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NCT05943535PHASE3Recruiting

Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)

United Therapeutics

Start Date

10/30/2023

Completion Date

11/1/2027

Summary

Study RIN-PF-305 is designed to evaluate the safety and efficacy of inhaled treprostinil in subjects with progressive pulmonary fibrosis (PPF) over a 52-week period.

Detailed Description

Study RIN-PF-305 is a Phase 3, multinational, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of inhaled treprostinil in subjects with PPF 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 (forced vital capacity \[FVC\]), time to clinical worsening, time to first acute exacerbation of interstitial lung disease (ILD), 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

Age Range: 18 years to No maximum

Inclusion Criteria: 1. Subject gives voluntary informed consent to participate in the study. 2. Subject is ≥18 years of age, inclusive, at the time of signing informed consent. 3. Subject has radiological evidence of pulmonary fibrosis of \>10% extent on an HRCT scan in the previous 12 months (confirmed by central review). 4. 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: 1. Clinically significant decline in % predicted FVC based on ≥10% relative decline 2. Marginal decline in % predicted FVC based on ≥5% to \<10% relative decline combined with worsening of respiratory symptoms 3. Marginal decline in % predicted FVC based on ≥5% to \<10% relative decline combined with increasing extent of fibrotic changes on chest imaging 4. Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging 5. FVC ≥45% predicted at Screening (confirmed by central review). 6. Subjects must be on 1 of the following: 1. On nintedanib or pirfenidone for ≥90 days prior to Baseline and in the Investigator's opinion, are planning to continue treatment through the study 2. 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. 7. 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. 8. Women of childbearing potential must be non-pregnant (as confirmed by a urine pregnancy test at Screening and Baseline) and non-lactating, and will agree to do 1 of the following: 1. Abstain from intercourse (when it is in line with their preferred and usual lifestyle) 2. Use 2 medically acceptable, highly effective forms of contraception for the duration of the study, and at least 30 days after discontinuing study drug. i. 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. 9. 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. 10. 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 (forced expiratory volume in 1 second/FVC \<0.70 at Screening) or greater extent of emphysema than fibrosis on HRCT (confirmed by central review). 3. Subject has a diagnosis of IPF. 4. 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. 5. 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), soluble guanylate cyclase stimulators, or activin signaling inhibitors (sotatercept) 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 prior to any study-related efficacy assessments. 6. Subject is receiving \>10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline. 7. 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. 8. Subject has uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline. 9. 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. 10. Acute pulmonary embolism within 90 days prior to Baseline. 11. 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. 12. In the opinion of the Investigator, life expectancy \<12 months due to ILD or a concomitant illness. 13. Subject has received nerandomilast within 60 days prior to Baseline.

Interventions

DRUG

Placebo

DRUG

Inhaled Treprostinil

DEVICE

Treprostinil Ultrasonic Nebulizer

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Conditions

Progressive Pulmonary FibrosisInterstitial Lung Disease

Locations

UAB Lung Health Center

Birmingham, Alabama 35233

United States

Banner University Medical Center Phoenix Lung Institute

Phoenix, Arizona 85006

United States

Norton Thoracic Institute

Phoenix, Arizona 85013

United States

Peter Morton Medical Building

Los Angeles, California 90095

United States

NewportNativeMD, Inc.

