograms","definition_or_measurement_approach":"12-lead ECGs performed per schedule to assess cardiac safety."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
483
Recruitment Window Months
29
Consent Approach
Informed consent obtained from each subject: 'Subject gives voluntary informed consent to participate in the study.' Subjects must be ≥18 years at time of consent. Main ICF (L1) and country-specific ICFs are provided (documents L1 listed in multiple languages: German, French, Italian, Spanish, Dutch, English, etc.). A pregnancy follow-up ICF and privacy/reimbursement ICFs are also listed for specific countries.

Methods

  • Country-specific recruitment arrangements documents (K1) describing recruitment and informed consent procedures (documents present for FRA, DEU, ITA, ESP, BE).
  • Recruitment brochures (K2_Recruitment_Brochure) — patient-facing brochures available in country-specific language versions (France, Germany, Italy, Spain, Belgium).
  • PPF-Symposium video materials (K2_PPF-Symposium Video) with scripts and screenshots provided (country/language-specific video scripts and screenshots listed).

Geography

Total Number Of Sites
41
Total Number Of Participants
242

France

Earliest CTIS Part Ii Submission Date
07-02-2025
Latest Decision Or Authorization Date
20-04-2026
Processing Time Days
437
Number Of Sites
7
Number Of Participants
40

Sites

Site Name
Hospices Civils De Lyon
Department Name
Pneumologie
Contact Person Name
Vincent COTTIN
Contact Person Email
vincent.cottin@chu-lyon.fr
Site Name
Centre Hospitalier Universitaire De Caen Normandie
Department Name
Pneumologie
Contact Person Name
Emmanuel BERGOT
Contact Person Email
bergot-e@chu-caen.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Maladies Pulmonaires
Contact Person Name
Martine REYNAUD-GAUBERT
Contact Person Email
martinelouise.reynaud@ap-hm.fr
Site Name
Centre Hospitalier Universitaire Rouen
Department Name
Pneumologie
Contact Person Name
Mathieu SALAUN
Contact Person Email
mathieu.salaun@chu-rouen.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Pneumologie
Contact Person Name
Hilario NUNES
Contact Person Email
hilario.nunes@aphp.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Pneumologie
Contact Person Name
Julie MANKIKIAN
Contact Person Email
j.mankikian@chu-tours.fr

Germany

Earliest CTIS Part Ii Submission Date
27-01-2025
Latest Decision Or Authorization Date
15-04-2026
Processing Time Days
443
Number Of Sites
11
Number Of Participants
55

Sites

Site Name
SLK-Kliniken Heilbronn GmbH
Department Name
Klinik für Pneumologie, Intensiv- und Beatmungsmedizin
Contact Person Name
Jonas Kuon
Contact Person Email
jonas.kuon@slk-kliniken.de
Site Name
Medizinische Hochschule Hannover
Department Name
Medizinische Hochschule Hannover
Contact Person Name
Jonas Schupp
Contact Person Email
schupp.jonas@mh-hannover.de
Site Name
Romed Klinikum Rosenheim
Department Name
Medizinische Klinik III
Contact Person Name
Stephan Budweiser
Contact Person Email
stephan.budweiser@ro-med.de
Site Name
Justus-Liebig-Universitaet Giessen
Department Name
Zentrum für Interstitielle und seltene Lungenerkrankungen
Contact Person Name
Andreas Günther
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Zentrum für Onkologie, Studienzentrale Pneumologie
Contact Person Name
Tim Oqueka
Contact Person Email
t.oqueka@uke.de
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Medizinische Klinik und Poliklinik V
Contact Person Name
Jürgen Behr
Site Name
Ruhrlandklinik Westdeutsches Lungenzentrum Am Universitaetsklinikum Essen gGmbH
Department Name
Ruhrlandklinik - Westdeutsches Lungenzentrum
Contact Person Name
Francesco Tommaso Bonella
Site Name
Thoraxzentrum Bezirk Unterfranken
Department Name
Thoraxzentrum Bezirk Unterfranken
Contact Person Name
Bernd Seese
Contact Person Email
b.seese@tzbu.de
Site Name
GWT-Tud GmbH
Department Name
Prüfstelle der GWT
Contact Person Name
Dirk Koschel
Site Name
Zentralklinik Bad Berka GmbH
Department Name
Klinik für Pneumologie, Zentrum für Schlaf- und Beatmungsmedizin
Contact Person Name
Michael Weber
Contact Person Email
michael.weber@zentralklinik.de
Site Name
Lungenfachklinik Immenhausen
Department Name
Lungenfachklinik Immenhausen
Contact Person Name
Peter Hammerl

Italy

Earliest CTIS Part Ii Submission Date
13-02-2025
Latest Decision Or Authorization Date
20-04-2026
Processing Time Days
431
Number Of Sites
8
Number Of Participants
51

