Inclusion Criteria:
1. A clinical diagnosis of PH-ILD.
2. Subject voluntarily gives informed consent.
3. Subjects aged between 18 and 85 years at the time of signing informed consent.
4. Subjects must agree to practice protocol-defined birth control during the study period.
* Males with a partner of childbearing potential must practice protocol-defined birth control for the duration of treatment and at least 96 hours after discontinuing the IP.
* Female subjects of childbearing of potential (including those \<1-year post menopausal) must practice protocol-defined birth control during the conduct of the study and for 30 days after the last dose of IP (males only during exposure to IP).
* Women not of childbearing potential are defined as:
1. Post-menopausal women (at least 12 months with no menses without an alternative medical cause); in women \<45 years of age, a high follicle-stimulating hormone (FSH) level in the post-menopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy; OR
2. Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR
3. Have a congenital or acquired condition that prevents childbearing.
5. The subject has a confirmed diagnosis of any form of interstitial lung disease based on high resolution computed tomography (HRCT) of the chest within 180 days prior to screening or at screening or a historical surgical biopsy (or other appropriate tissue sampling (e.g., cryobiopsy). The subject can have other findings (e.g., emphysema) if this is not the predominant feature on the scan.
6. Subjects have undergone RHC during the screening period with the following documented parameters:
* Pulmonary vascular resistance (PVR) ≥4 Wood units and
* Pulmonary capillary wedge pressure (PCWP) of ≤12 mmHg \[if PVR ≥4 Wood units to \<6.25 Wood units\] or PCWP ≤15 mmHg \[if PVR ≥6.25 Wood units\] (a left ventricular end diastolic pressure \[LVEDP\] will be acceptable if a reliable PCWP cannot be obtained) and
* A mean pulmonary arterial pressure (PAP) of \>20 mmHg.
7. Subjects must have a baseline 6-minute walk distance ≥100 meters and ≤500 meters.
8. Subjects agree to a repeat RHC, Chest CT, and MRI prior to study completion.
9. Subjects on chronic treatment for underlying lung disease (i.e., nintedanib or pirfenidone or immunosuppressive agents etc.) must be on a stable/optimized dose for ≥30 days prior to screening and have been receiving treatment for ≥90 days.
10. Subjects on supportive medications (e.g., inhalers for asthma) must be on stable doses for ≥30 days prior to screening.
11. In the Investigator's opinion, the subject must be able to consent for themselves and communicate with local staff using interpreters if necessary. Subjects must agree to attend all study visits and be contactable through a cellular device or landline.
12. Subjects must have clinical laboratory values within normal ranges or \<1.5 times the upper limit of normal (ULN) as specified by the testing laboratory.
13. Pulmonary function test (PFT) showing a percent predicted forced vital capacity (FVC) \<70% of predicted and diffusion capacity of carbon monoxide (DLCO) \<70% corrected for hemoglobin (Hb) value ≥25% and ≤90% at screening (DLCO determined locally must be \<70%) using the American Thoracic Society (ATS) standards.
14. Subjects with a prior diagnosis of connective tissue diseases, specifically systemic sclerosis (scleroderma), systemic lupus erythematosus, Sjogren's disease, polymyositis/dermatomyositis/antisynthetase syndrome, rheumatoid arthritis can be included in the study, but no more than 20% of total subjects.
15. Negative serology test for hepatitis B surface antigen and hepatitis C antibody at Screening Visit.
Exclusion Criteria:
Medical Conditions
1. Subject has another concomitant diagnosis of pulmonary hypertension not otherwise considered to be PH-ILD. This would include and is not limited to the concomitant presence of thromboembolic disease, untreated/inadequately treated obstructive sleep apnea, human immunodeficiency virus (HIV), methamphetamine or anorexigenic drug use, and other conditions of the WHO Group 1, 2, 4, and 5 classifications.
2. Subject has evidence of clinically significant left-sided heart disease within 6 months as defined by:
* Left ventricular ejection fraction \<40% as assessed by echocardiography.
* More than mild left-sided valvulopathy (e.g., worse than mild mitral stenosis or regurgitation and worse than mild aortic stenosis or regurgitation).