Newport Beach, California 92663

United States

University of California Irvine Medical Center

Orange, California 92868

United States

Paradigm Clinical Research

Redding, California 45227

United States

UC Davis Health Medical Center

Sacramento, California 95817

United States

Paradigm Clinical Research

San Diego, California 92108

United States

Stanford University Medical Center

Stanford, California 94305

United States

Georgetown University Hospital

Washington D.C., District of Columbia 20007

United States

Ascension Medical Group St. Vincent's Lung Institute

Jacksonville, Florida 32204

United States

Mayo Clinic

Jacksonville, Florida 32224

United States

TGH/USF Center for Advanced Lung Disease and Lung Transplant

Tampa, Florida 33606

United States

Cleveland Clinic Florida

Weston, Florida 33331

United States

The Emory Clinic

Atlanta, Georgia 45227

United States

Northwestern Memorial Hospital, Clinical Research Unit

Chicago, Illinois 60611

United States

Rush University Medical Center Outpatient Pulmonary Clinic

Chicago, Illinois 60612

United States

UI Health Hospital

Chicago, Illinois 60612

United States

Loyola University Medical Center

Maywood, Illinois 60153

United States

University of Kansas Medical Center

Kansas City, Kansas 66160

United States

University of Kentucky

Lexington, Kentucky 45227

United States

University of Louisville Healthcare Outpatient Research Clinic

Louisville, Kentucky 40202

United States

Tulane Medical Center

New Orleans, Louisiana 45227

United States

Johns Hopkins Asthma and Allergy Center

Baltimore, Maryland 21224

United States

University of Maryland Medical Center

Baltimore, Maryland 45227

United States

Adventist Healthcare White Oak Medical Center

Silver Spring, Maryland 20904

United States

Tufts Medical Center

Boston, Massachusetts 02111

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Infinity Medical Center

North Dartmouth, Massachusetts 02747

United States

Corewell Health Grand Rapids Hospitals - Butterworth

Grand Rapids, Michigan 49503

United States

Beaumont Hospital, Royal Oak

Royal Oak, Michigan 48073

United States

University of Minnesota Health Clinical Research Unit (CRU)

Minneapolis, Minnesota 55455

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Memorial Hospital at Gulfport

Gulfport, Mississippi 39501

United States

The Lung Research Center, LLC

Chesterfield, Missouri 63017

United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri 64111

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

University of New Mexico

Albuquerque, New Mexico 87131

United States

Northwell Health

New Hyde Park, New York 11042

United States

Weill Cornell Medicine, New York-Presbyterian Hospital

New York, New York 10065

United States

Stony Brook Advanced Specialty Care

Stony Brook, New York 11794-8172

United States

Montefiore Medical Center

The Bronx, New York 10467

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

PulmonIx LLC

Greensboro, North Carolina 27403

United States

East Carolina University

Greenville, North Carolina 27834

United States

Wake Forest Baptist Health

Winston-Salem, North Carolina 27104

United States

University of Cincinnati Medical Center

Cincinnati, Ohio 45219

United States

St. Luke's Univeristy Health Network-Pulmonary & Critical Care

Cincinnati, Ohio 45227

United States

The Ohio State University Wexner Medical CEnter

Columbus, Ohio 43201

United States

Mercy Health St.Vincent Medical Center LLC

Toledo, Ohio 43608

United States

Pennsylvania State Hershey Medical Center and College of Medicine

Hershey, Pennsylvania 17033

United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

Jefferson Honickman Center

Philadelphia, Pennsylvania 19107

United States

Temple University Hospital

Philadelphia, Pennsylvania 19140

United States

Medical University of South Carolina-Nexus

Charleston, South Carolina 29425

United States

Prisma Health Pulmonology-Richland

Columbia, South Carolina 29203

United States

Clinical Trials Center of Middle Tennessee, LLC

Franklin, Tennessee 37067

United States

StatCare Pulmonary Consultants, PLLC

Knoxville, Tennessee 37919

United States

The Vanderbilt Lung Institute

Nashville, Tennessee 37204

United States

Baylor University Medical Center

Dallas, Texas 75246

United States

UT Southwestern Medical Center-Advanced Lung Clinic

Dallas, Texas 75390

United States

Houston Methodist Outpatient Center

Houston, Texas 77030

United States

The University of Texas Health Science Center at Houston, McGovern Medical School

Houston, Texas 77030

United States

A & A Research Consultants, LLC

McAllen, Texas 78503

United States

Metroplex Pulmonary and Sleep Center

McKinney, Texas 75069

United States

Methodist Hospital

San Antonio, Texas 78229

United States

Intermountain Medical Center

Murray, Utah 84107

United States

University of Utah Health

Salt Lake City, Utah 84108

United States

University of Virginia Health System

Charlottesville, Virginia 22903

United States

Christopher King, MD

Falls Church, Virginia 22042

United States

Pulmonary Associates of Richmond, Inc.

