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

Study Overview
=================
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]).

Official Title
-----------------
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

Conditions
-----------------
Myocardial Infarction

Intervention / Treatment
-----------------
* Drug: Ramipril
* Drug: Firibastat


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

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 |