A Study to Learn How Safe Starting Vericiguat at a Dose of 5 Milligrams is in Participants With Chronic Heart Failure With Reduced Ejection Fraction

A Phase 2b Open-label Clinical Study to Evaluate the Tolerability and Safety of an Initiation Dose of 5 mg of Vericiguat in Participants With Chronic Heart Failure With Reduced Ejection Fraction

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06195930

Enrollment

106

Registered

2024-01-08

Start date

2024-04-18

Completion date

2024-07-29

Last updated

2025-09-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Heart Failure With Reduced Ejection Fraction

Keywords

HFrEF

Brief summary

Researchers are looking for a better way to treat people who have chronic heart failure with reduced ejection fraction. Chronic heart failure with reduced ejection fraction (HFrEF) is a long-term condition that occurs when the heart is too weak to pump enough blood to the rest of the body. This results in a reduced supply of the oxygen that the body requires to function properly. The common symptoms of HFrEF include breathlessness, weakness, fatigue, and swelling in the ankles and legs. If left untreated, heart failure can lead to other serious health problems, including damage to other organs, which may result in hospital stays or even death. Vericiguat is an approved drug for use in people with chronic HFrEF. It works by activating a protein called soluble guanylate cyclase, which helps dilating the blood vessels and in turn improves heart function. Currently, treatment with vericiguat starts at a daily dose of 2.5 milligrams (mg), which increases to 5 mg after 2 weeks. The dose is then increased to the target dose of 10 mg after another 2 weeks. In this study, researchers are trying to learn how well participants can tolerate and how safe it is to start vericiguat at a dose of 5 mg. Starting directly at the 5 mg dose is expected to help reach the target dose of 10 mg faster. Participants will take vericiguat 5 mg as a tablet by mouth once daily along with their regular heart medications. At the start of the study, study doctors will check participants' medical history and perform full health check-ups to confirm if they can take part in the study. Throughout the study, study doctors will monitor participants' previous and current medications, their heart health, and their overall well-being. This will help researchers assess how safe the study drug is and if they experience adverse events. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective of whether they think they are related to the study treatment. Access to study treatment after the end of this study is not planned. Everyone, including study doctors and participants, will know what drug the participants receive during the study. Participants may be in the study for about 4 weeks. Participants may not benefit from the treatment as the study is designed to assess safety and tolerability: the duration of the study is very short and participants will be taking a low dose of vericiguat without moving to the target dose of 10 mg during the study. However, the findings of this study may enable people with chronic HFrEF to safely skip one initial dosing step and reach the target dose of vericiguat faster. Participants may experience medical problems such as low blood pressure, upset stomach, nausea, dizziness, and headache. Researchers will monitor and manage all these, and other, medical problems participants may have during the study.

Interventions

DRUGVericiguat (BAY1021189) 5 mg

Vericiguat (BAY1021189) will be taken as 5 mg tablet 1x daily over at least 14 days up to 18 days (+ 4 days time window allowed)

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

This is a multi-center, single arm, open label study of vericiguat initiation at 5 mg in HFrEF patients with EF \<45%. The total study duration is approximately 4 weeks, including a 2-week screening period and a 2-week treatment period . Screening: Approximately 120 participants will be screened to achieve at least 100 participants who are assigned to study intervention and complete the treatment period of up to 2 weeks. Participants will undergo a screening visit to assess eligibility. Eligible participants must wait a mandatory 2 weeks before returning for Visit 1 in order to be clinically and hemodynamically stable. Treatment: At Visit 1, participants will receive vericiguat 5 mg (on top of standard of care) with directions to take once daily for 2 weeks. Participants will return for a study visit (Visit 2) after 2 weeks of treatment. Unscheduled visits may be utilized between Visits 1 and 2 at the discretion of the investigator for AE review and reporting.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Has an Left ventricle ejection fraction (LVEF) of \<45% assessed within 12 months before Visit 1 by local any imaging method, and no subsequent LVEF measurement \> 45%. The most recent measurement must be used to determine eligibility. * systolic blood pressure (SBP) ≥ 100 mmHg at screening and Visit 1 (pre-treatment). * No changes in guideline-directed medical therapy for heart failure (GDMT) dosing (including beta blockers, angiotensin-converting enzyme inhibitor/ angiotensin II receptor blocker (ACEI/ARBs), angiotensin receptor-neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonist (MRAs), hydralazine-nitrate combinations, sodium-glucose cotransporter 2 i(SGLT2) inhibitors, ivabradine, or oral diuretics): * Within 4 weeks of screening for participants without a heart failure (HF) event ≤6 months prior to screening * within 2 weeks of screening for participants with a HF event ≤6 months prior to screening * planned during study participation * No expected medical procedures to occur 2 weeks before screening or during study participation. * Participants with ( group 1) OR without (group 2) recent worsening HF event Group 1: History of chronic HF (NYHA class II symptomatic-IV) on GDMT with recent HFevent within 6 months of screening or outpatient IV / SC diuretic use within 3 months before screening. OR Group 2: History of chronic HF (NYHA class II symptomatic-IV) on GDMT without recent HF event within 6 months of screening or outpatient intravenous/ subcutaneous (IV / SC) diuretic use within 3 months before screening.