Sites

Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
S.C. Pneumologia
Contact Person Name
Fabrizio Luppi
Contact Person Email
fabrizio.luppi@unimib.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
Department Name
U.O.C. di Pneumologia
Contact Person Name
Carlo Vancheri
Contact Person Email
vancheri@unict.it
Site Name
Azienda Ospedaliera Universitaria Senese
Department Name
Dipartimento di Scienze Mediche - UOC Malattie dell’Apparato Respiratorio e Trapianto Polmonare
Contact Person Name
Elena Bargagli
Contact Person Email
bargagli2@gmail.com
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
S.C. Pneumologia
Contact Person Name
Claudia Ravaglia
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
U.O.C di Pneumologia
Contact Person Name
Giacomo Sgalla
Site Name
Azienda Ospedaliero Universitaria Delle Marche
Department Name
Patologie Polmonari Infiltrative Diffuse, Pleuriche e delle Bronchiectesie dell'Adulto
Contact Person Name
Federico Mei
Site Name
Centro Ricerche Cliniche Di Verona S.r.l.
Department Name
Pneumology Unit
Contact Person Name
Claudio Micheletto
Site Name
Azienda Ospedaliero Universitaria Di Modena
Department Name
Clinica Malattie Apparato Respiratorio
Contact Person Name
Stefania Cerri
Contact Person Email
stefania.cerri@unimore.it

Spain

Earliest CTIS Part Ii Submission Date
10-01-2025
Latest Decision Or Authorization Date
17-04-2026
Processing Time Days
462
Number Of Sites
7
Number Of Participants
45

Sites

Site Name
Bellvitge University Hospital
Department Name
Neumology
Contact Person Name
Maria Molina Molina
Contact Person Email
mariamolinamolina@hotmail.com
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Neumology
Contact Person Name
Luis Puente-Maestu
Contact Person Email
lpuente@separ.es
Site Name
Hospital Universitari Vall D Hebron
Department Name
Neumology
Contact Person Name
Ana Villar Gomez
Contact Person Email
ana.villar@vallhebron.cat
Site Name
Hospital Universitario Marques De Valdecilla
Department Name
Neumology
Contact Person Name
Jose Manuel Cifrian Martinez
Contact Person Email
josemanuel.cifrian@scsalud.es
Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Neumology
Contact Person Name
Juan Suarez Antelo
Contact Person Email
juan.suarez.antelo@sergas.es
Site Name
Hospital Universitario Virgen De La Victoria
Department Name
Neumology
Contact Person Name
Jose Velasco Garrido
Contact Person Email
jlvelascogarrido@hotmail.com
Site Name
University Clinical Hospital Virgen De La Arrixaca
Department Name
Neumology
Contact Person Name
Jose Antonio Ros-Lucas
Contact Person Email
sleepfq@yahoo.es

Belgium

Earliest CTIS Part Ii Submission Date
14-02-2025
Latest Decision Or Authorization Date
13-04-2026
Processing Time Days
423
Number Of Sites
8
Number Of Participants
51

Sites

Site Name
UZ Leuven
Department Name
Pneumology
Contact Person Name
Wim Wuyts
Contact Person Email
wim.wuyts@uzleuven.be
Site Name
Hopital Erasme
Department Name
Pneumology
Contact Person Name
Benjamin Bondue
Contact Person Email
benjamin.bondue@hubruxelles.be
Site Name
Universitair Ziekenhuis Gent
Department Name
Pneumology
Contact Person Name
Geert Van Pottelberge
Contact Person Email
geert.vanpottelberge@uzgent.be
Site Name
Centre Hospitalier Universitaire De Liege
Department Name
Pneumology
Contact Person Name
Julien Guiot
Contact Person Email
j.guiot@chuliege.be
Site Name
Onze-Lieve-Vrouwziekenhuis
Department Name
Pneumology
Contact Person Name
Valerie Adam
Contact Person Email
valerie.adam@olvz-aalst.be
Site Name
Ziekenhuis Aan De Stroom
Department Name
Pneumology
Contact Person Name
Hans Slabbynck
Contact Person Email
hans.slabbynck@zna.be
Site Name
Cliniques Universitaires Saint-Luc
Department Name
Pneumology
Contact Person Name
Antoine Froidure
Site Name
Universitair Ziekenhuis Antwerpen
Department Name
Pneumology
Contact Person Name
Xavier Van Meerbeeck
Contact Person Email
xavier.vanmeerbeeck@uza.be

Sponsor

Primary sponsor

Full Name
United Therapeutics Corp.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Medpace Inc.
Responsibilities
Management of Clinical Event Adjudication
Name
Almac Clinical Services LLC
Responsibilities
Labelling/Distribution/QP Release/IoR, as required
Name
PPD Development LP
Responsibilities
Multiple sponsor duties (codes: 1,11,12,2,5) as listed in CTIS entry
Name
eResearchTechnology GmbH
Responsibilities
Surrogate endpoint test - Central Read of Spirometry and Training sites on 2019ATS guidelines
Name
Eresearchtechnology Inc.
Responsibilities
screening HRCT reviews

Third parties

  • {"country":"United States","full_name":"Medrio Inc.","duties_or_roles":"sponsorDuties code: 7","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"Management of Clinical Event Adjudication","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"Labelling/Distribution/QP Release/IoR, as required","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Elite Safety Sciences Inc.","duties_or_roles":"sponsorDuties code: 8","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"screening HRCT reviews","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"eResearchTechnology GmbH","duties_or_roles":"Surrogate endpoint test - Central Read of Spirometry and Training sites on 2019ATS guidelines","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties code: 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: 1, 11, 12, 2, 5","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Treprostinil
Active Substance
TREPROSTINIL
Modality
Small molecule
Routes Of Administration
Inhalation
Route
INHALATION USE
Maximum Dose
360 µg per day (maxDailyDoseAmount 360 µg)
Investigational Product Name
The Placebo Nebuliser Solution is a solution dosage form for nebulisation identical to Treprostinil Nebuliser Solution drug product except for the absence of the treprostinil drug substance.
Modality
Other

Related trials

Other published trials that may interest you.