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

Phase 1

Recruiting

• Conditions: Heart Failure; MedDRA version: 20.0Level: LLTClassification code: 10019279Term: Heart failure Class: 10007541; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: CTIS2023-504678-39-00
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-10-31
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 740

Inclusion Criteria

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.

Exclusion Criteria

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., Office systolic blood pressure (SBP) = 180 mmHg or < 105 mmHg at screening or at randomization., In subjects with ACEI/ARB medication at screening, previous inability to tolerate any dose of sacubitril/valsartan (as per the investigator's judgment)., 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., Known history of angioedema.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy and dose-response relationship of three XXB750 target dose levels compared to placebo in reducing N-terminal prohormone B-type natriuretic peptide (NT-proBNP) from baseline to Week 16 in symptomatic HF patients with LVEF < 50% treated with standard of care, including ACEI/ARB or sacubitril/valsartan.;Secondary Objective: To evaluate the treatment effect of the highest XXB750 target dose level compared to placebo in reducing NT-proBNP from baseline to Week 16 in symptomatic HF patients with LVEF <50% treated with standard of care, including ACEI/ARB or sacubitril/valsartan., To evaluate the treatment effect of combined two highest XXB750 target dose levels administered in addition to a background of ACEI/ARB versus conversion from ACEI/ARB to sacubitril/valsartan, in reducing NT-proBNP from baseline to Week 16., To evaluate the safety and tolerability of XXB750 up-titration regimens and dose levels.;Primary end point(s): Change in log NT-proBNP from baseline to Week 16

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Change in log NT-proBNP from baseline to Week 16;Secondary end point(s):Adverse events, safety laboratory parameters, and vital signs from baseline to end of study (EOS)