TEPH: Telaglenastat Efficacy in Pulmonary Hypertension

Inclusion Criteria

• •1. Male or female age 18-75 years old.
• •2. Able to provide written informed consent.
• •3. Able to comply with study procedures, able to undergo cardiac catheterization and exercise testing.
• •4. Patients will be identified with PH Group 1-4 PH by an expert clinician in the UPMC Comprehensive Care Center for Pulmonary Hypertension.
• •5. For Group 1, 3, and 4 PH, prior right heart catheterization (RHC) should show documented diagnosis of precapillary PH at mean pulmonary arterial pressure (mPAP \> 20 mm Hg, PCWP \< 15 mm Hg, and PVR \> 4 WU) within 1 year of randomization. If patient doesn't have RHC within 1 year, we will repeat RHC at baseline visit. For Group 2 PH, prior right heart catheterization (RHC) should show mean pulmonary arterial pressure mPAP \> 20 mm Hg and PVR \> 4 WU within one year of randomization. If patient don't have RHC within 1 year we will repeat RHC at baseline visit.
• •6. Minimum pulmonary vascular resistance (PVR) of \> 4 Wood units by RHC at screening within last 6 months on at least one month of stable medical therapy.
• •7. Symptomatic PH classified as WHO functional class II or III.
• •8. Body mass index (BMI) 18 to 40 kg/m² at Screening. If BMI is \> 35 kg/m², subject chest circumference should be \< 65 inches (165 cm).
• •9. 6-minute walk distance (6MWD) ≥ 100 meters (m) and \< 550 m at screening.
• •10. For Group 1 PH, patients on SOC medical treatment for PH with vasodilators or Sotatercept are required to have been receiving a stable dose for at least 3 months before undergoing randomization.
• •11. For Group 2 PH-HFpEF: Documented transthoracic echocardiogram or cardiac MRI with LV ejection fraction \> 50% within 6 months of enrollment, along with meeting at least one of the three criteria by echocardiographic/MRI: (1) Diastolic dysfunction, (2) Left atrial enlargement (LA diameter \> 3.6 cm), or (3) Prior right heart catheterization data indicating PCWP \> 15 mm Hg. Stable heart failure therapy for at least 30 days.
• •12. For Group 3 PH-ILD, documented diagnosis of interstitial lung disease (diffuse parenchymal lung disease) by high resolution lung CT scan within 6 months of randomization. Patients with Group 3 PH with connective tissue disease should have confirmed baseline FVC \< 70% within 6 months of randomization. For subjects with a history of lobectomy or pneumonectomy, and for whom there are no population-based normalization methods, assessment based on residual lung volume will be permitted to assess eligibility. Patients receiving drug treatment (i.e., pirfenidone or nintedanib) for their underlying lung disease or pulmonary hypertension (i.e., inhaled Treprostinil) should receive a stable dose for at least 30 days before undergoing randomization.
• •13. For Group 4 PH (CTEPH) eligible patients will have V/Q scan or CT scan with contrast demonstrating chronic thromboembolic disease in the pulmonary vasculature at least 6 months after most recent pulmonary embolus and with right heart catheterization within one year of enrollment. If patient doesn't have RHC within 1 year, we will repeat RHC at baseline visit. Eligible patients will include those with inoperable CTEPH or at least 6 months post-surgery with persistent thromboembolic disease. Patients receiving approved therapies for pulmonary hypertension are required to have been receiving a stable dose for at least 30 days before undergoing randomization.
• •14. Women of childbearing potential must be willing and able to practice medically acceptable effective contraception during the study and continuing contraception for 30 days after their last dose of study drug. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential. Men who are not sterile must also agree to use contraception.