A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction (HFrEF) (MK-1242-001) (VICTORIA)

SECONDARY IDENTIFICATION NUMBER

MK-1242-001-04, VICTORIA; CT.gov: NCT02861534

FDA CLINICAL TRIAL REFERENCE (CTR) NUMBER

2016-CT0367

SCIENTIFIC TITLE

A Randomized Parallel-Group, Placebo-Controlled, Double-Blind, Event-Driven, Multi-Center Pivotal Phase III Clinical Outcome Trial of Efficacy and Safety of the Oral sGC Stimulator Vericiguat in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF) - VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA)

PROJECT DESCRIPTION

This is a randomized, placebo-controlled, parallel-group, multi-center, double-blind, event driven study of vericiguat (MK-1242) in participants with HFrEF. The primary hypothesis is vericiguat (MK-1242) is superior to placebo in increasing the time to first occurrence of the composite of cardiovascular (CV) death or heart failure (HF) hospitalization in participants with HFrEF.

NUHRA DETAILS

Regime Classification Priority 2010 - 2016 Health Technology Development Drug Discovery and Development

PROJECT DURATION

Start Date Duration in Months Target Completion Date Actual Completion Date 2017-01-30 36 2020-01-30 2020-03-04

PROJECT STATUS

Completed

REASON FOR PROJECT PENDING/SUSPENSION/TERMINATION

Unspecified

IMPLEMENTING AGENCY (PRIMARY SPONSOR)

Institution Classification Region LTO # Merck Sharp & Dohme (I.A.) LLC Private Business NCR CDRR-NCR-S-16

COOPERATING AGENCY (SECONDARY SPONSOR)

Institution Classification Region LTO # No records Found.

CONTRACT RESEARCH ORGANIZATION (CRO) INFORMATION

Contact #s.: (+632) 8377534, (+632) 8377537, (+632) 8372071-80 loc. 2117, 2112 Saliksik Building, DOST Compound, Gen. Santos Ave., Bicutan Taguig City 1631 Philippines Page 1/6 Institution Classification Region LTO # No records Found.

FUNDING AGENCY (SOURCES OF MONETARY OR MATERIAL SUPPORT)

Institution Amount Region Merck Sharp & Dohme (I.A.) LLC P 3,496,600,150.00 NCR

CONTACT FOR PUBLIC QUERIES

Name E-Mail Phone Number Institution and Institution Address Priscila D. Perez [email protected] +639178118093 26/F Philamlife Tower , 8767 Paseo de Roxas, Makati City, 1226 Philippines

CONTACT FOR SCIENTIFIC QUERIES

Name E-Mail Phone Number Institution and Institution Address Priscila D. Perez [email protected] +639178118093 26/F Philamlife Tower , 8767 Paseo de Roxas, Makati City, 1226 Philippines

IMPLEMENTING AGENCY (PRIMARY SPONSOR)

Name Expertise Affiliation Amelita Brillantes, MD Medical Doctor University of Perpetual Help (Dr. Jose G. Tamayo Medical University) David Raymund Salvador, MD Medical Doctor De La Salle Health Sciences Institute Eugenio B. Reyes, MD Medical Doctor Manila Doctors Hospital Gabriel B. Jocson III, MD Medical Doctor Angeles University Foundation Medical Center Louie S. Tirador, MD Medical Doctor St. Paul's Hospital of Iloilo, Inc. Ramoncito S. Habaluyas, MD Medical Doctor Philippine Heart Center Rody G. Sy Medical Doctor Cardinal Santos Medical Center

RESEARCH CLASSIFICATION

Clinical Trial

HEALTH CONDITION(S) OR PROBLEM(S) STUDIED

Heart FailureChronic Heart Failure With Reduced Ejection Fraction

PRIMARY OUTCOMES

Primary Outcome Measures: - Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure Hospitalization [ Time Frame: Up to approximately 3.5 years ]

