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Evaluating inhaled treprostinil for progressive pulmonary fibrosis

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)

PHASE3 · United Therapeutics · NCT05943535

This study is testing if inhaled treprostinil can help people with progressive pulmonary fibrosis breathe better and live longer compared to a placebo.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment698 (estimated)
Ages18 Years and up
SexAll
SponsorUnited Therapeutics (industry)
Drugs / interventionsrituximab, methotrexate
Locations153 sites (Birmingham, Alabama and 152 other locations)
Trial IDNCT05943535 on ClinicalTrials.gov

What this trial studies

This Phase 3 clinical trial assesses the safety and efficacy of inhaled treprostinil in patients with progressive pulmonary fibrosis over a 52-week period. Participants will be randomly assigned to receive either inhaled treprostinil or a placebo, with doses titrated based on tolerance. The study will monitor various efficacy outcomes, including lung function and overall survival, alongside safety assessments for adverse events. Participants completing the study may have the option to enter an open-label extension study.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with radiological evidence of pulmonary fibrosis and a diagnosis of progressive pulmonary fibrosis that has worsened despite standard treatment.

Not a fit: Patients with stable pulmonary fibrosis or those who do not meet the specific progression criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve lung function and quality of life for patients with progressive pulmonary fibrosis.

How similar studies have performed: Other studies have shown promise with inhaled therapies for pulmonary conditions, suggesting potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion 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), soluble guanylate cyclase stimulators, or activin signaling inhibitors (sotatercept) 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.
13. Subject has received nerandomilast within 60 days prior to Baseline.

Where this trial is running

Birmingham, Alabama and 152 other locations

+103 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Progressive Pulmonary Fibrosis, Interstitial Lung Disease, Treprostinil, PPF, ILD

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.