18 Years and up
Accepting Healthy Volunteers?
1. Subject voluntarily gives informed consent to participate in the study.
2. Males and females aged 18 years or older at the time of informed consent.
a. Females of reproductive potential must be non-pregnant (as confirmed by a urine
pregnancy test at screening) and non-lactating, and will: i. Either abstain from
intercourse (when it is in line with their preferred and usual lifestyle), or ii. Use
two medically acceptable, highly-effective forms of contraception for the duration of
study, and at least 30 days after discontinuing study drug.
b. 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.
3. The subject has a confirmed diagnosis of WHO Group 3 PH based on CT imaging, which
demonstrates evidence of diffuse parenchymal lung disease performed within 6 months
prior to randomization. Subjects may have any form of ILD or CPFE.
4. Subjects are required to have a right heart catheterization (RHC) within one year
prior to randomization with the following documented parameters:
1. Pulmonary vascular resistance (PVR) > 3 Wood Units (WU) and
2. A pulmonary capillary wedge pressure (PCWP) of < 15 mmHg and and
3. A mean pulmonary arterial pressure (mPAP) of ≥ 25 mmHg
5. Baseline 6MWD ≥ 100 meters
6. Subjects on a chronic medication for underlying lung disease (ie, pirfenidone,
nintedanib, etc) must be on a stable and optimized dose for ≥ 30 days prior to
randomization. Subjects receiving pirfenidone or nintedanib must have been receiving
treatment for at least 90 days and on a stable dose for at least 30 days prior to
7. 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.
8. Subjects with connective tissue disease (CTD) must have a Baseline FVC of < 70%.
1. The subject has a diagnosis of pulmonary arterial hypertension (PAH) or PH for reasons
other than WHO Group 3 PH-ILD as outlined in inclusion criterion 3.
2. 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.
3. The subject has received any PAH approved therapy including: prostacyclin therapy
(i.e., epoprostenol, treprostinil, iloprost, or beraprost; except for acute
vasoreactivity testing), IP receptor agonist (selexipag), endothelin receptor
antagonist (ERA), phosphodiesterase type 5 inhibitor (PDE-5I), or soluble guanylate
cyclase (sGC) within 60 days of randomization.
4. The subject has evidence of clinically significant left-sided heart disease as defined
1. PCWP > 15 mmHg
2. Left ventricular ejection fraction < 40%.
Note: Subjects with abnormal left ventricular function attributable entirely to
impaired left ventricular filling due to the effects of right ventricular overload
(i.e., right ventricular hypertrophy and/or dilatation) will not be excluded.
5. The subject is receiving > 10 L/min of oxygen supplementation by any mode of delivery
at rest at Baseline.
6. Current use of any inhaled tobacco/marijuana products or significant history of drug
abuse at the time of informed consent.
7. Exacerbation of underlying lung disease or active pulmonary or upper respiratory
infection within 30 days of randomization.
8. Initiation of pulmonary rehabilitation within 12 weeks prior to the randomization.
9. In the opinion of the Investigator, the subject has any condition that would interfere
with the interpretation of study assessments or has any disease or condition (ie,
peripheral vascular disease, musculoskeletal disorder, morbid obesity) that would
likely be the primary limit to ambulation (as opposed to PH).
10. Use of any investigational drug/device, or participation in any investigational study
with therapeutic intent within 30 days prior to randomization.
11. Severe concomitant illness limiting life expectancy (< 6 months).
12. Acute pulmonary embolism within 90 days of randomization.