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

Sponsor

United Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04708782

Collaborator

(none)

396

Enrollment

Locations

Arms

Anticipated Duration (Months)

7.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study RIN-PF-301 is designed to evaluate the safety and efficacy of inhaled treprostinil in subjects with idiopathic pulmonary fibrosis (IPF) over a 52-week period.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis Interstitial Lung Disease	Drug: Placebo Drug: Inhaled Treprostinil Device: Treprostinil Ultrasonic Nebulizer	Phase 3

Detailed Description

Study RIN-PF-301 is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of inhaled treprostinil 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 (forced vital capacity [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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

396 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 1, 2021

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Matching placebo inhaled using an ultrasonic nebulizer QID	Drug: Placebo Placebo administered QID Device: Treprostinil Ultrasonic Nebulizer Treprostinil ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.
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.	Drug: Inhaled Treprostinil Inhaled treprostinil (6 mcg/breath) administered QID Other Names: Tyvaso Device: Treprostinil Ultrasonic Nebulizer Treprostinil ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Matching placebo inhaled using an ultrasonic nebulizer QID

Drug: Placebo

Placebo administered QID

Device: Treprostinil Ultrasonic Nebulizer

Treprostinil ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.

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.

Drug: Inhaled Treprostinil

Inhaled treprostinil (6 mcg/breath) administered QID

Other Names:

Tyvaso

Device: Treprostinil Ultrasonic Nebulizer

Treprostinil ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.

Outcome Measures

Primary Outcome Measures

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

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Jasper Summit Research, LLC	Jasper	Alabama	United States	35501
3	Arizona Pulmonary Specialists, Ltd.	Phoenix	Arizona	United States	85012
4	St. Joseph's Hospital and Medical Center - Norton Thoracic Institute	Phoenix	Arizona	United States	85013
5	David Geffen School of Medicine at UCLA	Los Angeles	California	United States	90085
6	NewportNativeMD, Inc	Newport Beach	California	United States	92663
7	St. Francis Sleep Allergy & Lung Institute	Clearwater	Florida	United States	33765
8	University of Florida Health at Shands	Gainesville	Florida	United States	32610
9	Ascension St. Vincent's	Jacksonville	Florida	United States	32204
10	University of Florida	Jacksonville	Florida	United States	32209
11	Mayo Clinic Florida	Jacksonville	Florida	United States	32224
12	Ascension Medical Group St. Vincent's Lung Institute	Jacksonville	Florida	United States	33204
13	Pulmonary Disease Specialists, PA d/b/a PDS Research	Kissimmee	Florida	United States	34741
14	Central Florida Pulmonary Group, PA	Orlando	Florida	United States	32803
15	Coastal Pulmonary & Critical Care PLC	Saint Petersburg	Florida	United States	33704
16	University of South Florida Health	Tampa	Florida	United States	33606
17	Emory University Hospital	Atlanta	Georgia	United States	30322
18	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
19	Loyola University Medical Center	Maywood	Illinois	United States	60153
20	The University of Kansas Medical Center	Kansas City	Kansas	United States	66160
21	Norton Pulmonary Specialists	Louisville	Kentucky	United States	40202
22	University of Louisville	Louisville	Kentucky	United States	40202
23	Louisville Pulmonary Care,PLLC	Louisville	Kentucky	United States	40207
24	LSU Health Sciences Center New Orleans	New Orleans	Louisiana	United States	70112
25	Tulane University Medical Center	New Orleans	Louisiana	United States	70112
26	LSU Health Science Center Shreveport	Shreveport	Louisiana	United States	71103
27	Tufts Medical Center	Boston	Massachusetts	United States	02111
28	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
29	University of Michigan Int Med Pulmonary and critical care	Ann Arbor	Michigan	United States	45109
30	Mayo Clinic	Rochester	Minnesota	United States	55902
31	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
32	The Lung Research Center	Chesterfield	Missouri	United States	63017
33	J&L Research, LLC	Saint Louis	Missouri	United States	72032
34	Creighton University Clinical Research Office	Omaha	Nebraska	United States	68124
35	University of New Mexico Health Sciences Center	Albuquerque	New Mexico	United States	87106
36	Northwell Health	New Hyde Park	New York	United States	11040
37	PulmonIx, LLC	Greensboro	North Carolina	United States	27403
38	Pinehurst Medical Clinic, Inc.	Pinehurst	North Carolina	United States	28374
39	Southeastern Research Center	Winston-Salem	North Carolina	United States	27103
40	University of Cincinnati	Cincinnati	Ohio	United States	45267
41	The Ohio State University Wexner Medical Center - Martha Morehouse Medical Pavilion	Columbus	Ohio	United States	43221
42	The Oregon Clinic, PC	Portland	Oregon	United States	97220
43	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
44	Temple Lung Center	Philadelphia	Pennsylvania	United States	19140
45	Medical University of South Carolina	Charleston	South Carolina	United States	29425
46	Clinical Research of Rock Hill	Rock Hill	South Carolina	United States	29732
47	Clinical Trials Center of Middle Tennessee	Franklin	Tennessee	United States	27067
48	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37204
49	Premier Pulmonary Critical Care and Sleep Medicine	Denison	Texas	United States	75020
50	Memorial Hermann-Texas Medical Center	Houston	Texas	United States	77030
51	Metroplex Pulmonary and Sleep Center PA	McKinney	Texas	United States	75069
52	Renovatio Clinical Consultants, LLC	The Woodlands	Texas	United States	77380
53	Intermountain Medical Center	Murray	Utah	United States	84107
54	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
55	Pulmonary Associates of Richmond, Inc.	Richmond	Virginia	United States	23230
56	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226