Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis Clinical Trial

— TETON  

Official title:

A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04708782
• Other study ID #: RIN-PF-301
• Status: Recruiting
• Phase: Phase 3
• Start date: June 1, 2021
• Est. completion date: June 2025

Study information

• Verified date: June 2024
• Source: United Therapeutics
• Contact: United Therapeutics Global Medical Information
• Phone: 919-485-8350
• Email: clinicaltrials[@]unither.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 576
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Subject gives voluntary informed consent to participate in the study.

2. Subject is =40 years of age, inclusive, at the time of signing informed consent.

3. 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.

4. FVC =45% predicted at Screening.

5. 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.

6. 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.

7. 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.

8. 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: FEV1/FVC <0.70 at Screening.

3. 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.

4. 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.

5. 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.

6. The subject is receiving >10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.

7. 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.

8. Uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline.

9. 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.

10. 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.

11. Life expectancy <6 months due to IPF or a concomitant illness.

12. Acute pulmonary embolism within 90 days prior to Baseline.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Interstitial Lung Disease
• Lung Diseases
• Lung Diseases, Interstitial
• Pulmonary Fibrosis

Intervention

Drug:
• Placebo
Placebo administered QID
• Inhaled Treprostinil
Inhaled treprostinil (6 mcg/breath) administered QID

Device:
• Treprostinil Ultrasonic Nebulizer
Treprostinil ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.

Locations

Country	Name	City	State
Canada	Dynamic Drug Advancement Limited	Ajax	Ontario
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec-Universite	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Centre d'investigation Clinique Mauricie	Trois-Rivières	Quebec
Canada	St.Paul's Hospital	Vancouver	British Columbia
United States	University of New Mexico Health Sciences Center	Albuquerque	New Mexico
United States	University of Michigan Int Med Pulmonary and critical care	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	Piedmont Healthcare Atlanta	Atlanta	Georgia
United States	Johns Hopkins Asthma & Allergy Center	Baltimore	Maryland
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	The Lung Research Center	Chesterfield	Missouri
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	University of Cincinnati	Cincinnati	Ohio
United States	St. Francis Sleep Allergy & Lung Institute	Clearwater	Florida
United States	Cleveland Clinic	Cleveland	Ohio
United States	Prisma Health Midlands	Columbia	South Carolina
United States	The Ohio State University Wexner Medical Center - Martha Morehouse Medical Pavilion	Columbus	Ohio
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	National Jewish Health	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Clinical Trials Center of Middle Tennessee	Franklin	Tennessee
United States	University of Florida Health at Shands	Gainesville	Florida
United States	PulmonIx, LLC	Greensboro	North Carolina
United States	East Carolina University and Leo Jenkins Cancer Center	Greenville	North Carolina
United States	Penn State Milton S. Hershey Medical Center/Penn State College of Medicine	Hershey	Pennsylvania
United States	The Queen's Medical Center	Honolulu	Hawaii
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	Community Health Network	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Ascension St. Vincent's	Jacksonville	Florida
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	University of Florida	Jacksonville	Florida
United States	Jasper Summit Research, LLC	Jasper	Alabama
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	Pulmonary Disease Specialists, PA d/b/a PDS Research	Kissimmee	Florida
United States	Statecare Pulmonary Consultants	Knoxville	Tennessee
United States	UC San Diego Health	La Jolla	California
United States	St Joseph's Physician's Pulmonary Health	Liverpool	New York
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Louisville Pulmonary Care,PLLC	Louisville	Kentucky
United States	Norton Pulmonary Specialists	Louisville	Kentucky
United States	University of Louisville	Louisville	Kentucky
United States	University of Wisconsin School of Medicine and Public health	Madison	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	A & A Research Consultants, LLC	McAllen	Texas
United States	Metroplex Pulmonary and Sleep Center PA	McKinney	Texas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Intermountain Medical Center	Murray	Utah
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Northwell Health	New Hyde Park	New York
United States	LSU Health Sciences Center New Orleans	New Orleans	Louisiana
United States	Tulane University Medical Center	New Orleans	Louisiana
United States	NewportNativeMD, Inc	Newport Beach	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Creighton University Clinical Research Office	Omaha	Nebraska
United States	University of California, Irvine	Orange	California
United States	Central Florida Pulmonary Group, PA	Orlando	Florida
United States	Advanced Pulmonary Research Institute	Palm Beach	Florida
United States	Palmtree Clinical Research, Inc.	Palm Springs	California
United States	Temple Lung Center	Philadelphia	Pennsylvania
United States	Thoams Jefferson,Hospital University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists, Ltd.	Phoenix	Arizona
United States	Banner University Medical Center-Phoenix	Phoenix	Arizona
United States	St. Joseph's Hospital and Medical Center - Norton Thoracic Institute	Phoenix	Arizona
United States	Pinehurst Medical Clinic, Inc.	Pinehurst	North Carolina
United States	The Oregon Clinic, PC	Portland	Oregon
United States	Pulmonary Associates of Richmond, Inc.	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical center	Rochester	New York
United States	Clinical Research of Rock Hill	Rock Hill	South Carolina
United States	UC Davis Health Medical Center	Sacramento	California
United States	J&L Research, LLC	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Coastal Pulmonary & Critical Care PLC	Saint Petersburg	Florida
United States	University of Utah Health	Salt Lake City	Utah
United States	University of California - San Francisco	San Francisco	California
United States	LSU Health Science Center Shreveport	Shreveport	Louisiana
United States	Adventist Healthcare White Oak Medical CEnter	Silver Spring	Maryland
United States	Stanford University Medical Center	Stanford	California
United States	University of South Florida Health	Tampa	Florida
United States	Renovatio Clinical Consultants, LLC	The Woodlands	Texas
United States	University of Arizona	Tucson	Arizona
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Cleveland Clinic Florida	Weston	Florida
United States	Southeastern Research Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Absolute FVC from Baseline to Week 52	The FVC measurement indicates the amount of air a person can forcefully and quickly exhale after taking a deep breath.	Baseline to Week 52
Secondary	Time to Clinical Worsening	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.	Baseline to Week 52
Secondary	Time to First Acute Exacerbation of IPF	An exacerbation of IPF is defined as an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality.	Baseline to Week 52
Secondary	Overall Survival at Week 52	Vital status will be assessed for all subjects at Week 52, including those who discontinue the study prematurely or who withdraw consent.	Week 52
Secondary	Change in % Predicted FVC from 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.	Baseline to Week 52
Secondary	Change in K-BILD Questionnaire Score from 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).	Baseline to Week 52
Secondary	Change in DLCO from Baseline to Week 52	The DLCO measurement measures how well oxygen moves from the lungs to the blood.	Baseline to Week 52