KEY SECONDARY OUTCOMES

Secondary Outcome Measures: - Time to the First Occurrence of CV Death [ Time Frame: Up to approximately 3.5 years ] - Time to the First Occurrence of HF Hospitalization [ Time Frame: Up to approximately 3.5 years ] - Time to Total HF Hospitalizations (including frst and recurrent events) [ Time Frame: Up to approximately 3.5 years ] - Time to First Occurrence of Composite Endpoint of All-cause Mortality or HF Hospitalization [ Time Frame: Up to approximately 3.5 years ] - Time to All-cause Mortality [ Time Frame: Up to approximately 3.5 years ]

RECRUITMENT STATUS

Contact #s.: (+632) 8377534, (+632) 8377537, (+632) 8372071-80 loc. 2117, 2112 Saliksik Building, DOST Compound, Gen. Santos Ave., Bicutan Taguig City 1631 Philippines Page 2/6 Completed

COUNTRIES OF RECRUITMENT

Argentina, Australia, Austria, Belgium, Canada, Chile, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Puerto Rico, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States

FDA DOCUMENT TRACKING NUMBER

20160810154722

FDA APPROVAL DATE

2016-10-20

ERC APPROVAL DATE

0000-00-00

FIRST ENROLMENT DATE

2017-01-30

TARGET SAMPLE SIZE (PHILIPPINES)

60

ACTUAL SAMPLE SIZE (PHILIPPINES)

62

REASON FOR THE DIFFERENCE BETWEEN TARGET & ACTUAL SAMPLE SIZES

Unspecified

DATE OF FIRST ENROLMENT

2017-01-30

KEY INCLUSION AND EXLUSION CRITERIA (CT)

Protocol 1242-001-04 Inclusion Criteria:

- History of chronic HF (New York Heart Association [NYHA] Class II-IV) on standard therapy before qualifying HF decompensation - Previous HF hospitalization within 6 months prior to randomization or intravenous (IV) diuretic treatment for HF (without hospitalization) within 3 months. - Brain natriuretic peptide (BNP) levels: sinus rhythm-≥ 300 pg/mL; atrial fibrillation-≥ 500 pg/mL or N-terminal pro-Brain Natriuretic Peptide (NT- proBNP) levels: sinus rhythm- ≥ 1000 pg/mL; atrial fibrillation - ≥ 1600 pg/mL within 30 days prior to randomization - Left ventricular ejection fraction (LVEF) of <45% assessed within 12 months prior to randomization by any method - If female, is not of reproductive potential or agrees to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: practice abstinence from heterosexual activity or use (or have her partner use) acceptable contraception during heterosexual activity.

Protocol 1242-001-04 Exclusion Criteria: -Clinically unstable at the time of randomization as defined by either the administration of any IV treatment within 24 hours prior to randomization, and/or systolic blood pressure (SBP) -Current or anticipated use of long-acting nitrates or nitric oxide (NO) donors including isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil or transdermal nitroglycerin (NTG) patch, and molsidomine -Current or anticipated use of phosphodiesterase type 5 (PDE5) inhibitors such as vardenafil, tadalafil, and

Contact #s.: (+632) 8377534, (+632) 8377537, (+632) 8372071-80 loc. 2117, 2112 Saliksik Building, DOST Compound, Gen. Santos Ave., Bicutan Taguig City 1631 Philippines Page 3/6 sildenafil -Current use or anticipated use of a soluble guanylate cyclase (sGC) stimulator such as riociguat -Known allergy or sensitivity to any sGC stimulator -Awaiting heart transplantation (United Network for Organ Sharing Class 1A / 1B or equivalent), receiving continuous IV infusion of an inotrope, or has/anticipates receiving an implanted ventricular assist device -Primary valvular heart disease requiring surgery or intervention, or is within 3 months after valvular surgery or intervention -Hypertrophic obstructive cardiomyopathy -Acute myocarditis, amyloidosis, sarcoidosis, Takotsubo cardiomyopathy -Post-heart transplant cardiomyopathy -Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia -Acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction [NSTEMI], or ST elevation myocardial infarction [(STEMI]) or coronary revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]) within 60 days, or indication for coronary revascularization at time of randomization -Symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within 60 days

