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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bayer AG, Bayer AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

13 May 2024 → 30 Jul 2024

Decision date (initial)

2024-05-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bayer AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

To evaluate the tolerability of 5 mg as a starting dose of vericiguat

Secondary objectives 2

1. To describe safety events of initiation of 5 mg dose
2. To further evaluate the tolerability of 5 mg as a starting dose of vericiguat

Conditions and MedDRA coding

Chronic heart failure with reduced ejection fraction

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Food And Drug Administration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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.
2. SBP ≥ 100 mmHg at screening and Visit 1 (pre-treatment)
3. 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
4. No expected medical procedures to occur 2 weeks before screening or during study participation.
5. 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 22

1. History of symptomatic hypotension 4 weeks before screening.
2. Primary valvular heart disease requiring surgical procedure or intervention or has undergone a vascular surgical procedure or intervention within 3months before Visit 1
3. Hypertrophic cardiomyopathy
4. Acute myocarditis or Takotsubo cardiomyopathy
5. 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.
6. Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia.
7. 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.
8. Symptomatic carotid stenosis, TIA, or stroke within 3months before Visit 1.
9. 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.
10. Active endocarditis or constrictive pericarditis.
11. Hemodynamic instability of hypovolemia within 4 weeks of screening and during screening period.
12. Currently hospitalized.
13. 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
14. 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.
15. Malignancy or other noncardiac condition limiting life expectancy to <3years.
16. Requires continuous home oxygen for severe pulmonary disease.
17. Interstitial lung disease.
18. Known allergy or hypersensitivity to vericiguat, any of its constituents, or any other sGC stimulator.
19. Amyloidosis or sarcoidosis.
20. Concurrent or anticipated concomitant use of PDE5 inhibitors such as vardenafil, tadalafil, and sildenafil during the study.
21. Concurrent use of an sGC stimulator such as riociguat or vericiguat.
22. Prior (within 2 weeks prior to screening) or anticipated concomitant administration of IV / SC diuretics or inotropes.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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

Secondary endpoints 3

1. Any AE reported between Visit 1 and 2
2. Absence of AE related to study intervention between Visit 1 and Visit 2.
3. Continuous intake of study intervention between Visit 1 and Visit 2 or restart of study intervention after any temporary interruption.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bayer AG

Sponsor organisation

Bayer AG

Address

Kaiser-Wilhelm-Allee 1, Wiesdorf Wiesdorf

City

Leverkusen

Postcode

51373

Country

Germany

Scientific contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Public contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Third parties 2

Bayer AG

Sponsor organisation

Bayer AG

Address

-

City

Leverkusen

Postcode

51368

Country

Germany

Locations

5 EU/EEA countries · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications