Overview

Study LTI-401 is an open-label, multicenter study which will evaluate the safety and tolerability of LIQ861 in subjects who have WHO Group 1 & 3 PH.

Eligibility

Inclusion Criteria:

1. An Institutional Review Board (IRB) approved informed consent is signed and dated by the subject prior to any study related activities.
2. Male or Females between 18 years to 75 years of age at Screening. Subjects between 76 and 80 years of age at Screening can be considered for eligibility but will require approval of the Sponsor's MM or designee.
3. If the subject is a female of childbearing potential, then the subject must have a negative pregnancy test result at the Baseline Visit and agrees to practice adequate birth control throughout the duration of the study. If the subject is postmenopausal or has documented surgical sterilization, a pregnancy test and birth control are not necessary. It is the Investigator's responsibility for determining whether the subject has adequate birth control for study participation.
4. Has a confirmed diagnosis of WHO Group 3 PH-ILD based on CT chest imaging performed within 12 months prior to baseline visit, which demonstrates evidence of diffuse parenchymal lung disease and FEV1/FVC (absolute values) >70%. Subjects are required to have evidence of pulmonary hypertension (PH) as demonstrated from right heart catheterization (RHC) within 6 months of the baseline visit with the following documented parameters depending on their lung disease category a) or b).
   1. Subjects may have any form of ILD or combined pulmonary fibrosis and emphysema (CPFE).
   2. Pulmonary vascular resistance (PVR) > 3 Wood Units (WU) and ii) Pulmonary capillary wedge pressure (PCWP) of < 15 mmHg and iii) A mean pulmonary arterial pressure (mPAP) of > 30 mmHg

             OR b. A exploratory subset of subjects with ILD: i) Pulmonary vascular resistance
             (PVR) > 3 Wood Units (WU) and ii) Pulmonary capillary wedge pressure (PCWP) of < 15
             mmHg and iii) A mean pulmonary arterial pressure (mPAP) of > 21 mmHg
          5. Must be able to walk a distance of >125 meters on two six-minute walk tests (6MWTs)
             during the screening and baseline assessments. The variability of the distances
             between the two qualifying 6MWTs must be within 15% of one another, calculated from
             the furthest walk.
          6. Subjects on a chronic medication for underlying lung disease (i.e. pifenidone,
             nintedanib, etc) must be on a stable dose and regimen for > 30 days prior to Baseline
             and planned to continue for the duration of the study at the same dose.
          7. Demonstrates the ability to use the RS00 Model 8 inhaler.
        Exclusion Criteria:
        A Subject is not eligible for inclusion in the study if any of the following criteria
        apply:
          1. Pulmonary hypertension (PH) in the Updated WHO Classification Groups 1, 2, 4, or 5.
          2. Intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue
             that resulted in discontinuation or inability to effectively titrate that therapy.
          3. Received any FDA approved PAH or PH-ILD prostacyclin therapy including: epoprostenol,
             treprostinil, iloprost, beraprost, or IP receptor agonist (selexipag), except for
             acute vasoreactivity testing within 60 days of Screening.
          4. Received any FDA PAH approved oral therapy including: endothelin receptor antagonist
             (ERA), or soluble guanylate cyclase (sGC) stimulator within 60 days of Baseline.
               -  phosphodiesterase type 5 inhibitors (PDE5-I) are permitted if on a stable dose
                  for at least 60 days prior to the right heart catheterization and planned to
                  continue for the duration of the study at the same dose.
               -  PDE5-I are permitted for erectile dysfunction as needed but should be withheld at
                  least 48 hours prior to a scheduled visit.
          5. New type of chronic therapy (including but not limited to oxygen, a different class of
             vasodilator, diuretic, digoxin, and digitalis) for pulmonary hypertension added within
             30 days of Screening and prior to Baseline.
          6. Uncontrolled systemic hypertension as evidenced by persistent, systolic blood pressure
             greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg.
          7. History of hemodynamically significant left-sided heart disease including, but not
             limited to: aortic or mitral valvular disease more than mild, pericardial
             constriction, restrictive or congestive cardiomyopathy with estimated left ventricular
             ejection fraction less than 40%, or symptomatic coronary artery disease (CAD).
          8. Prior atrial septostomy.
          9. Receiving > 8 L/min of oxygen supplementation by any mode of delivery at rest at
             Screening and prior to Baseline.
         10. Serious or life-threatening disease other than conditions associated with PH or ILD.
         11. Therapy with any excluded medications listed in the Investigator's Brochure.
         12. Hypersensitivity or allergy to any of the ingredients of LIQ861 or other clinically
             relevant allergies (clinical relevance per Investigator judgment).
         13. Exacerbation of underlying lung disease or active pulmonary or upper respiratory
             infections within 30 days of Screening and prior to Baseline.
         14. Current RT-PCR confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
             infection or recent history of lab confirmed SARS-CoV-2 infection in previous 30 days
             of Screening and prior to Baseline.
         15. ILD developed from a SARS-CoV-2 infection (ILD should have preceded infection).
         16. Initiation of pulmonary rehabilitation within 12 weeks prior to Screening
             (participants who are stable in the maintenance phase of a program and who will
             continue for the first 16 weeks of the study are eligible).
         17. 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 (i.e.,
             peripheral vascular disease, musculoskeletal disorder, morbid obesity) that would
             likely be the primary limit to ambulation (as opposed to PH).
         18. Acute pulmonary embolism within 90 days of Screening or prior to Baseline.
         19. Stroke or transient ischemic attack (TIA) within six months of Screening or prior to
             Baseline.
         20. Evidence of an active uncontrolled sepsis or systemic infection during Screening.
         21. Pregnant, plans to become pregnant, or lactating.
         22. Participated in an investigational drug or device study within the 30 days prior to
             Screening.
         23. In the opinion of the Investigator, significant use of any inhaled tobacco/marijuana
             products or significant recent history of drug abuse at the time of informed consent.
         24. Subject has severe hepatic impairment as evidenced by any history of ascites AND
             encephalopathy.
         25. Renal impairment (eGFR < 40). (Appendix 5).
         26. Severe concomitant illness limiting life expectancy (≤ 6 months) or listed "active"
             for lung transplantation.
         27. Currently on hospice status or planned hospice status in the next 6 months.
         28. Known anaphylactoid reaction or hypersensitivity allergy to intravenous iodinated
             contrast media.