Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
- Conditions
- Progressive Pulmonary FibrosisInterstitial Lung Disease
- Interventions
- Registration Number
- NCT05943535
- Lead Sponsor
- United Therapeutics
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 698
-
Subject gives voluntary informed consent to participate in the study.
-
Subject is ≥18 years of age, inclusive, at the time of signing informed consent.
-
Subject has radiological evidence of pulmonary fibrosis of >10% extent on an HRCT scan in the previous 12 months (confirmed by central review).
-
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:
- Clinically significant decline in % predicted FVC based on ≥10% relative decline
- Marginal decline in % predicted FVC based on ≥5% to <10% relative decline combined with worsening of respiratory symptoms
- Marginal decline in % predicted FVC based on ≥5% to <10% relative decline combined with increasing extent of fibrotic changes on chest imaging
- Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging
-
FVC ≥45% predicted at Screening (confirmed by central review).
-
Subjects must be on 1 of the following:
- On nintedanib or pirfenidone for ≥90 days prior to Baseline and in the Investigator's opinion, are planning to continue treatment through the study
- 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.
-
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.
-
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:
- Abstain from intercourse (when it is in line with their preferred and usual lifestyle)
- 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.
-
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.
-
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 (forced expiratory volume in 1 second/FVC <0.70 at Screening) or greater extent of emphysema than fibrosis on HRCT (confirmed by central review).
- Subject has a diagnosis of IPF.
- 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.
- 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 prior to any study-related efficacy assessments.
- Subject is receiving >10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
- 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.
- Subject has uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline.
- 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.
- Acute pulmonary embolism within 90 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.
- In the opinion of the Investigator, life expectancy <12 months due to ILD or a concomitant illness.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 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. 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.
- 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 Clinical Worsening Baseline to Week 52 Clinical worsening is monitored from randomization until 1 of the following criteria are 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 ILD consisting of 3 domains (breathlessness and activities, psychological, and chest symptoms).
Time to First Acute Exacerbation of ILD Baseline to Week 52 An exacerbation of ILD is defined as an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality.
Overall Survival at Week 52 Week 52 Vital status will be assessed for all subjects at Week 52, including those who discontinue the study prematurely or who withdraw consent.
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 race, sex, age, height, and weight.
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 (115)
UAB Lung Health Center
🇺🇸Birmingham, Alabama, United States
Norton Thoracic Institute
🇺🇸Phoenix, Arizona, United States
Peter Morton Medical Building
🇺🇸Los Angeles, California, United States
NewportNativeMD, Inc.
🇺🇸Newport Beach, California, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
UC Davis Health Medical Center
🇺🇸Sacramento, California, United States
Paradigm Clinical Research
🇺🇸San Diego, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Ascension Medical Group St. Vincent's Lung Institute
🇺🇸Jacksonville, Florida, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
TGH/USF Center for Advanced Lung Disease and Lung Transplant
🇺🇸Tampa, Florida, United States
The Emory Clinic
🇺🇸Atlanta, Georgia, United States
Northwestern Memorial Hospital, Clinical Research Unit
🇺🇸Chicago, Illinois, United States
Rush University Medical Center Outpatient Pulmonary Clinic
🇺🇸Chicago, Illinois, United States
UI Health Hospital
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
University of Louisville Healthcare Outpatient Research Clinic
🇺🇸Louisville, Kentucky, United States
Tulane Medical Center
🇺🇸New Orleans, Louisiana, United States
Johns Hopkins Asthma and Allergy Center
🇺🇸Baltimore, Maryland, United States
Adventist Healthcare White Oak Medical Center
🇺🇸Silver Spring, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Infinity Medical Center
🇺🇸North Dartmouth, Massachusetts, United States
Beaumont Hospital, Royal Oak
🇺🇸Royal Oak, Michigan, United States
University of Minnesota Health Clinical Research Unit (CRU)
🇺🇸Minneapolis, Minnesota, United States
The Lung Research Center, LLC
🇺🇸Chesterfield, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Northwell Health
🇺🇸New Hyde Park, New York, United States
Weill Cornell Medicine, New York-Presbyterian Hospital
🇺🇸New York, New York, United States
Stony Brook Advanced Specialty Care
🇺🇸Stony Brook, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
PulmonIx LLC
🇺🇸Greensboro, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
The Ohio State University Wexner Medical CEnter
🇺🇸Columbus, Ohio, United States
Mercy Health St.Vincent Medical Center LLC
🇺🇸Toledo, Ohio, United States
Pennsylvania State Hershey Medical Center and College of Medicine
🇺🇸Hershey, Pennsylvania, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Medical University of South Carolina-Nexus
🇺🇸Charleston, South Carolina, United States
Prisma Health Pulmonology-Richland
🇺🇸Columbia, South Carolina, United States
Clinical Trials Center of Middle Tennessee, LLC
🇺🇸Franklin, Tennessee, United States
StatCare Pulmonary Consultants, PLLC
🇺🇸Knoxville, Tennessee, United States
The Vanderbilt Lung Institute
🇺🇸Nashville, Tennessee, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center-Advanced Lung Clinic
🇺🇸Dallas, Texas, United States
Houston Methodist Outpatient Center
🇺🇸Houston, Texas, United States
The University of Texas Health Science Center at Houston, McGovern Medical School
🇺🇸Houston, Texas, United States
A & A Research Consultants, LLC
🇺🇸McAllen, Texas, United States
Metroplex Pulmonary and Sleep Center
🇺🇸McKinney, Texas, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
University of Utah Health
🇺🇸Salt Lake City, Utah, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Christopher King, MD
🇺🇸Falls Church, Virginia, United States
Pulmonary Associates of Richmond, Inc.
