Safety & Effectiveness of Tovinontrine in Chronic Heart Failure With Preserved Ejection Fraction (Cycle-2-PEF)

Prior treatment

• Has had a prior or planned orthotopic heart transplantation;

Other illness

• Has elective interventions (eg, percutaneous coronary intervention, device implantations, percutaneous structural heart disease interventions, cardiac and non-cardiac surgery) planned to occur during involvement in this study;
• Has acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery, or carotid angioplasty within 60 days of the time of Screening or during the Screening Period;

Other

• Has documented EF ≥ 60% by TTE within 6 months of the time of Screening or during the Screening Period;
• Has evidence of recent HF exacerbation defined by hospitalization or requirement for IV or SQ diuretics within 60 days of the time of Screening or during the Screening Period;
• Has a requirement for routine, scheduled outpatient IV infusions for HF (ie, inotropes, vasodilators, or diuretics) or routinely scheduled ultrafiltration;
• Has presence of or plan for mechanical circulatory support;
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

• Is an adult male or female patient ≥ 18 years of age
• Has evidence in the medical history supporting a diagnosis of clinical HF syndrome, NYHA functional class II to III, with the duration of at least 6 months prior to the time of Screening. The HF syndrome is defined by documentation of 1 or more of the following:
  • At least 1 of the typical symptoms due to HF such as dyspnea and/or fatigue limiting exercise capacity;
  • At least 1 of the typical signs of HF such as peripheral edema, elevated jugular venous pressure, pulmonary crackles; or
  • Hospitalization, emergency department visit, or outpatient visit for HF requiring intravenous (IV) or subcutaneous (SQ) diuresis within the past 12 months.
• Has ejection fraction (EF) \>40% and left atrial enlargement by transthoracic echocardiogram (TTE) performed and interpreted locally at the time of Screening;
• Has NT-proBNP level ≥ 300 pg/mL at the time of Screening. Patients with atrial fibrillation or flutter at the time of Screening are required to have an NT proBNP level of ≥500 pg/mL at the time of Screening;
• Is on stable optimized doses of guideline-directed HF therapy, per Investigator's clinical judgment, for a minimum of 4 weeks prior to the time of Screening and during the Screening Period, with no planned changes after randomization; Has had no addition of new guideline-directed HF therapy within the 3 months prior to the time of Screening or during the Screening Period;