Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
- Conditions
- Idiopathic Pulmonary FibrosisInterstitial Lung Disease
- Interventions
- Registration Number
- NCT04708782
- Lead Sponsor
- United Therapeutics
- Brief Summary
Study RIN-PF-301 is 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-301 is a multicenter, 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 & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 576
- Subject gives voluntary informed consent to participate in the study.
- Subject is ≥40 years of age, inclusive, at the time of signing informed consent.
- 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.
- FVC ≥45% predicted at Screening.
- 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.
- 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.
- 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.
- 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: FEV1/FVC <0.70 at Screening.
- 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.
- 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.
- 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.
- The subject is receiving >10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
- 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.
- Uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 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.
- 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.
- Life expectancy <6 months due to IPF or a concomitant illness.
- Acute pulmonary embolism within 90 days prior to Baseline.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 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. 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.
- 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 Clinical Worsening Baseline to Week 52 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.
Time to First Acute Exacerbation of IPF Baseline to Week 52 An exacerbation of IPF 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 ethnicity, sex, age, height, and weight.
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 interstitial lung disease (ILD) consisting of 3 domains (breathlessness and activities, psychological, and chest symptoms).
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 (101)
The University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Banner University Medical Center-Phoenix
🇺🇸Phoenix, Arizona, United States
Arizona Pulmonary Specialists, Ltd.
🇺🇸Phoenix, Arizona, United States
St. Joseph's Hospital and Medical Center - Norton Thoracic Institute
🇺🇸Phoenix, Arizona, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
UC San Diego Health
🇺🇸La Jolla, California, United States
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
NewportNativeMD, Inc
🇺🇸Newport Beach, California, United States
University of California, Irvine
🇺🇸Orange, California, United States
Palmtree Clinical Research, Inc.
🇺🇸Palm Springs, California, United States
UC Davis Health Medical Center
🇺🇸Sacramento, California, United States
University of California - San Francisco
🇺🇸San Francisco, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
St. Francis Sleep Allergy & Lung Institute
🇺🇸Clearwater, Florida, United States
University of Florida Health at Shands
🇺🇸Gainesville, Florida, United States
Ascension St. Vincent's
🇺🇸Jacksonville, Florida, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
University of Florida
🇺🇸Jacksonville, Florida, United States
Pulmonary Disease Specialists, PA d/b/a PDS Research
🇺🇸Kissimmee, Florida, United States
Lakeland Regional Health
🇺🇸Lakeland, Florida, United States
Central Florida Pulmonary Group, PA
🇺🇸Orlando, Florida, United States
Coastal Pulmonary & Critical Care PLC
🇺🇸Saint Petersburg, Florida, United States
University of South Florida Health
🇺🇸Tampa, Florida, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Piedmont Healthcare Atlanta
🇺🇸Atlanta, Georgia, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
The Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Rush University Medical Center Outpatient Pulmonary Clinic
🇺🇸Chicago, Illinois, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Community Health Network
🇺🇸Indianapolis, Indiana, United States
The University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Norton Pulmonary Specialists
🇺🇸Louisville, Kentucky, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
LSU Health Sciences Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Tulane University Medical Center
🇺🇸New Orleans, Louisiana, United States
LSU Health Science Center Shreveport
🇺🇸Shreveport, Louisiana, United States
Johns Hopkins Asthma & 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
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan Int Med Pulmonary and critical care
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Corewell Health William Beaumont Hospital
🇺🇸Royal Oak, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
The Lung Research Center
🇺🇸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
Creighton University Clinical Research Office
🇺🇸Omaha, Nebraska, United States
University of New Mexico Health Sciences Center
🇺🇸Albuquerque, New Mexico, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
St Joseph's Physician's Pulmonary Health
🇺🇸Liverpool, New York, United States
Northwell Health
🇺🇸New Hyde Park, New York, United States
University of Rochester Medical center
🇺🇸Rochester, New York, United States
Stony Brook Advanced Specialty Care
🇺🇸Stony Brook, New York, United States
PulmonIx, LLC
🇺🇸Greensboro, North Carolina, United States
East Carolina University and Leo Jenkins Cancer Center
🇺🇸Greenville, North Carolina, United States
Southeastern Research Center
🇺🇸Winston-Salem, North Carolina, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
The Ohio State University Wexner Medical Center - Martha Morehouse Medical Pavilion
🇺🇸Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
The Oregon Clinic, PC
🇺🇸Portland, Oregon, United States
Penn State Milton S. Hershey Medical Center/Penn State College of Medicine
🇺🇸Hershey, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Thoams Jefferson,Hospital University
🇺🇸Philadelphia, Pennsylvania, United States
Temple Lung Center
🇺🇸Philadelphia, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Prisma Health Midlands
🇺🇸Columbia, South Carolina, United States
Clinical Research of Rock Hill
🇺🇸Rock Hill, South Carolina, United States
Clinical Trials Center of Middle Tennessee
🇺🇸Franklin, Tennessee, United States
Statecare Pulmonary Consultants
🇺🇸Knoxville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Univrsity of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Premier Pulmonary Critical Care and Sleep Medicine
🇺🇸Denison, Texas, United States
Baylor Clinic-Baylor College of Medicine
🇺🇸Houston, Texas, United States
The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
A & A Research Consultants, LLC
🇺🇸McAllen, Texas, United States
Metroplex Pulmonary and Sleep Center PA
🇺🇸McKinney, Texas, United States
Renovatio Clinical Consultants, LLC
🇺🇸The Woodlands, 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
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Pulmonary Associates of Richmond, Inc.
🇺🇸Richmond, Virginia, United States
University of Wisconsin School of Medicine and Public health
🇺🇸Madison, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
St.Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Dynamic Drug Advancement Limited
🇨🇦Ajax, Ontario, Canada
St. Joseph's Healthcare Hamilton
🇨🇦Hamilton, Ontario, Canada
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Centre d'investigation Clinique Mauricie
🇨🇦Trois-Rivières, Quebec, Canada
Institut Universitaire de Cardiologie et de Pneumologie de Quebec-Universite
🇨🇦Quebec, Canada
Fundacion Medica San Cristobal
🇨🇱Santiago, Region Metropolitana, Chile
Centro Respiratorio Integral LTDA. (CENRESIN)
🇨🇱Quillota, Valparaiso, Chile