Clinical trial NCT05943535: Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Progressive Pulmonary Fibrosis
Interstitial Lung Disease
Keywords: Treprostinil
PPF
ILD
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-07-13
Enrollment: 698
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Absolute FVC from Baseline to Week 52
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: Time to First Clinical Worsening
timeFrame: Baseline to Week 52
measure: Time to First Acute Exacerbation of ILD
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: UAB Lung Health Center
state: Alabama
city: Phoenix
country: United States
facility: Norton Thoracic Institute
state: Arizona
city: Los Angeles
country: United States
facility: Peter Morton Medical Building
state: California
city: Newport Beach
country: United States
facility: NewportNativeMD, Inc.
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Health Medical Center
state: California
city: San Diego
country: United States
facility: Paradigm Clinical Research
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Jacksonville
country: United States
facility: Ascension Medical Group St. Vincent's Lung Institute
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Tampa
country: United States
facility: TGH/USF Center for Advanced Lung Disease and Lung Transplant
state: Florida
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital, Clinical Research Unit
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center Outpatient Pulmonary Clinic
state: Illinois
city: Chicago
country: United States
facility: UI Health Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Healthcare Outpatient Research Clinic
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Asthma and 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: North Dartmouth
country: United States
facility: Infinity Medical Center
state: Massachusetts
city: Royal Oak
country: United States
facility: Beaumont Hospital, Royal Oak
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Health Clinical Research Unit (CRU)
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Chesterfield
country: United States
facility: The Lung Research Center, LLC
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: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine, New York-Presbyterian Hospital
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Advanced Specialty Care
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greensboro
country: United States
facility: PulmonIx LLC
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical CEnter
state: Ohio
city: Toledo
country: United States
facility: Mercy Health St.Vincent Medical Center LLC
state: Ohio
city: Hershey
country: United States
facility: Pennsylvania State Hershey Medical Center and College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina-Nexus
state: South Carolina
city: Columbia
country: United States
facility: Prisma Health Pulmonology-Richland
state: South Carolina
city: Franklin
country: United States
facility: Clinical Trials Center of Middle Tennessee, LLC
state: Tennessee
city: Knoxville
country: United States
facility: StatCare Pulmonary Consultants, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Vanderbilt Lung Institute
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center-Advanced Lung Clinic
state: Texas
city: Houston
country: United States
facility: Houston Methodist Outpatient Center
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston, McGovern Medical School
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
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: Christopher King, MD
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond, Inc.
state: Virginia
city: Madison
country: United States
facility: University Hospital and UW Health Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Mar Del Plata
country: Argentina
facility: Instituto Ave Pulmo - Fundacion enfisema
state: Buenos Aires
city: Río Cuarto
country: Argentina
facility: Instituto Medico Rio Cuarto
state: Cordoba
city: Rosario
country: Argentina
facility: Sanatorio Parque de Rosario - Consultorios Externos
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Investigaciones en Patologias Respiratorias
state: Tucuman
city: San Miguel De Tucumán
country: Argentina
facility: CIMER-Centro Integral de Medicina Respiratoria
state: Tucumán
city: Ciudad Autonoma de Buenos aires
country: Argentina
facility: CINME Centro de Investigaciones Metabolicas
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Fundación Respirar
city: Cordoba
country: Argentina
facility: Instituto de Medicina Respiratoria
city: Córdoba
country: Argentina
facility: Sanatorio Allende Cerro
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Health Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Health-Monash Medical Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Midland
country: Australia
facility: Institute for Respiratory Health - Midland
state: West Australia
city: Nedlands
country: Australia
facility: Institute for Respiratory Health
state: Western Australia
city: Aalst
country: Belgium
facility: AZORG
city: Brussels
country: Belgium
facility: CUB Hopital Erasmde
city: Brussels
country: Belgium
facility: Cliniques Universitaires St.-Luc
city: Liège
country: Belgium
facility: CHU de Liège
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: Montreal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
state: Quebec
city: Québec
country: Canada
facility: CIC Mauricie inc.
state: Quebec
city: Curicó
country: Chile
facility: Centro de Investigacion Curico
state: Maule
city: Santiago
country: Chile
facility: CEC Centro Estudios Clinicos
state: Region Metropolitana
city: Santiago
country: Chile
facility: Fundacion Medica San Cristobal
state: Region Metropolitana
city: Santiago
country: Chile
facility: Biocinetic Ltda.
state: Region Metropolitana
city: Quillota
country: Chile
facility: Centro Respiratorio Integral LTDA. (CENRESIN)
state: Valparaiso
city: Viña Del Mar
country: Chile
facility: Centro de Investigación de Enfermedades Respiratorias e Inmunológicas (CIERI)
state: Valparaíso
city: Bobigny
country: France
facility: Hôpital Avicennes
city: Bron
country: France
facility: Hospices civils de Lyon - Hôpital Louis Pradel
city: Caen
country: France
facility: CHU Caen Normandie
city: Marseille
country: France
facility: Assistance Publique Hôpitaux de Marseille - centre Hospitalier Régional de Marseille
city: Tours Cedex 9
country: France
facility: Centre Hospitalier Régional Universitaire de Tours
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Rabin Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Eunpyeong St. Mary's Hospital
city: Christchurch
country: New Zealand
facility: Canterbury Respiratory Research Group
state: Canterbury
city: Auckland
country: New Zealand
facility: Aotearoa Clinical Trials Trust- Middlemore Hospital
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Medical Foundation Kaohsiung Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
Study officials:
References: