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Multinational Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis (TETON-2)

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ClinicalTrials.gov Identifier: NCT05255991
Recruitment Status : Recruiting
First Posted : February 25, 2022
Last Update Posted : November 18, 2022
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Brief Summary:
Study RIN-PF-303 is a multinational study 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-303 is a multinational, 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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, Multinational, Phase 3 Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis (TETON-2)
Actual Study Start Date : October 4, 2022
Estimated Primary Completion Date : June 2025
Estimated Study Completion Date : June 2025


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 Name: Tyvaso

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




Primary Outcome Measures :
  1. Change in Absolute FVC from Baseline to Week 52 [ Time Frame: 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 :
  1. Time to Clinical Worsening [ Time Frame: 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.

  2. Time to First Acute Exacerbation of IPF [ Time Frame: 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.

  3. Overall Survival at Week 52 [ Time Frame: Baseline to Week 52 ]
    Vital status will be assessed for all subjects at Week 52, including those who discontinue the study prematurely or who withdraw consent.

  4. Change in % Predicted FVC from Baseline to Week 52 [ Time Frame: 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.

  5. Change in K-BILD Questionnaire Score from Baseline to Week 52 [ Time Frame: 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05255991


Contacts
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Contact: United Therapeutics Global Medical Information 919-485-8350 clinicaltrials@unither.com

Locations
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Sponsors and Collaborators
United Therapeutics
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Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT05255991    
Other Study ID Numbers: RIN-PF-303
2021-005881-17 ( EudraCT Number )
First Posted: February 25, 2022    Key Record Dates
Last Update Posted: November 18, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by United Therapeutics:
Treprostinil
IPF
ILD
Additional relevant MeSH terms:
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Lung Diseases
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Lung Diseases, Interstitial
Fibrosis
Pathologic Processes
Respiratory Tract Diseases
Treprostinil
Antihypertensive Agents