Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)

Interstitial Lung Disease Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Multinational, Phase 3 Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05943535
• Other study ID #: RIN-PF-305
• Status: Recruiting
• Phase: Phase 3
• Start date: October 30, 2023
• Est. completion date: November 2027

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-305 is designed to evaluate the safety and efficacy of inhaled treprostinil in subjects with progressive pulmonary fibrosis (PPF) over a 52-week period.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 698
• Est. completion date: November 2027
• Est. primary completion date: November 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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:

1. 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), 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 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.

Related Conditions & MeSH terms

• 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	CIC Mauricie inc.	Québec	Quebec
United States	University of New Mexico	Albuquerque	New Mexico
United States	UAB Lung Health Center	Birmingham	Alabama
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-Nexus	Charleston	South Carolina
United States	The Lung Research Center, LLC	Chesterfield	Missouri
United States	Rush University Medical Center Outpatient Pulmonary Clinic	Chicago	Illinois
United States	UI Health Hospital	Chicago	Illinois
United States	Prisma Health Pulmonology-Richland	Columbia	South Carolina
United States	The Ohio State University Wexner Medical CEnter	Columbus	Ohio
United States	Christopher King, MD	Falls Church	Virginia
United States	Clinical Trials Center of Middle Tennessee, LLC	Franklin	Tennessee
United States	PulmonIx LLC	Greensboro	North Carolina
United States	East Carolina University	Greenville	North Carolina
United States	The University of Texas Health Science Center at Houston, McGovern Medical School	Houston	Texas
United States	Ascension Medical Group St. Vincent's Lung Institute	Jacksonville	Florida
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	StatCare Pulmonary Consultants, PLLC	Knoxville	Tennessee
United States	University of Kentucky	Lexington	Kentucky
United States	University of Louisville Healthcare Outpatient Research Clinic	Louisville	Kentucky
United States	University Hospital and UW Health Clinics	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	McKinney	Texas
United States	University of Minnesota Health Clinical Research Unit (CRU)	Minneapolis	Minnesota
United States	Northwell Health	New Hyde Park	New York
United States	Tulane Medical Center	New Orleans	Louisiana
United States	NewportNativeMD, Inc.	Newport Beach	California
United States	Infinity Medical Center	North Dartmouth	Massachusetts
United States	University of California Irvine Medical Center	Orange	California
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Norton Thoracic Institute	Phoenix	Arizona
United States	Pulmonary Associates of Richmond, Inc.	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Beaumont Hospital, Royal Oak	Royal Oak	Michigan
United States	University of Utah Health	Salt Lake City	Utah
United States	Paradigm Clinical Research	San Diego	California
United States	Adventist Healthcare White Oak Medical Center	Silver Spring	Maryland
United States	Stanford University Medical Center	Stanford	California
United States	Stony Brook Advanced Specialty Care	Stony Brook	New York
United States	TGH/USF Center for Advanced Lung Disease and Lung Transplant	Tampa	Florida
United States	Georgetown University Hospital	Washington	District of Columbia

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 First Clinical Worsening	Clinical worsening is monitored from randomization until 1 of the following criteria are 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 ILD	An exacerbation of ILD 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 race, 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 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