Firibastat or Ramipril After Acute Myocardial Infarction for Prevention of Left Ventricular Dysfunction (QUORUM)

A Phase 2, Double-blind, Active-controlled, Dose-titrating Efficacy and Safety Study of Firibastat Compared to Ramipril Administered Orally, Twice Daily, Over 12 Weeks to Prevent Left Ventricular Dysfunction After Acute MI

This is a multicenter, randomized, double-blind, active-controlled, dose-titrating phase 2 study to evaluate the safety and efficacy of firibastat administered orally BID (2 daily doses) versus ramipril administered orally BID over 12 weeks after acute anterior MI.

Subjects will be followed for 12 weeks (over 4 study visits). A total of 294 male and female subjects with a diagnosis of first acute anterior MI will be randomized. The subjects will need to have a primary percutaneous coronary intervention (PCI) of the index MI related artery within 24 hours after MI.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction
• Intervention / Treatment: Drug: Firibastat; Drug: Ramipril

Detailed Description

At Inclusion Visit (Visit 2 [within 72 hours after acute MI]), subjects will be randomly assigned to 1 of the following 3 treatment groups in a 1:1:1 ratio:

• Group 1: Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks
• Group 2: Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks
• Group 3: Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks

Then subjects will undergo study procedures at Titration Visit (Visit 3 [Day 14]), Treatment Visit (Visit 4 Day 42]) and End-of-Treatment Visit (Visit 5 [Day 84]).

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bruno Besse, MD; Phone Number: +33 1 85 34 77 70; Email: bruno.besse@quantum-genomics.com
• Study Contact Backup: Name: Mariette Codou, PharmD; Phone Number: +33 (0)1 85 34 77 74; Email: mariette.codou@quantum-genomics.com

Study Locations

• France
  • Paris, France, 75013
    • Groupe Hospitalier Pitie-Salpêtrière - Institut de Cardiologie
• Germany
  • Kiel, Germany
    • UKSH Kiel
• Hungary
  • Budapest, Hungary
    • Central Hospital of Hungarian Army
• Poland
  • Kraków, Poland
    • Krakowski Szpital Specjalistyczny im. Jana Pawła II
• Slovakia
  • Bratislava, Slovakia
    • NUSCH Bratislava Dpt. of Acute Cardiology
• Spain
  • Madrid, Spain
    • Hospital La Paz,
• United Kingdom
  • Newcastle, United Kingdom
    • Freeman Hospital Newcastle upon Tyne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of first acute anterior MI (ST-elevation myocardial infarction) defined as chest pain >30 minutes and ST elevation ≥0.2 mV in at least 2 consecutive electrocardiogram (ECG) leads in the anterior area (DI, aVL, V1 V6).
• Primary PCI of the index-MI-related artery within 24 hours after the MI.

Exclusion Criteria:

• Body mass index >45 kg/m².
• Subject is hemodynamically unstable or has cardiogenic shock.
• Subjects with clinical signs of HF (Kilipp III and IV).
• Systolic blood pressure <100 mmHg at inclusion visit
• Early primary PCI of the index-MI-related artery performed within 3 hours after MI.
• Subjects treated with angiotensin-converting-enzyme inhibitor (ACE I), angiotensin receptor blocker (ARB) or sacubitril/valsartan prior to the index magnetic resonance imaging. Note: if treatment was for HTN, ACE I/ARB should be stopped, and, if necessary, another therapeutic class can be prescribed for HTN. If the ACE I/ARB was prescribed for congestive HF, the subject is not considered eligible; if the ACE I/ARB prescribed for another reason cannot be stopped, the subject is not eligible for study inclusion.
• Subjects scheduled for implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy, or pacemaker within the next 3 months. If an ICD is indicated for ventricular arrhythmia during the course of the study, a life vest, when possible, should be prescribed and the ICD scheduled after study completion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: firibastat 100 mg; Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks.	Drug: Firibastat; 1 or 2 capsules administered orally, twice daily; Other Names: QGC001
Experimental: Group 2: firibastat 500 mg; Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks.	Drug: Firibastat; 1 or 2 capsules administered orally, twice daily; Other Names: QGC001
Active Comparator: Group 3: ramipril 5 mg; Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks.	Drug: Ramipril; 1 or 2 capsules administered orally, twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricular Ejection Fraction Assessed by Cardiac Magnetic Resonance Imaging (CMRI)	Comparison of the effects of BID oral administration of 2 doses of firibastat to those of BID oral administration of ramipril on the change from Baseline in LVEF on Day 84	84 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left-ventricle End-diastolic Volume Assessed by CMRI	Comparison of the effects of BID administration of firibastat and ramipril on the change from Baseline to Day 84 in left-ventricle end-diastolic volume	84 days
Left-ventricle End-systolic Volume Assessed by CMRI	Comparison of the effects of BID administration of firibastat and ramipril on the change from Baseline to Day 84 in left-ventricle end-systolic volume	84 days
Major Cardiac Event (MACE): Combined Clinical Endpoint of Cardiovascular Death, MI, and Cardiac Hospitalization	Comparison of the effects of BID administration of firibastat and ramipril on major cardiac event (MACE) over 84 days	84 days
N-terminal Pro B-type Natriuretic Peptide (NT proBNP)	Comparison of the effects of BID administration of firibastat and ramipril on the change from Baseline to Day 84 in N-terminal pro b-type natriuretic peptide (NT proBNP)	84 days

Collaborators and Investigators

• Sponsor: Quantum Genomics SA
• Investigators: Principal Investigator: Gilles Montalescot, MD, PhD, Groupe Hospitalier Pitié-Salpêtrière - Paris

Publications and helpful links

General Publications

• Khosla J, Aronow WS, Frishman WH. Firibastat: An Oral First-in-Class Brain Aminopeptidase A Inhibitor for Systemic Hypertension. Cardiol Rev. 2022 Jan-Feb 01;30(1):50-55. doi: 10.1097/CRD.0000000000000360.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2019
• Primary Completion (Actual): July 8, 2021
• Study Completion (Actual): July 8, 2021

Study Registration Dates

• First Submitted: October 19, 2018
• First Submitted That Met QC Criteria: October 19, 2018
• First Posted (Actual): October 23, 2018

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Ventricular Dysfunction; Ventricular Dysfunction, Left; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Ramipril; Firibastat
• Other Study ID Numbers: QGC001-2QG4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No