Richmond, Virginia 23230

United States

University Hospital and UW Health Clinics

Madison, Wisconsin 53792

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53226-1222

United States

Instituto Ave Pulmo - Fundacion enfisema

Mar del Plata, Buenos Aires 7600

Argentina

Instituto Medico Rio Cuarto

Río Cuarto, Córdoba Province 5800

Argentina

Sanatorio Parque de Rosario - Consultorios Externos

Rosario, Santa Fe Province 2000

Argentina

Investigaciones en Patologias Respiratorias

San Miguel de Tucumán, Tucumán Province 4000

Argentina

CIMER-Centro Integral de Medicina Respiratoria

San Miguel de Tucumán, Tucumán Province

Argentina

CINME Centro de Investigaciones Metabolicas

Buenos Aires, C1056ABI

Argentina

Fundación Respirar

Buenos Aires, C1426ABP

Argentina

Instituto de Medicina Respiratoria

Córdoba, 5003

Argentina

Sanatorio Allende Cerro

Córdoba, 5021

Argentina

Royal Prince Alfred Hospital

Camperdown, New South Wales 2050

Australia

St George Hospital

Kogarah, New South Wales 2217

Australia

The Prince Charles Hospital

Brisbane, Queensland Australia

Australia

Lung Research QLD

Chermside, Queensland 4032

Australia

Eastern Health Box Hill Hospital

Box Hill, Victoria 3128

Australia

Monash Health-Monash Medical Centre

Clayton, Victoria 3168

Australia

Austin Health

Heidelberg, Victoria 3084

Australia

Institute for Respiratory Health - Midland

Midland, Western Australia 6056

Australia

Institute for Respiratory Health

Nedlands, Western Australia 6009

Australia

AZORG

Aalst, 9300

Belgium

ZAS Middelheim

Antwerp, 2020

Belgium

CUB Hopital Erasmde

Brussels, 1070

Belgium

Cliniques Universitaires St.-Luc

Brussels, 1200

Belgium

Universitair Ziekenhuis Gent

Ghent, 9000

Belgium

UZ Leuven

Leuven, 3000

Belgium

CHU de Liège

Liège, 4000

Belgium

St.Paul's Hospital

Vancouver, British Columbia V6Z 176

Canada

Dynamic Drug Advancement Limited

Ajax, Ontario L1S 2J5

Canada

St.Joseph's Healthcare Hamilton

Hamilton, Ontario L8N 4A6

Canada

Hôpital Maisonneuve-Rosemont

Montreal, Quebec H1T 2M4

Canada

CIC Mauricie inc.

Québec, Quebec G8T 7A1

Canada

Diex Recherche Inc. - Division Sherbrooke Est

Sherbrooke, Quebec J1E 0N8

Canada

Royal University Hospital

Saskatoon, Saskatchewan S7N 0W8

Canada

Centro de Investigacion Curico

Curicó, Maule Region 3341643

Chile

CEC Centro Estudios Clinicos

Santiago, Santiago Metropolitan 7550495

Chile

Fundacion Medica San Cristobal

Santiago, Santiago Metropolitan 7630226

Chile

Biocinetic Ltda.

