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

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.