A Multinational Phase 2, Randomized, Double-Blinded, Placebo-Controlled, Multiple-Dose Study to Evaluate the Safety and Efficacy of Mirivadelgat, an Aldehyde Dehydrogenase 2 Activator, in Patients With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
The goal of this clinical trial is to see if mirivadelgat will work in participants with Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD). It will also learn about the safety of mirivadelgat. The main question it aims to answer is if mirivadelgat will improve pulmonary vascular resistance (PVR). Pulmonary vascular resistance is a way to measure blood flow in the lungs. Researchers will compare mirivadelgat to a placebo (a look-alike capsule that contains no drug) to see if mirivadelgat works to improve the symptoms of PH-ILD. The symptoms of PH-ILD that are being looked at are exercise tolerance, heart function, and general well-being. Participants will: Take mirivadelgat or a placebo once a day for 12 weeks Visit the clinic once every 4 weeks for checkups and tests Receive phone calls every one or two weeks to check on how things are going
• A clinical diagnosis of PH-ILD.
• Participant voluntarily gives informed consent.
• Male or female participants aged between 18 and 85 years at the time of signing informed consent.
• Participants must agree to practice protocol-defined birth control during the study period, unless they meet criteria for not being of childbearing potential.
‣ Male participants with female partners of childbearing potential must practice protocol- defined birth control for the duration of treatment and at least 96 hours after discontinuing the IP.
⁃ Female participants 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).
⁃ Female participants not of childbearing potential (as defined below) are eligible for enrolment without contraception requirements:
⁃ 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
• Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR
• Have a congenital or acquired condition that prevents childbearing.
• The participant 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 participant can have other findings (e.g., emphysema) if this is not the predominant feature on the scan.
• Participants 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 \[if PVR ≥6.25 Wood units\] Note: If a reliable PCWP cannot be obtained, left ventricular end-diastolic pressure (LVEDP), measured via left heart catheterization (LHC), will be acceptable, with the same numerical thresholds as the PCWP criterion: LVEDP of ≤12 mmHg \[if PVR ≥4 to \<6.25 Wood units\], or LVEDP ≤15 mmHg
⁃ A mean pulmonary arterial pressure (PAP) of \>20 mmHg.
• Participants must have a 6-minute walk distance ≥100 meters and ≤500 meters at the Screening Visit (Visit 1).
• Participants agree to a repeat RHC, Chest CT, and MRI prior to study completion.
• Participants 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.
⁃ Participants on supportive medications (e.g., inhalers for asthma) must be on stable doses for ≥30 days prior to screening.
⁃ In the Investigator's opinion, the participant must be able to consent for themselves and communicate with local staff using interpreters if necessary. Participants must agree to attend all study visits and be contactable through a cellular device or landline.
⁃ Participants must have clinical laboratory values within normal ranges or \<1.5 times the upper limit of normal (ULN) as specified by the testing laboratory.
⁃ Participants must meet the following requirements for the pulmonary function test (PFT) at screening:
∙ Forced vital capacity (FVC) \<90% of predicted
‣ Diffusion capacity of carbon monoxide (DLCO) \<70% of predicted, or \<70% of predicted corrected for hemoglobin (Hb), if correction is required. (Correction applies if Hb value is ≥25% and ≤90% of normal.) Note: DLCO must be determined locally at screening, using American Thoracic Society (ATS) standards. Hemoglobin correction should reference ATS normal values: Men = 14.6 g/dL, Women = 13.4 g/dL.
⁃ Negative serology test for hepatitis B surface antigen and hepatitis C antibody at Screening Visit.