Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
Purpose
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.
Conditions
- Progressive Pulmonary Fibrosis
- Interstitial Lung Disease
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Placebo Comparator Placebo |
Matching placebo inhaled using an ultrasonic nebulizer QID |
|
|
Experimental 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. |
|
Recruiting Locations
UAB Lung Health Center
Birmingham 4049979, Alabama 4829764 35233
Birmingham 4049979, Alabama 4829764 35233
Norton Thoracic Institute
Phoenix 5308655, Arizona 5551752 85013
Phoenix 5308655, Arizona 5551752 85013
Peter Morton Medical Building
Los Angeles 5368361, California 5332921 90095
Los Angeles 5368361, California 5332921 90095
NewportNativeMD, Inc.
Newport Beach 5376890, California 5332921 92663
Newport Beach 5376890, California 5332921 92663
University of California Irvine Medical Center
Orange 5379513, California 5332921 92868
Orange 5379513, California 5332921 92868
Paradigm Clinical Research
Redding 5570160, California 5332921 45227
Redding 5570160, California 5332921 45227
UC Davis Health Medical Center
Sacramento 5389489, California 5332921 95817
Sacramento 5389489, California 5332921 95817
Paradigm Clinical Research
San Diego 5391811, California 5332921 92108
San Diego 5391811, California 5332921 92108
Stanford University Medical Center
Stanford 5398563, California 5332921 94305
Stanford 5398563, California 5332921 94305
Georgetown University Hospital
Washington D.C. 4140963, District of Columbia 4138106 20007
Washington D.C. 4140963, District of Columbia 4138106 20007
Ascension Medical Group St. Vincent's Lung Institute
Jacksonville 4160021, Florida 4155751 32204
Jacksonville 4160021, Florida 4155751 32204
Mayo Clinic
Jacksonville 4160021, Florida 4155751 32224
Jacksonville 4160021, Florida 4155751 32224
TGH/USF Center for Advanced Lung Disease and Lung Transplant
Tampa 4174757, Florida 4155751 33606
Tampa 4174757, Florida 4155751 33606
The Emory Clinic
Atlanta 4180439, Georgia 4197000 45227
Atlanta 4180439, Georgia 4197000 45227
Northwestern Memorial Hospital, Clinical Research Unit
Chicago 4887398, Illinois 4896861 60611
Chicago 4887398, Illinois 4896861 60611
Rush University Medical Center Outpatient Pulmonary Clinic
Chicago 4887398, Illinois 4896861 60612
Chicago 4887398, Illinois 4896861 60612
Loyola University Medical Center
Maywood 4901514, Illinois 4896861 60153
Maywood 4901514, Illinois 4896861 60153
University of Kansas Medical Center
Kansas City 4273837, Kansas 4273857 66160
Kansas City 4273837, Kansas 4273857 66160
University of Kentucky
Lexington 4297983, Kentucky 6254925 45227
Lexington 4297983, Kentucky 6254925 45227
University of Louisville Healthcare Outpatient Research Clinic
Louisville 4299276, Kentucky 6254925 40202
Louisville 4299276, Kentucky 6254925 40202
Tulane Medical Center
New Orleans 4335045, Louisiana 4331987 45227
New Orleans 4335045, Louisiana 4331987 45227
Johns Hopkins Asthma and Allergy Center
Baltimore 4347778, Maryland 4361885 21224
Baltimore 4347778, Maryland 4361885 21224
Adventist Healthcare White Oak Medical Center
Silver Spring 4369596, Maryland 4361885 20904
Silver Spring 4369596, Maryland 4361885 20904
Tufts Medical Center
Boston 4930956, Massachusetts 6254926 02111
Boston 4930956, Massachusetts 6254926 02111
Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114
Boston 4930956, Massachusetts 6254926 02114
Infinity Medical Center
North Dartmouth 4945601, Massachusetts 6254926 02747
North Dartmouth 4945601, Massachusetts 6254926 02747
Beaumont Hospital, Royal Oak
Royal Oak 5007804, Michigan 5001836 48073
Royal Oak 5007804, Michigan 5001836 48073
University of Minnesota Health Clinical Research Unit (CRU)
Minneapolis 5037649, Minnesota 5037779 55455
Minneapolis 5037649, Minnesota 5037779 55455
Mayo Clinic
Rochester 5043473, Minnesota 5037779 55905
Rochester 5043473, Minnesota 5037779 55905
The Lung Research Center, LLC
Chesterfield 4381072, Missouri 4398678 63017
Chesterfield 4381072, Missouri 4398678 63017
Saint Luke's Hospital of Kansas City
Kansas City 4393217, Missouri 4398678 64111
Kansas City 4393217, Missouri 4398678 64111