Exclusion criteria

* History of symptomatic hypotension 4 weeks before screening * Primary valvular heart disease requiring surgical procedure or intervention or has undergone a vascular surgical procedure or intervention within 3months before visit 1 * Hypertrophic cardiomyopathy * Acute myocarditis or Takotsubo cardiomyopathy * Awaiting heart transplantation (United Network for Organ Sharing Class 1A /1B or equivalent) or has or anticipates receiving an implanted ventricular assist device, or has received a heart transplant. * Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia. * Acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction (NSTEMI), or ST elevation myocardial infarction (STEMI), undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) within 3months before Visit 1, or indication for coronary revascularization at the time of treatment assignment. * Symptomatic carotid stenosis, transient ischemic attack (TIA), or stroke within 3 months before Visit 1. * History of repaired or unrepaired simple congenital heart disease (e.g., atrial or ventricular septal defects, or patent ductus arteriosus) with ongoing hemodynamically significant residual lesions, or any history of complex congenital heart disease (e.g. tetralogy of Fallot, transposition of the great arteries, single ventricle disease) regardless of repair status. * Active endocarditis or constrictive pericarditis. * Hemodynamic instability or hypovolemia within 4 weeks of screening and during the screening period. * Currently hospitalized. * estimated glomerular filtration rate (eGFR) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation of \<15 mL/min/1.73 m2 within 30 days before Visit 1 or on chronic dialysis. For participants with multiple eGFR results during screening, the most recent value will be used to determine eligibility. * Severe hepatic insufficiency defined as albumin to bilirubin ratio (ALBI) Grade 3 or hepatic encephalopathy, or has hepatic laboratory abnormalities (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 ×upper limit of normal (ULN) or total bilirubin ≥2 × ULN). Exceptions for Gilbert's syndrome will be considered. Albumin, ALT, AST, and total bilirubin results within 30 days before Visit 1 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. * Malignancy or other noncardiac condition limiting life expectancy to \<3years. * Requires continuous home oxygen for severe pulmonary disease. * Interstitial lung disease. * Known allergy or hypersensitivity to vericiguat, any of its constituents, or any other soluble guanylate cyclase (sGC) stimulator. * Amyloidosis or sarcoidosis. * Concurrent or anticipated concomitant use of phosphodiesterase type 5 (PDE5) inhibitors such as vardenafil, tadalafil, and sildenafil during the study. * Concurrent use of an sGC stimulator such as riociguat or vericiguat. * Prior (within 2 weeks prior to screening) or anticipated concomitant administration of IV / SC diuretics or inotropes.

Design outcomes

Primary

Measure	Time frame	Description
Treatment Tolerability: Number of Participants Without Discontinuation of Study Intervention (Incl. Max. 1 Day Interruption) and Without Moderate to Severe Symptomatic Hypotension	Between Visit 1 (Day 1) and Visit 2 (Day 14 up to Day 18 if +4 days time window is used)	Treatment tolerability, defined as the completion of the two-week 5 mg dose without discontinuation of study intervention (incl. max. 1 day interruption) and without moderate to severe symptomatic hypotension between Visit 1 and Visit 2
Treatment Tolerability: Number of Participants Without Discontinuation of Study Intervention (Max. 2 Day Interruption Included) and Without Moderate to Severe Symptomatic Hypotension	Between Visit 1 (Day 1) and Visit 2 (Day 14 up to Day 18 if +4 days time window is used)	Treatment tolerability, defined as the completion of the two-week 5 mg dose without discontinuation of study intervention (incl. max. 2 day interruption) and without moderate to severe symptomatic hypotension between Visit 1 and Visit 2

Secondary

Measure	Time frame	Description
Number of Participants With Any Adverse Event (AE) Reported Between Visit 1 and Visit 2	Between Visit 1 (Day 1) and Visit 2 (Day 14 up to Day 18 if +4 days time window is used)	Any AE reported between Visit 1 and Visit 2 to describe the safety events of initiation of 5mg dose.
Number of Participants With no AE Related to Study Intervention Between Visit 1 and Visit 2	Between Visit 1 (Day 1) and Visit 2 (Day 14 up to Day 18 if +4 days time window is used)	Absence of AEs related to study intervention between Visit 1 and Visit 2 to describe safety events of initiation of 5mg dose.
Number of Participants With Continuous Intake of Study Intervention Between Visit 1 and Visit 2 or Restart of Study Intervention After Any Temporary Interruption.	Between Visit 1 (Day 1) and Visit 2 (Day 14 up to Day 18 if +4 days time window is used)	To further evaluate the tolerability of 5mg as a starting dose

Countries

Argentina, Hungary, Italy, Poland, Spain, Sweden, United States

Participant flow

Participants by arm

Arm	Count
Vericiguat 5 mg Participants who started with study intervention intake: Vericiguat 5 mg - At Visit 1, subjects received vericiguat (BAY1021189) 5 mg oral as tablet (on top of standard of care) with directions to take once daily for 14 days (up to 18 days: +4 day time window allowed).	106
Total	106

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	4

Baseline characteristics

Characteristic	Vericiguat 5 mg
Age, Continuous	66.9 Years STANDARD_DEVIATION 11.3
Age, Customized 85 years and over	3 Participants
Age, Customized between 18 and 64 years	42 Participants
Age, Customized from 65 to 84 years	61 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	39 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
History of HF event Participants without recent worsening HF event (Group 2)	53 Participants
History of HF event Participants with recent worsening HF event (Group 1)	53 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	102 Participants
Sex: Female, Male Female	30 Participants
Sex: Female, Male Male	76 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 106
other Total, other adverse events	14 / 106
serious Total, serious adverse events	1 / 106

Outcome results

Primary

Treatment Tolerability: Number of Participants Without Discontinuation of Study Intervention (Incl. Max. 1 Day Interruption) and Without Moderate to Severe Symptomatic Hypotension

Treatment tolerability, defined as the completion of the two-week 5 mg dose without discontinuation of study intervention (incl. max. 1 day interruption) and without moderate to severe symptomatic hypotension between Visit 1 and Visit 2