🇺🇸Richmond, Virginia, United States
University Hospital and UW Health Clinics
🇺🇸Madison, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Instituto Ave Pulmo - Fundacion enfisema
🇦🇷Mar Del Plata, Buenos Aires, Argentina
Instituto Medico Rio Cuarto
🇦🇷Río Cuarto, Cordoba, Argentina
Sanatorio Parque de Rosario - Consultorios Externos
🇦🇷Rosario, Santa Fe, Argentina
Investigaciones en Patologias Respiratorias
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
CIMER-Centro Integral de Medicina Respiratoria
🇦🇷San Miguel De Tucumán, Tucumán, Argentina
CINME Centro de Investigaciones Metabolicas
🇦🇷Ciudad Autonoma de Buenos aires, Argentina
Fundación Respirar
🇦🇷Ciudad Autónoma de Buenos Aires, Argentina
Instituto de Medicina Respiratoria
🇦🇷Cordoba, Argentina
Sanatorio Allende Cerro
🇦🇷Córdoba, Argentina
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
The Prince Charles Hospital
🇦🇺Brisbane, Queensland, Australia
Eastern Health Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Monash Health-Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Institute for Respiratory Health - Midland
🇦🇺Midland, West Australia, Australia
Institute for Respiratory Health
🇦🇺Nedlands, Western Australia, Australia
AZORG
🇧🇪Aalst, Belgium
CUB Hopital Erasmde
🇧🇪Brussels, Belgium
Cliniques Universitaires St.-Luc
🇧🇪Brussels, Belgium
CHU de Liège
🇧🇪Liège, Belgium
St.Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Dynamic Drug Advancement Limited
🇨🇦Ajax, Ontario, Canada
St.Joseph's Healthcare Hamilton
🇨🇦Hamilton, Ontario, Canada
Hôpital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
CIC Mauricie inc.
🇨🇦Québec, Quebec, Canada
Centro de Investigacion Curico
🇨🇱Curicó, Maule, Chile
CEC Centro Estudios Clinicos
🇨🇱Santiago, Region Metropolitana, Chile
Fundacion Medica San Cristobal
🇨🇱Santiago, Region Metropolitana, Chile
Biocinetic Ltda.
🇨🇱Santiago, Region Metropolitana, Chile
Centro Respiratorio Integral LTDA. (CENRESIN)
🇨🇱Quillota, Valparaiso, Chile
Centro de Investigación de Enfermedades Respiratorias e Inmunológicas (CIERI)
🇨🇱Viña Del Mar, Valparaíso, Chile
Hôpital Avicennes
🇫🇷Bobigny, France
Hospices civils de Lyon - Hôpital Louis Pradel
🇫🇷Bron, France
CHU Caen Normandie
🇫🇷Caen, France
Assistance Publique Hôpitaux de Marseille - centre Hospitalier Régional de Marseille
🇫🇷Marseille, France
Centre Hospitalier Régional Universitaire de Tours
🇫🇷Tours Cedex 9, France
Hillel Yaffe Medical Center
🇮🇱Hadera, Israel
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Meir Medical Center
🇮🇱Kfar Saba, Israel
Kaplan Medical Center
🇮🇱Reẖovot, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Eunpyeong St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Canterbury Respiratory Research Group
🇳🇿Christchurch, Canterbury, New Zealand
Aotearoa Clinical Trials Trust- Middlemore Hospital
🇳🇿Auckland, New Zealand
Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan