A proof of concept and dose-finding study of XXB750 in patients with heart failure

Prior treatment

• Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy) or hospitalization for HF within 3 months prior to screening.
• In subjects with ACEI/ARB medication at screening, previous inability to tolerate any dose of sacubitril/valsartan (as per the investigator's judgment).

Other illness

• Known history of angioedema.

Lab values

• Serum potassium > 5.4 mmol/L at screening.
• Estimated GFR (eGFR) < 30 mL/min/1.73m2 at screening as measured by the CKD-EPI formula.

Other

• Office systolic blood pressure (SBP) ≥ 180 mmHg or < 105 mmHg at screening or at randomization.

• Written informed consent must be obtained before any assessment is performed.
• Male and female outpatients who are ≥ 18 years old.
• Symptom(s) of HF NYHA class II-III at Screening.
• LVEF < 50% (most recent local measurement, made within 6 months prior to or during screening using echocardiography, MUGA, CT scanning, MRI or ventricular angiography is acceptable, provided no subsequent measurement ≥ 50%).
• NT-proBNP ≥ 600 pg/ml if in sinus rhythm or  NT-proBNP ≥ 900 pg/ml if in atrial fibrillation/flutter at Screening.
• Receiving an ACEI or an ARB at a stable dose of at least enalapril 10 mg/d or equivalent for at least 4 weeks before Screening or receiving sacubitril/valsartan at a stable dose of at least 49/51 mg bid for at least 4 weeks before Screening.
• Receiving other guideline recommended HF therapies as deemed appropriate by the investigator and that are stable for at least 4 weeks before Screening, unless contraindicated, not tolerated, or not available to patient.