Santiago, Santiago Metropolitan 8320000

Chile

Centro Respiratorio Integral LTDA. (CENRESIN)

Quillota, Valparaiso 2260000

Chile

Centro de Investigación de Enfermedades Respiratorias e Inmunológicas (CIERI)

Viña del Mar, Valparaiso 2520000

Chile

Hôpital Avicennes

Bobigny, 93000

France

Hospices civils de Lyon - Hôpital Louis Pradel

Bron, 69500

France

CHU Caen Normandie

Caen, 14000

France

Assistance Publique Hôpitaux de Marseille - centre Hospitalier Régional de Marseille

Marseille,

France

Rouen University Hospital

Rouen, 7600

France

Centre Hospitalier Régional Universitaire de Tours

Tours, Tours Cedex 9

France

RoMed Klinikum Rosenheim-Ellmaierstr. 23

Rosenheim, Bavaria 83022

Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony 30625

Germany

Zentralklinik Bad Berka GmbH Klinik für Pneumologie, Zentrum für Schlaf-und Beatmungsmedizin

Bad Berka, 99437

Germany

Prufstelle der GWT am Fachkrankenhaus Coswig

Coswig, 01640

Germany

uhrlandklinik Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

Essen, 45239

Germany

Lungenfachklinik Immenhausen

Immenhausen, 34376

Germany

SLK Kliniken Heilbronn GmbH

Löwenstein, 74245

Germany

LMU Klinikum Medizinische Klinik und Poliklinik V

München, 81377

Germany

Barzilai Medical Center

Ashkelon, 7830604

Israel

Hillel Yaffe Medical Center

Hadera, 3846201

Israel

Rabin Medical Center

Haifa, 3436212

Israel

Shaare Zedek Medical Center

Jerusalem, 9103102

Israel

The Hadassah University Medical Center Ein Kerem Hospital

Jerusalem, 9112001

Israel

Meir Medical Center

Kfar Saba, 4428164

Israel

Rabin Medical Center

Petah Tikva, 4941492

Israel

Kaplan Medical Center

Rehovot, 7551041

Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906

Israel

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

Catania, 95123

Italy

Azienda Unita Sanitaria Locale Della Romagna Ospedale "Gian Battista Morgagni - Luigi Pierantoni" di Forlì

Forlì, 47121

Italy

Azienda Ospedaliero-Universitaria di Modena Policlinico di Modena

Modena, 41124

Italy

Fondazione IRCCS San Gerardo dei Tintori

Monza,

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 168

Italy

Azienda Ospedaliero-Universitaria Senese

Siena, 53100

Italy

Centro Ricerche Cliniche di Verona SrL Pneumology Unit

Verona, 37134

Italy

Canterbury Respiratory Research Group

Christchurch, Canterbury 8011

New Zealand

Aotearoa Clinical Trials Trust- Middlemore Hospital

Auckland,

New Zealand

Waikato Hospital

Hamilton, 3204

New Zealand

Hospital Nacional Adolfo Guevara Velasco

Cusco, 08002

Peru

Clinica Internacional - Sede Lima

Lima, 15001

Peru

Unidad de Investigacion de Enfermedades Respiratorias- Clinica San Pablo -Surco

Lima, 15023

Peru

Clinica Ricardo Palma

Lima, 15036

Peru

Hospital Central de la Fuerza Aerea del Peru

Lima, 15046

Peru

Centro de Investigacion de Enfermedades Respiratorias - Clinica Providencia

Lima, 15088

Peru

Gachon University Gil Medical Center

Incheon, 21565

South Korea

Seoul National University Bundang Hospital

Seongnam-si, 13620

South Korea

Korea University Anam Hospital

Seoul, 02841

South Korea

Asan Medical Center

Seoul, 05505

South Korea

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

Seoul, 3312

South Korea

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807

Taiwan

Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301

Taiwan

Taichung Veterans General Hospital

Taichung, 40705

Taiwan

Birmingham Heartlands Hospital

Birmingham,

United Kingdom

Royal Papworth Hospital

Cambridge, CB2 0AY

United Kingdom

NHS Lothian, Royal INfirmary of Edingburgh

Edinburgh, EH16 4SA

United Kingdom

Guy's Hospital

London, SE1 9RT

United Kingdom

Manchester University NHS Foundation Trust, North Manchester General Hospital

Manchester, M8 5RB

United Kingdom

NHS Tayside, Perth Royal Infirmary

Perth, PH1 1NX

United Kingdom