Clinical trial NCT04708782: Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Interstitial Lung Disease
Keywords: Treprostinil
IPF
ILD
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-01-14
Enrollment: 576
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Absolute FVC from Baseline to Week 52
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: Time to Clinical Worsening
timeFrame: Baseline to Week 52
measure: Time to First Acute Exacerbation of IPF
timeFrame: Baseline to Week 52
measure: Overall Survival at Week 52
timeFrame: Week 52
measure: Change in % Predicted FVC from Baseline to Week 52
timeFrame: Baseline to Week 52
measure: Change in K-BILD Questionnaire Score from Baseline to Week 52
timeFrame: Baseline to Week 52
measure: Change in DLCO from Baseline to Week 52
timeFrame: Baseline to Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Banner University Medical Center-Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists, Ltd.
state: Arizona
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center - Norton Thoracic Institute
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Health
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Newport Beach
country: United States
facility: NewportNativeMD, Inc
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Palm Springs
country: United States
facility: Palmtree Clinical Research, Inc.
state: California
city: Sacramento
country: United States
facility: UC Davis Health Medical Center
state: California
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Clearwater
country: United States
facility: St. Francis Sleep Allergy & Lung Institute
state: Florida
city: Gainesville
country: United States
facility: University of Florida Health at Shands
state: Florida
city: Jacksonville
country: United States
facility: Ascension St. Vincent's
state: Florida
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Kissimmee
country: United States
facility: Pulmonary Disease Specialists, PA d/b/a PDS Research
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Health
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group, PA
state: Florida
city: Saint Petersburg
country: United States
facility: Coastal Pulmonary & Critical Care PLC
state: Florida
city: Tampa
country: United States
facility: University of South Florida Health
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Piedmont Healthcare Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Honolulu
country: United States
facility: The Queen's Medical Center
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center Outpatient Pulmonary Clinic
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Norton Pulmonary Specialists
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: LSU Health Sciences Center New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Shreveport
country: United States
facility: LSU Health Science Center Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Asthma & Allergy Center
state: Maryland
city: Silver Spring
country: United States
facility: Adventist Healthcare White Oak Medical CEnter
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Int Med Pulmonary and critical care
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Royal Oak
country: United States
facility: Corewell Health William Beaumont Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Chesterfield
country: United States
facility: The Lung Research Center
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Creighton University Clinical Research Office
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Liverpool
country: United States
facility: St Joseph's Physician's Pulmonary Health
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Advanced Specialty Care
state: New York
city: Greensboro
country: United States
facility: PulmonIx, LLC
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University and Leo Jenkins Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Southeastern Research Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center - Martha Morehouse Medical Pavilion
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: The Oregon Clinic, PC
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center/Penn State College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thoams Jefferson,Hospital University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple Lung Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Prisma Health Midlands
state: South Carolina
city: Rock Hill
country: United States
facility: Clinical Research of Rock Hill
state: South Carolina
city: Franklin
country: United States
facility: Clinical Trials Center of Middle Tennessee
state: Tennessee
city: Knoxville
country: United States
facility: Statecare Pulmonary Consultants
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: Univrsity of Texas Southwestern Medical Center
state: Texas
city: Denison
country: United States
facility: Premier Pulmonary Critical Care and Sleep Medicine
state: Texas
city: Houston
country: United States
facility: Baylor Clinic-Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: McAllen
country: United States
facility: A & A Research Consultants, LLC
state: Texas
city: McKinney
country: United States
facility: Metroplex Pulmonary and Sleep Center PA
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical Consultants, LLC
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond, Inc.
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin School of Medicine and Public health
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: St.Paul's Hospital
state: British Columbia
city: Ajax
country: Canada
facility: Dynamic Drug Advancement Limited
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Trois-Rivières
country: Canada
facility: Centre d'investigation Clinique Mauricie
state: Quebec
city: Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Quebec-Universite
city: Santiago
country: Chile
facility: Fundacion Medica San Cristobal
state: Region Metropolitana
city: Quillota
country: Chile
facility: Centro Respiratorio Integral LTDA. (CENRESIN)
state: Valparaiso
Study officials:
References: