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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: December 31, 2020

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]).

Interventions

  • Drug: Ramipril
    • 1 or 2 capsules administered orally, twice daily
  • Drug: Firibastat
    • 1 or 2 capsules administered orally, twice daily

Arms, Groups and Cohorts

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

Clinical Trial Outcome Measures

Primary Measures

  • Left ventricular ejection fraction assessed by cardiac magnetic resonance imaging (CMRI)
    • Time Frame: 84 days
    • 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

Secondary Measures

  • Left-ventricle end-diastolic volume assessed by CMRI
    • Time Frame: 84 days
    • 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
  • Left-ventricle end-systolic volume assessed by CMRI
    • Time Frame: 84 days
    • 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
  • Major cardiac event (MACE): combined clinical endpoint of cardiovascular death, MI, and cardiac hospitalization
    • Time Frame: 84 days
    • Comparison of the effects of BID administration of firibastat and ramipril on major cardiac event (MACE) over 84 days
  • N-terminal pro b-type natriuretic peptide (NT proBNP)
    • Time Frame: 84 days
    • 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)

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Quantum Genomics SA
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Gilles Montalescot, MD, PhD, Principal Investigator, Groupe Hospitalier Pitié-Salpêtrière – Paris
  • Overall Contact(s)
    • Bruno Besse, MD, +33 1 85 34 77 70, bruno.besse@quantum-genomics.com

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.