A Study of Vericiguat (MK-1242) in Participants With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

29 Oct 2021 → 6 Feb 2025

Decision date (initial)

2023-05-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC · Bayer AG

External identifiers

EU CT number

2022-500881-80-00

EudraCT number

2020-005941-18

WHO UTN

U1111-1278-5066

ClinicalTrials.gov

NCT05093933

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Pharmacokinetic, Others

To evaluate the efficacy of vericiguat compared with placebo on reducing the risk of cardiovascular death or heart failure hospitalization.

Secondary objectives 5

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.

Conditions and MedDRA coding

Chronic Heart Failure With Reduced Ejection Fraction

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. History of chronic HF [New York Heart Association (NYHA) Class II to IV] on guideline-directed medical therapy for heart failure (GDMT) with no HF hospitalization within 6 months or outpatient IV diuretic use within 3 months before randomization.
2. Left ventricular ejection fraction (LVEF) of ≤40%, assessed within 12 months before randomization by any imaging method.
3. Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.
4. A female participant is eligible to participate if she is not pregnant or breastfeeding, is not a woman of childbearing potential (WOCBP), or is a WOCBP and agrees to follow contraceptive guidance during the study intervention period and for at least 1 month after the last dose of study intervention.

Exclusion criteria 15

1. Has SBP <100 mm Hg or symptomatic hypotension.
2. Awaiting heart transplantation, is receiving continuous IV infusion of an inotrope, or has or anticipates receiving an implanted ventricular assist device.
3. Amyloidosis or sarcoidosis.
4. Primary valvular heart disease requiring surgical procedure or intervention or has undergone a valvular surgical procedure or intervention within 3 months before randomization.
5. Hypertrophic cardiomyopathy.
6. Acute myocarditis or Takotsubo cardiomyopathy.
7. History of heart transplant.
8. Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia.
9. Acute coronary syndrome, or undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) within 3 months before randomization.
10. History of symptomatic carotid stenosis, transient ischemic attack (TIA), or stroke within 3 months before randomization.
11. Malignancy or other noncardiac condition limiting life expectancy to <3 years.
12. Requires continuous home oxygen for severe pulmonary disease.
13. Interstitial lung disease.
14. Discontinuation or dose modification of GDMT or vericiguat within 4 weeks before randomization.
15. Recent history (within the last year) of drug or alcohol abuse or dependence.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization

Secondary endpoints 8

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)

Investigational products

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

Test 3

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Ciaran Joseph McMullan

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Ciaran Joseph McMullan

Third parties 9

Locations

12 EU/EEA countries · 138 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 41 files

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

Application history

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