Chronic Heart Failure with reduced Ejection Fraction MedDRA version: 20.0 Level: LLT Classification code 10078289 Term: Heart failure with reduced ejection fraction System Organ Class: 100000004849
Conditions
Interventions
Product Name: Vericiguat
Product Code: MK-1242
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Vericiguat
CAS Number: 1350653-20-1
Current Sponsor code: MK-1242
Other descriptive name: BAY 102
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has a history of chronic HF (NYHA Class II to IV) on GDMT with no events of HFH within 6 months or outpatient IV diuretic use within 3 months before randomization. 2. Is male or female, at least 18 years of age, at the time of providing documented informed consent. 3. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a WOCBP OR • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 3500
Exclusion criteria
Exclusion criteria: 1. Has SBP <100 mm Hg or symptomatic hypotension. 2. Has a known allergy or sensitivity to vericiguat, any of its constituents, or any other sGC stimulator. 3. Is awaiting heart transplantation (United Network for Organ Sharing Class 1A / 1B or equivalent), is receiving continuous IV infusion of an inotrope, or has or anticipates receiving an implanted ventricular assist device. 4. Has amyloidosis or sarcoidosis. 5. Has primary valvular heart disease requiring surgical procedure or intervention or has undergone a valvular surgical procedure or intervention within 3 months before randomization. 6. Has hypertrophic cardiomyopathy. 7. Has acute myocarditis or Takotsubo cardiomyopathy. 8. Has received a heart transplant. 9. Has tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia. 10. Has acute coronary syndrome (unstable angina, NSTEMI, or STEMI), undergone CABG or PCI within 3 months before randomization, or indication for coronary revascularization at the time of randomization. 11. Has symptomatic carotid stenosis, TIA, or stroke within 3 months before randomization. 12. Has a history of repaired or unrepaired simple congenital heart disease (eg, atrial or ventricular septal defects, or patent ductus arteriosus) with ongoing hemodynamically significant residual lesions, or any history of complex congenital heart disease (eg, tetralogy of Fallot, transposition of the great arteries, single ventricle disease) regardless of repair status. 13. Has active endocarditis or constrictive pericarditis. 14. Has an eGFR based on the CKD-EPI Creatinine Equation of <15 mL/min/1.73 m2 within 30 days before randomization or is on chronic dialysis. For participants with multiple eGFR results during screening, the most recent value will be used to determine eligibility at the Randomization Visit. 15. Has severe hepatic insufficiency defined as ALBI Grade 3 or hepatic encephalopathy, or has hepatic laboratory abnormalities (ALT or AST =3 × ULN or total bilirubin =2 × ULN). Screening albumin, ALT, AST, and total bilirubin results within 30 days before randomization may be used for assessment of laboratory abnormalities or the calculation of the ALBI score. For participants with multiple albumin and/or total bilirubin results during screening, the most recent value for each test will be used to calculate ALBI score. 16. Has malignancy or other noncardiac condition limiting life expectancy to <3 years. 17. Requires continuous home oxygen for severe pulmonary disease. 18. Has interstitial lung disease. 19. Had any discontinuation or dose modification of GDMT (including beta blockers, ACEI/ARBs, ARNI, MRAs, hydralazine-nitrate combinations, SGLT2is, or ivabradine) or vericiguat within 4 weeks before randomization. 20. Has concurrent or anticipated concomitant use of PDE5 inhibitors such as vardenafil, tadalafil, and sildenafil during the study. 21. Has concurrent use of an sGC stimulator such as riociguat or vericiguat. 22. Has participated in another interventional clinical study or has been treated with another investigational product =30 days before randomization or plans to participate in any other study or study intervention during this study. 23. Has a recent history (within the last year) of drug or alcohol abuse or dependence. 24. Is pregnant or breastfeeding or plans to become pregnant or to breastfeed during the study. 25. Has a medical disorder, condition, or history thereof that in the opinion of the investigator would impair the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the efficacy of vericiguat compared with placebo on reducing the risk of cardiovascular death or heart failure hospitalization.;Secondary Objective: 1. To evaluate the efficacy of vericiguat compared with placebo on reducing the risk of cardiovascular death. 2. To evaluate the efficacy of vericiguat compared with placebo in reducing the risk of heart failure hospitalization. 3. To evaluate the efficacy of vericiguat compared with placebo in reducing the risk of all-cause mortality or heart failure hospitalization. 4. To evaluate the efficacy of vericiguat compared with placebo in reducing the risk of all-cause mortality. 5. To evaluate the safety and tolerability of vericiguat compared with placebo. ;Primary end point(s): 1. Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization;Timepoint(s) of evaluation of this end point: 1. From date of randomization until the date of first occurrence of a primary end point, assessed up to approximately 40 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to First Occurrence of CV Death 2. Time to First Occurrence of HF Hospitalization 3. Time to Total HF Hospitalizations (Including First and Recurrent Events) 4. Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization 5. Time to All-Cause Mortality 6. Percentage of Participants who Experienced One or More Selected Nonserious Adverse Events (NSAE) 7. Percentage of Participants Who Experienced One or More Serious Adverse Events (SAE) 8. Percentage of Participants Who Experienced One or More Events of Clinical Interest (ECI) ;Timepoint(s) of evaluation of this end point: 1. From date of randomization until the date of first occurrence of a CV Death, assessed up to approximately 40 months 2. From date of randomization until the date of first occurrence of a HF Hospitalization, assessed up to approximately 40 months 3. Up to approximately 40 months 4. From date of randomization until the date of first occurrence of All-Cause Mortality or HF Hospitalization, assessed up to approximately 40 months 5. From date of randomization until the date of death, assessed up to approximately 40 months 6. Up to approximately 40 months 7. Up to approximately 40 months 8. Up to approximately 40 months | — |
Countries
Argentina, Australia, Austria, Brazil, Canada, Chile, China, Colombia, Czechia, Czech Republic, Denmark, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Ireland, Israel, Italy, Korea, Republic of, Malaysia, Mexico, New Zealand, Peru, Poland, Puerto Rico, Russian Federation, Singapore, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Outcome results
None listed