* LVEDP or PCWP \>15 mmHg (or \>12 mmHg if PVR ≥4 to 6.25 Wood units).
3. Subjects must NOT have 3 or more of the following left ventricular disease/dysfunction risk factors at screening:
* Body mass index (BMI) ≥30 kg/m2.
* Uncontrolled diabetes, HbA1C \>9.5%, urine glycosuria \>1.0 g/dl, or presence of diabetic ketoacidosis
* History of significant coronary disease within 6 months of screening as demonstrated by any of the following:
1. History of myocardial infarction or acute coronary syndrome (unstable angina), or
2. Percutaneous coronary intervention or percutaneous transluminal angioplasty, or previous coronary artery bypass graft, or
3. Evidence of coronary artery disease (\>50% stenosis in at least one major coronary artery) or abnormal nuclear stress test.
4. The subject is receiving \>10 L/min of oxygen supplementation by any mode of delivery at rest.
5. The subject has received any PH-approved therapy, including phosphodiesterase type 5 inhibitor, soluble guanylate cyclase inhibitor, endothelin receptor antagonist, or parenteral or oral prostacyclin therapy (excluding vasoreactivity testing) within 60 days of randomization or 5 half-lives. Inhaled prostacyclin (e.g., inhaled treprostinil) on stable doses for ≥30 days prior to screening will be allowed irrespective of local approval (as per ESC/ERS 2022).
6. Use of any potent inhibitors and potent inducers of cytochrome P450 3A4 (CYP3A4) (e.g., boceprevir, cobicistat, danoprevir and ritonavir, elvitegravir and ritonavir, grapefruit juice, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole, ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, telithromycin, troleandomycin, voriconazole, clarithromycin, idelalisib, nefazodone, nelfinavir, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort).
7. Recent exacerbation of underlying lung disease or active pulmonary/upper respiratory tract infection within 4 weeks of randomization.
8. Any current active malignancy (this does not include localized cancers such as basal or squamous cell carcinoma of the skin). Any history of malignancy that is likely to result in mortality or require significant medical or surgical intervention within the following year.
9. Chronic kidney disease Stage IV or greater (i.e., eGFR ˂30 mL/min/1.73m2) or evidence of acute kidney injury.
10. The subject has a history of congenital heart disease irrespective of any prior treatment of surgical intervention
11. Use of tobacco, e-cigarette, nicotine, or marijuana products or significant history of drug or alcohol abuse within 6 months of screening.
12. Acute pulmonary embolism within 90 days of screening.
13. Participation in pulmonary rehabilitation within 90 days of screening.
14. Prior or concurrent use of any investigation drug/device/therapy or participation in any investigational study with therapeutic intent within 30 days or 5 half-lives, whichever is longer before the first dose of the IP.
15. BMI ≥40 kg/m2.
16. Uncontrolled hypertension as evidenced by systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg during the screening period. Subjects who fail screening due to high blood pressure can be re-screened once, after their antihypertensive medicines have been adjusted and doses have been stable for at least 4 weeks.
17. Concomitant disease that confers a life expectancy of \<6 months at screening.
18. The Investigator judges that the subject will be unable to fully participate in the study and complete it for any reason, including inability to comply with the study procedures and treatment of addiction or any other relevant medical or psychiatric conditions.
19. High likelihood of lung transplantation (in the opinion of the Investigator) within 4 months after randomization.
20. History of liver dysfunction, including subjects with moderate (Child-Pugh B) or severe (Child Pugh C) impairment or disordered coagulation.
21. Female subjects who are pregnant or breastfeeding.
22. Worse than mild untreated sleep apnea (5-14.9 events/hour). Treated sleep apnea is permitted.
Other Exclusions
23. History of allergic or anaphylactic reaction to mirivadelgat or to any component of the excipient.
24. Previous exposure to mirivadelgat.
Diagnostic Assessments
25. The following laboratory parameters are excluded:
* Hemoglobin \<10 g/dL (100 g/L).
* White blood cells (WBC) \<3000/µL (\<3000/mm3).
* Platelet count \<70,000/µL (70,000/mm3).
* Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2 or evidence of acute kidney injury.
