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

NCT03715998 | Completed Phase 2 Results DMC

• 1 other identifier: QGC001-2QG4
• Study Type: interventional
• Target: 295
• Locations: 7 countries
• Sites: 7

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.

Conditions

Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Left-ventricle End-diastolic Volume Assessed by CMRI

  84 days

• Left-ventricle End-systolic Volume Assessed by CMRI

  84 days

• Major Cardiac Event (MACE): Combined Clinical Endpoint of Cardiovascular Death, MI, and Cardiac Hospitalization

  84 days

• N-terminal Pro B-type Natriuretic Peptide (NT proBNP)

  84 days

Study Arms (3)

Group 1: firibastat 100 mg

EXPERIMENTAL

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

Drug: Firibastat

Group 2: firibastat 500 mg

EXPERIMENTAL

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

Drug: Firibastat

Group 3: ramipril 5 mg

ACTIVE COMPARATOR

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

Drug: Ramipril

Interventions

Ramipril DRUG

1 or 2 capsules administered orally, twice daily

Group 3: ramipril 5 mg

Firibastat DRUG

1 or 2 capsules administered orally, twice daily

Also known as: QGC001

Group 1: firibastat 100 mg; Group 2: firibastat 500 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Body mass index \>45 kg/m².
• Subject is hemodynamically unstable or has cardiogenic shock.
• Subjects with clinical signs of HF (Kilipp III and IV).
• Early primary PCI of the index-MI-related artery performed within 3 hours after MI.
• 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.

Sponsors & Collaborators

• Quantum Genomics SA: lead

Study Sites (7)

Groupe Hospitalier Pitie-Salpêtrière - Institut de Cardiologie

Paris, 75013, France

Location

UKSH Kiel

Kiel, Germany

Location

Central Hospital of Hungarian Army

Budapest, Hungary

Location

Krakowski Szpital Specjalistyczny im. Jana Pawła II

Krakow, Poland

Location

NUSCH Bratislava Dpt. of Acute Cardiology

Bratislava, Slovakia

Location

Hospital La Paz,

Madrid, Spain

Location

Freeman Hospital Newcastle upon Tyne

Newcastle, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 36757536 DERIVED

• 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.

  PMID: 33027067 DERIVED

MeSH Terms

Conditions

Myocardial Infarction

Interventions

Ramipril; firibastat

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr Bruno Besse
• Organization: Quantum Genomics

bruno.besse@quantum-genomics.com

+33 1 85 34 77 73

Study Officials

• Gilles Montalescot, MD, PhD

  Groupe Hospitalier Pitié-Salpêtrière - Paris

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2018
• First Posted: October 23, 2018
• Study Start: June 4, 2019
• Primary Completion: July 8, 2021
• Study Completion: July 8, 2021
• Last Updated: February 27, 2023
• Results First Posted: February 27, 2023

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); DE (1); GB (1); SL (1); ES (1); PL (1); HU (1)