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

Sponsor
United Therapeutics (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05255991
Collaborator
(none)
396
2
36

Study Details

Study Description

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
  • 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.

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, Multinational, Phase 3 Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis (TETON-2)
Anticipated Study Start Date :
Sep 1, 2022
Anticipated Primary Completion Date :
Sep 1, 2025
Anticipated Study Completion Date :
Sep 1, 2025

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.

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. Overall Survival at Week 52 [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 [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 [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:
    No
    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.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • United Therapeutics

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    United Therapeutics
    ClinicalTrials.gov Identifier:
    NCT05255991
    Other Study ID Numbers:
    • RIN-PF-303
    • 2021-005881-17
    First Posted:
    Feb 25, 2022
    Last Update Posted:
    Feb 25, 2022
    Last Verified:
    Feb 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Keywords provided by United Therapeutics
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 25, 2022