Washington University School of Medicine
St Louis 4407066, Missouri 4398678 63110
St Louis 4407066, Missouri 4398678 63110
University of New Mexico
Albuquerque 5454711, New Mexico 5481136 87131
Albuquerque 5454711, New Mexico 5481136 87131
Northwell Health
New Hyde Park 5128514, New York 5128638 11042
New Hyde Park 5128514, New York 5128638 11042
Weill Cornell Medicine, New York-Presbyterian Hospital
New York 5128581, New York 5128638 10065
New York 5128581, New York 5128638 10065
Stony Brook Advanced Specialty Care
Stony Brook 5139865, New York 5128638 11794-8172
Stony Brook 5139865, New York 5128638 11794-8172
Montefiore Medical Center
The Bronx 5110266, New York 5128638 10467
The Bronx 5110266, New York 5128638 10467
Duke University Medical Center
Durham 4464368, North Carolina 4482348 27710
Durham 4464368, North Carolina 4482348 27710
PulmonIx LLC
Greensboro 4469146, North Carolina 4482348 27403
Greensboro 4469146, North Carolina 4482348 27403
East Carolina University
Greenville 4469160, North Carolina 4482348 27834
Greenville 4469160, North Carolina 4482348 27834
University of Cincinnati Medical Center
Cincinnati 4508722, Ohio 5165418 45219
Cincinnati 4508722, Ohio 5165418 45219
The Ohio State University Wexner Medical CEnter
Columbus 4509177, Ohio 5165418 43201
Columbus 4509177, Ohio 5165418 43201
Mercy Health St.Vincent Medical Center LLC
Toledo 5174035, Ohio 5165418 43608
Toledo 5174035, Ohio 5165418 43608
Pennsylvania State Hershey Medical Center and College of Medicine
Hershey 5193342, Pennsylvania 6254927 17033
Hershey 5193342, Pennsylvania 6254927 17033
Hospital of the University of Pennsylvania
Philadelphia 4560349, Pennsylvania 6254927 19104
Philadelphia 4560349, Pennsylvania 6254927 19104
Temple University Hospital
Philadelphia 4560349, Pennsylvania 6254927 19140
Philadelphia 4560349, Pennsylvania 6254927 19140
Medical University of South Carolina-Nexus
Charleston 4574324, South Carolina 4597040 29425
Charleston 4574324, South Carolina 4597040 29425
Prisma Health Pulmonology-Richland
Columbia 4575352, South Carolina 4597040 29203
Columbia 4575352, South Carolina 4597040 29203
Clinical Trials Center of Middle Tennessee, LLC
Franklin 4623560, Tennessee 4662168 37067
Franklin 4623560, Tennessee 4662168 37067
StatCare Pulmonary Consultants, PLLC
Knoxville 4634946, Tennessee 4662168 37919
Knoxville 4634946, Tennessee 4662168 37919
The Vanderbilt Lung Institute
Nashville 4644585, Tennessee 4662168 37204
Nashville 4644585, Tennessee 4662168 37204
Baylor University Medical Center
Dallas 4684888, Texas 4736286 75246
Dallas 4684888, Texas 4736286 75246
UT Southwestern Medical Center-Advanced Lung Clinic
Dallas 4684888, Texas 4736286 75390
Dallas 4684888, Texas 4736286 75390
Houston Methodist Outpatient Center
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
The University of Texas Health Science Center at Houston, McGovern Medical School
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
A & A Research Consultants, LLC
McAllen 4709796, Texas 4736286 78503
McAllen 4709796, Texas 4736286 78503
Metroplex Pulmonary and Sleep Center
McKinney 4710178, Texas 4736286 75069
McKinney 4710178, Texas 4736286 75069
Intermountain Medical Center
Murray 5778755, Utah 5549030 84107
Murray 5778755, Utah 5549030 84107
University of Utah Health
Salt Lake City 5780993, Utah 5549030 84108
Salt Lake City 5780993, Utah 5549030 84108
University of Virginia Health System
Charlottesville 4752031, Virginia 6254928 22903
Charlottesville 4752031, Virginia 6254928 22903
Christopher King, MD
Falls Church 4758390, Virginia 6254928 22042
Falls Church 4758390, Virginia 6254928 22042
Pulmonary Associates of Richmond, Inc.
Richmond 4781708, Virginia 6254928 23230
Richmond 4781708, Virginia 6254928 23230
University Hospital and UW Health Clinics
Madison 5261457, Wisconsin 5279468 53792
Madison 5261457, Wisconsin 5279468 53792
Medical College of Wisconsin
Milwaukee 5263045, Wisconsin 5279468 53226-1222
Milwaukee 5263045, Wisconsin 5279468 53226-1222
More Details
- Status
- Recruiting
- Sponsor
- United Therapeutics
Study Contact
United Therapeutics Global Medical Information919-485-8350
clinicaltrials@unither.com
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.