HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction

Phase 1b/2, Multicenter, Double-Blind, Placebo-Controlled, Multiple Dose Study Assessing the Pharmacokinetics, Safety, Pharmacodynamics, and Efficacy of HS235 in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction

Study of HS235 in Overweight and Obese Participants with Combined Pre and Post-Capillary Pulmonary Hypertension due to Heart Failure with Preserved Ejection Fraction

Inclusion: Participants are eligible to be included in the study only if they meet at least all the following criteria:; Male or female, ≥ 18 years of age; [Sub-population A only - using a remote PAP sensor]- Ambulatory PAP monitoring (e.g., CardioMEMS™ HF System or Cordella™ HF System) implanted in the course of standard of care at least 90 days before Screening; Hemodynamic evidence of PH with:; mPAP ≥ 25 mm Hg, as measured by the ambulatory PAP monitoring system in supine position by the averaged 7-day values (weekly average) 2 weeks and 1 week before Randomization AND,; dPAP ≥ 15 mm Hg, as measured by the ambulatory PAP monitoring system in supine position by the averaged 7-day values (weekly average) 2 weeks and 1 week before Randomization; Hemodynamic evidence of pre-capillary PH based on presence of PVR ≥ 240 dyn*sec/cm5 or ≥ 3 WU obtained on most recent RHC obtained prior to screening; [Sub-population B only - without a remote PAP sensor]; Hemodynamic evidence of Cpc-PH based on the presence of all the following RHC parameters obtained during the Screening period, prior to randomization:; PVR ≥ 240 dyn*sec/cm5 or ≥ 3 WU, and; mPAP > 20 mmHg, and; PAWP > 15 mmHg but < 30 mmHg, and; dPAP ≥ 15 mmHg; Established diagnosis of HFpEF with left ventricular ejection fraction (LVEF) ≥ 45 % as measured by echocardiography during Screening and and no documented LVEF < 45% during the 2 years preceding Screening; New York Heart Association (NYHA) class II or III heart failure symptoms; Stable diuretic regimen during the screening period; Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) < 90 at screening; 6-minute walking distance (6MWD) ≥ 100 m at screening; Body mass index ≥ 25 to ≤ 50 kg/m2 and Body weight ≤140 kg; Ability to adhere to study visit schedule and understand and comply with all protocol requirements.

Exclusion: Hospitalization for any worsening medical condition or major surgery within 4 weeks prior to screening; Occurrence of an acute coronary syndrome, percutaneous coronary intervention, or cardiac surgery within 90 days prior to Screening; Implantation of a cardiac resynchronization therapy (CRT) device within 90 days before screening; History of serious or life-threatening cardiac arrhythmia within 90 days prior to screening; History of heart transplant or on heart transplant list; Systemic hypotension or uncontrolled systemic hypertension; History of Pericardial constriction or hypertrophic cardiomyopathy; History of significant valvular stenosis or regurgitation; Participants with a pneumonectomy or more than moderate Chronic Obstructive Pulmonary Disease (COPD) or mild interstitial lung disease (ILD) or untreated mild obstructive sleep apnea (OSA); Planned cardiovascular revascularization or planned implantation of CRT device.

ClinicalTrials.gov NCT07123779