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

NCT ID: NCT03715998

Last Updated: 2023-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 295 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-04
• Study Completion Date: 2021-07-08

Brief Summary

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.

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]).

Conditions

Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1: firibastat 100 mg

Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks.

Group Type: EXPERIMENTAL

Firibastat

Intervention Type: DRUG

1 or 2 capsules administered orally, twice daily

Group 2: firibastat 500 mg

Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks.

Group Type: EXPERIMENTAL

Firibastat

Intervention Type: DRUG

1 or 2 capsules administered orally, twice daily

Group 3: ramipril 5 mg

Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks.

Group Type: ACTIVE_COMPARATOR

Ramipril

Intervention Type: DRUG

1 or 2 capsules administered orally, twice daily

Interventions

Ramipril

1 or 2 capsules administered orally, twice daily

Intervention Type: DRUG

Firibastat

1 or 2 capsules administered orally, twice daily

Intervention Type: DRUG

Other Intervention Names

QGC001

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quantum Genomics SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilles Montalescot, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Groupe Hospitalier Pitié-Salpêtrière - Paris

Locations

Groupe Hospitalier Pitie-Salpêtrière - Institut de Cardiologie

Paris, , France

UKSH Kiel

Kiel, , Germany

Central Hospital of Hungarian Army

Budapest, , Hungary

Krakowski Szpital Specjalistyczny im. Jana Pawła II

Krakow, , Poland

NUSCH Bratislava Dpt. of Acute Cardiology

Bratislava, , Slovakia

Hospital La Paz,

Madrid, , Spain

Freeman Hospital Newcastle upon Tyne

Newcastle, , United Kingdom

Countries

France; Germany; Hungary; Poland; Slovakia; Spain; United Kingdom

References

Montalescot G, Alexander JH, Cequier-Fillat A, Solomon SD, Redheuil A, Hudec M, Silvain J, Kachenoura N, Janas A, Orban M, Josse I, Balavoine F, Besse B. Firibastat Versus Ramipril After Acute Mechanical Reperfusion of Anterior Myocardial Infarction: A Phase 2 Study. Am J Cardiovasc Drugs. 2023 Mar;23(2):207-217. doi: 10.1007/s40256-023-00567-8. Epub 2023 Feb 9.

Reference Type: DERIVED

PMID: 36757536 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33027067 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

QGC001-2QG4

Identifier Type: -

Identifier Source: org_study_id