Inclusion Criteria:
1. Male or female age 22 to < 85 years old. 2. Provides signed informed consent for study participation. 3. Diagnosis of any form of advanced Interstitial Lung Disease or Combined Pulmonary
Fibrosis and Emphysema (CPFE) at any time, based on clinical, pulmonary function,
serological, and Computed Tomography (CT) radiologic evidence (which demonstrates
evidence of moderate to severe diffuse parenchymal lung disease)
4. A prior Right Heart Catheterization (RHC) at any time before SV that demonstrates PH
with a Pulmonary Vascular Resistance (PVR) >2.0 Wood Units (WU), a mean Pulmonary
Arterial Pressure (mPAP) > 20 mmHg, and a Pulmonary Capillary Wedge Pressure (PCWP) ≤
15 mmHg. A PCWP >15 mmHg is not exclusionary if a left ventricular end diastolic
pressure (LVEDP) is available and is ≤ 15 mmHg by left heart catheterization AND/OR
Previous Echocardiography with an intermediate/high probability of PH (European
Society of Cardiology definition)
5. New York Heart Association (NYHA) functional class II-IV. 6. Self-reported use of long-term O2 therapy (LTOT) less than or equal to 10 L/minute at
rest and while exercising, defined as use for at least 12 hours per day for at least
30 days prior to SV. 7. Is willing to comply with treatment with iNO and procedures including using the 3P-100
device and wearing a nasal cannula for at least 4 hours at V1. 8. Is able to wear a 3P-100 device while sitting and ambulating intermittently in the
clinic area for at least 30 minutes during SV. 9. Women of child-bearing potential must agree to use the methods of birth control
indicated in Appendix 1 from consent through the Telephone Call at V1 +1 Day.
Exclusion Criteria:
1. History or diagnosis by Investigator evaluation during SV of World Health Organization
(WHO) Group I, II, IV, or V PH. 2. NYHA class IV patients who are medically unfit to participate i.e., are constantly
breathless at rest or have frequent symptoms of chest pain or syncope at rest or with
activity. 3. History or diagnosis of acute or chronic left heart failure at any time as evidenced
by one or more of the following:
1. PCWP > 15 mmHg on a previous RHC (unless LVEDP is ≤15 mmHg) AND/OR LVEDP >15 mmHg
by left heart catheterization. 2. Previous echocardiographic findings of left ventricular systolic dysfunction with
ejection fraction < 40%
3. Cardiogenic pulmonary edema. 4. History of left heart failure (Prior or current use of medications given solely
for the treatment of systemic hypertension are allowed)
4. History of hereditary methemoglobinemia. 5. History of the following cardiovascular conditions:
1. Stenting or Coronary Artery Bypass Graft (CABG) within 60 days prior to SV. 2. Myocardial infarction within the 60 days prior to SV. 3. Unstable angina pectoris in the 60 days prior to SV. 4. Intermittent atrial fibrillation, supraventricular tachycardia, and serious
ventricular arrhythmias (e.g., ventricular tachycardia) within 60 days prior to
SV. Ablated atrial flutter or Wolf-Parkinson-White (WPW) bypass tract conduction
are not exclusionary. 5. Cerebrovascular accident within the 60 days prior to SV. 6. Has within 30 days prior to SV or during the Screening period. 1. Participated in any clinical study involving an investigational drug,
investigational biologic, or investigational device. 2. Required unplanned hospitalization for any reason. 3. Had an exacerbation of ILD requiring administration of oral or parenteral
antibiotic. 7. Has within the 30 days prior to SV or during the Screening period required initiation
or changes in the regimen (including agents, dose, and frequency) of medications
prescribed for the treatment of ILD, including but not limited to immunosuppressive /
immunomodulatory medications, systemic oral or parenteral corticosteroids, and
monoclonal antibodies. 8. Has within 30 days prior to SV, or any time during Screening period taken one or more
of the following medications or supplements chronically:
1. Oral, inhaled, or parenteral medications for the treatment of Pulmonary Arterial
Hypertension (PAH) irrespective of the route of administration including, but not
limited to,
- - high dose calcium channel blockers.
- - prostacyclin analogues.
- - prostacyclin receptor agonists (e.g., selexipag)
- phosphodiesterase type 5 (PDE5) inhibitors (e.g., sildenafil) if the subject
is on inhaled treprostinil.
- - endothelin receptor antagonists.
2. Inhaled treprostinil (approved for PH-ILD), if the subject is on a PDE5 inhibitor
for PH-ILD. Note: Inhaled treprostinil is not exclusionary as a monotherapy, however, the
concurrent use of both a PDE5 inhibitor (e.g., sildenafil) and inhaled
treprostinil is exclusionary. The use of either a PDE5 inhibitor or inhaled
treprostinil will be allowed if both conditions are met:
- - The PDE5 inhibitor or inhaled treprostinil was started more than 30 days
prior to the SV.
- - There have been no changes in the PDE5 inhibitor or inhaled treprostinil
dosage within 30 days prior to the SV.
3. Nitrates, regardless of route of administration. 4. Supplements containing L-arginine. 5. Agents or medications capable of inducing methemoglobinemia where any of the
SV/V1 metHb average measurements via co-oximeter are > 3.5%
Subjects should not be weaned from these therapies for the purpose of enrollment.
9. Is breastfeeding or lactating at the time of SV or intends to breastfeed at any time
during their participation in the study. 10. Has one of the following in their medical record or through testing performed:
1. Positive urine pregnancy test at SV or on V1 (results of the test are to be known
prior to initiation of the iNO)
2. Hemoglobin < 10 g/dL (100 g/L) within 30 days of SV. 3. HbA1c > 10% within 30 days of SV. 4. Glomerular Filtration Rate (GFR) < 30 mL/min/1.73 m2 , calculated using the
Creatinine Clearance (CKD-EPI) calculation method within 30 days of SV. 5. Methemoglobin > 3.5% at SV or V1 via co-oximeter measurements. 6. Thrombocytopenia with a platelet count < 50 x 103 /µL (< 50 X 109/L) within 30
days of SV. 11. Has any condition at SV/V1 that could constitute a safety concern during participation
in the study or could interfere with the subject's ability to comply with adherence to
iNO, including but not limited to:
1. Uncontrolled systemic hypertension defined by systolic Blood Pressure (BP) > 180
mmHg and/or a diastolic BP > 110 mmHg measured manually after 20 minutes at rest
on prescribed resting O2. 2. History of alcohol or substance abuse within the past 365 days prior to SV. Drugs
documented as prescribed by a physician or use of edible marijuana if legal in
the state of residence may be allowed with approval of the Medical Monitor.
Smoking and vaping of any substance is prohibited (e.g., nicotine or marijuana)
3. History of poor compliance with prior clinical studies. 4. Acute or chronic physical impairment (other than dyspnea due to ILD) (e.g.,
neurologic, musculoskeletal, or orthopedic disorder, or dependence on mobility
aids such as a cane or walker) that would limit the ability to carry and operate
the 3P-100 device together with their O2 system. 5. Severe right heart failure confirmed by the investigator as evidenced by two or
more of the following: elevated jugular venous pressure, peripheral edema,
hepatic congestion and/or ascites. 6. Other known coagulopathies. 12. Is a relative of Third Pole, the Contract Research Organization (CRO) or other vendor,
or investigational site/institutional personnel. 13. Has during the SV one or more of the following results:
1. Forced Expiratory Volume (FEV1)/Forced Vital Capacity (FVC) ratio < 0.7 except
for CPFE. 2. FVC < 40% predicted