-Complex congenital heart disease

-Active endocarditis or constrictive pericarditis

-Estimated glomerular filtration rate (eGFR) -Severe hepatic insufficiency such as with hepatic encephalopathy

-Malignancy or other non-cardiac condition limiting life expectancy to -Current alcohol and/or drug abuse

-Participated in another interventional clinical study and treatment with another investigational product ≤30 days prior to randomization or plans to participate in any other trial/investigation during the duration of this study

-Mental or legal incapacitation and is unable to provide informed consent

-Immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is involved with this study

-Interstitial Lung Disease -Is pregnant or breastfeeding or plans to become pregnant or to breastfeed during the course of the study

STUDY TYPE

Interventional

INTERVENTION NAME

Drug: Vericiguat; 2.5, 5.0, or 10.0 mg orally once daily; Other Name: MK-1242; Drug: Placebo for Vericiguat; 2.5, 5.0, or 10.0 mg orally once daily

INTERVENTION DESCRIPTION

Assigned Interventions : - Drug: Vericiguat 2.5, 5.0, or 10.0 mg orally once daily Other Name: MK-1242 - Drug: Placebo for Vericiguat 2.5, 5.0, or 10.0 mg orally once daily

Contact #s.: (+632) 8377534, (+632) 8377537, (+632) 8372071-80 loc. 2117, 2112 Saliksik Building, DOST Compound, Gen. Santos Ave., Bicutan Taguig City 1631 Philippines Page 4/6

Arms: - Experimental: Vericiguat Starting dose of 2.5 mg taken orally once daily with food, on a background of standard of care. Dose will be uptitrated to 5 mg and to 10 mg. - Placebo Comparator: Placebo Starting dose of 2.5 mg taken orally once daily with food, on a background of standard of care. Dose will be uptitrated to 5 mg and to 10 mg.

AMENDMENT APPROVAL DATE/REASONS

Classification Approval Date Reason 2018-02-28 Amendments related to the protocol Due to a higher than projected number of primary composite events in the trial thus far, the futility analysis as originally proposed, would be conducted earlier than planned and would occur at a time when insufficient study follow-up was achieved to enable an adequate futility assessment. The primary purpose of the protocol amendment is to revise the interim futility analysis plan to ensure that adequate study follow-up will be achieved at the time when the futility analysis is conducted.The protocol was updated to indicate that the futility analysis will be performed at the same time as the efficacy interim analysis – when approximately 75% of the planned number of CV death events are observed (in the original plan, the futility analysis was to be performed at 50% of the planned number of primary composite events). In addition, CV death assessment has been added to the futility criteria to be consistent with the efficacy interim analysis approach. The analysis approach and futility bounds have been updated to take into consideration that more endpoint and longer follow-up data will be available at the time of the updated futility analysis compared to the previous approach. Additionally, since the study duration will be driven by the number of CV death events, clarification has been added that the actual observed number of primary endpoint events may differ from the expected number of events.

METHOD OF ALLOCATION

Randomized

MASKING / BLINDING

Double Blind

MASKING DETAILS

Double Blind (Subject, Investigator)

ASSIGNMENT

Parallel

Contact #s.: (+632) 8377534, (+632) 8377537, (+632) 8372071-80 loc. 2117, 2112 Saliksik Building, DOST Compound, Gen. Santos Ave., Bicutan Taguig City 1631 Philippines Page 5/6 PURPOSE

Treatment

PHASE

Phase III

RESEARCH UTILIZATION

Utilization Utilization Info No records Found.

Contact #s.: (+632) 8377534, (+632) 8377537, (+632) 8372071-80 loc. 2117, 2112 Saliksik Building, DOST Compound, Gen. Santos Ave., Bicutan Taguig City 1631 Philippines Page 6/6

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