Phase 2b Open-Label Study Evaluating Tolerability and Safety of 5 mg Vericiguat in Chronic Heart Failure with Reduced Ejection Fraction
- Trial ID
- 2023-507682-25-00
- Protocol
- 21683 "VELOCITY"
- Sponsor
- Bayer AG
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 2b open-label clinical study is to evaluate the **tolerability** of a 5 mg starting dose of **vericiguat** in participants with **chronic heart failure with reduced ejection fraction**. This is clinically relevant as determining the tolerability of vericiguat at this dosage could inform treatment protocols and improve patient outcomes by optimizing the initiation dose for this patient population.
Secondary objectives include:
- Describing safety events associated with the initiation of the 5 mg dose.
- Further evaluating the tolerability of 5 mg as a starting dose of vericiguat.
Participants
The clinical trial involved a total of **27 participants** diagnosed with **chronic heart failure with reduced ejection fraction**. The study population included both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific inclusion criteria, such as having a left ventricular ejection fraction (LVEF) of less than 45% assessed within 12 months prior to the initial visit, and maintaining a systolic blood pressure of at least 100 mmHg at screening and the first visit. The trial did not include a vulnerable population. Participants were required to have stable doses of guideline-directed medical therapy (GDMT) for heart failure, with no changes in medication dosing within a specified period before screening. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria. The trial aimed to evaluate the tolerability of a 5 mg starting dose of vericiguat in this population.
Plans and Procedures
The clinical trial is designed as a **Phase 2b open-label 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**. The trial aims to assess the tolerability of vericiguat as a starting dose, with the primary endpoint being the completion of the two-week 5 mg dose without discontinuation or moderate to severe symptomatic hypotension. Secondary endpoints include the reporting of any adverse events (AEs) and the continuous intake of the study intervention between visits.
The trial is expected to commence recruitment on May 21, 2024, and conclude by January 7, 2025. Participants will be involved in the study for a maximum treatment period of 18 weeks. The study includes several key visits: an inclusion (screening) visit, where eligibility is confirmed based on criteria such as left ventricular ejection fraction (LVEF) of less than 45% and stable guideline-directed medical therapy (GDMT) dosing. Follow-up visits will monitor the participants' response to the treatment, with a focus on tolerability and safety. The end-of-study visit will assess the overall outcomes and any long-term effects of the treatment.
Participants may be terminated early from the study if they experience significant adverse events, fail to adhere to the study protocol, or if there are any changes in their medical condition that contraindicate continued participation. The study is not a low-intervention trial and does not involve a pediatric formulation. The pharmaceutical form of the investigational product is a film-coated tablet, administered orally. The trial is sponsored by Bayer Healthcare AG, and the investigational product is identified by the code BAY 1021189.
Treatment
The clinical trial involves the administration of **vericiguat**, an experimental medication, to evaluate its tolerability and safety in participants with chronic heart failure with reduced ejection fraction. The investigational product, identified as BAY 1021189, is provided in the form of a **film-coated tablet**. The active substance, vericiguat, is of chemical origin and is manufactured by Bayer Healthcare AG. The trial protocol specifies an initiation dose of 5 mg, administered orally once daily. The maximum daily dose is set at 5 mg, with a total maximum dose of 90 mg over the course of the study. The treatment period is limited to a maximum of 18 weeks.
In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of vericiguat to assess its effects. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is designed to provide comprehensive data on the tolerability of vericiguat as a starting dose in the specified patient population.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the evaluation of treatment tolerability. The primary endpoints include the completion of a two-week 5 mg dose of **vericiguat** without discontinuation of the study intervention and without moderate to severe symptomatic hypotension between Visit 1 and Visit 2. Secondary endpoints will focus on the occurrence of any adverse events (AEs) reported between Visit 1 and Visit 2, the absence of AEs related to the study intervention during this period, and the continuous intake of the study intervention or the restart of the intervention after any temporary interruption.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- SBP ≥ 100 mmHg at screening and Visit 1 (pre-treatment)
- No changes in GDMT dosing (including beta blockers, ACEI/ARBs, ARNI, MRAs, hydralazine-nitrate combinations, SGLT2 inhibitors, ivabradine, or oral diuretics) • Within 4 weeks of screening for participants without a 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 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, NSTEMI, or STEMI), undergone CABG or PCI within 3months before Visit 1, or indication for coronary revascularization at the time of treatment assignment.
- Symptomatic carotid stenosis, TIA, or stroke within 3months 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 of hypovolemia within 4 weeks of screening and during screening period.
- Currently hospitalized.
- eGFR based on the CKD-EPI Creatinine Equation of <15mL/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 ALBI Grade 3 or hepatic encephalopathy, or has hepatic laboratory abnormalities (ALT or AST ≥3 × 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 sGC stimulator.
- Amyloidosis or sarcoidosis.
- Concurrent or anticipated concomitant use of 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Hungary | Not Recruiting | 21 May 2024 | 16 |
 Italy | Not Recruiting | 21 May 2024 | 16 |
 Poland | Not Recruiting | 21 May 2024 | 56 |
 Spain | Not Recruiting | 21 May 2024 | 15 |
 Sweden | Not Recruiting | 21 May 2024 | 8 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
BAY 1021189 | Test | FILM-COATED TABLET | ORAL | 5 | 18 | PRD2732384 |