A Phase 2a Trial to Evaluate the Safety, Tolerability and Efficacy of Intravenous MTP-131 on Reperfusion Injury in Patients Undergoing Primary Percutaneous Coronary Intervention and Stenting for ST-segment Elevation Myocardial Infarction Infarction
Overview
- Phase
- Phase 2
- Intervention
- Bendavia (MTP-131)
- Conditions
- Reperfusion Injury
- Sponsor
- Stealth BioTherapeutics Inc.
- Enrollment
- 300
- Locations
- 30
- Primary Endpoint
- Area Under the Curve (AUC) of Serum Creatine Kinase Isoenzyme Type Muscle-brain (CK-MB)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The EMBRACE-STEMI trial was a Phase 2a prospective, multicenter, multinational randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and efficacy of IV administered elamipretide (also known as MTP-131, or Bendavia) on a background of standard-of-care therapy for reduction of reperfusion injury in patients with first time acute, anterior wall ST-segment elevation myocardial infarction (STEMI).
Detailed Description
The EMBRACE-STEMI trial was a Phase 2a prospective, multicenter, multinational randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and efficacy of IV administered elamipretide on a background of standard-of-care therapy for reduction of reperfusion injury in patients with first time acute, anterior wall STEMI. Patients were randomized to receive either an infusion of elamipretide at 0.05 mg/kg/hr or an identically appearing placebo administered as an IV infusion at 60 mL/hr. The infusion began at least 15 minutes but no more than 1 hour prior to the anticipated reperfusion event and continued through approximately 1 hour following re-establishment of blood flow through the culprit vessel. The reduction of reperfusion injury, or infarct size, was estimated using the area under the curve (AUC) of the serum creatine kinase (CK) isoenzyme, as well as using magnetic resonance imaging (MRI) performed on the Day 4±1 and on Day 30±7 (both MRI assessments measured infarct size and the ratio of infarct size to myocardial mass). The analyses of cardiac MRI data were performed for both the primary endpoint population and also in all patients who had adequate Day 4/Day 30 cardiac MRI studies. After completion of the percutaneous coronary intervention (PCI) and stenting, patients received standard medical treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 and \<85 years
- •The patient presents with first-time acute, anterior wall STEMI scheduled to undergo primary PCI and stenting.
- •The patient has symptoms of cardiac ischemia of ≥10 minutes.
- •The patient must demonstrate an anterior wall STEMI with \>0.1 millivolt (mV) ST-segment elevation in at least two contiguous precordial leads (i.e., V1-V4) or presumed new left bundle branch block.
- •The time from onset of symptoms of cardiac ischemia to the anticipated time of initial PCI balloon inflation does not exceed four (4) hours and it is anticipated that the door-to-balloon time will be \<2 hours.
- •For female patients of child-bearing potential, an adequate form of contraception must be adhered to prior to entry into the study and for a further 3 months after the follow-up visit. Female patients of childbearing potential must have a negative serum pregnancy test prior to entry into the study.
- •Female patients not of childbearing potential (i.e. female patients who are postmenopausal since last regular menses, or have been surgically sterilized at least 1 year prior to screening visit) are eligible to enter the study.
- •For male patients with female partners of child-bearing potential, an adequate form of contraception must be adhered to prior to entry into the study and for a further 3 months after the post-study medical.
- •Written informed consent obtained that strictly adheres to the written guidelines from the local Institutional Review Board (IRB)/ Ethical Committee (EC).
- •Exclusion Criteria
Exclusion Criteria
- Not provided
Arms & Interventions
Bendavia™
Bendavia™ administered intravenously at 0.05 mg/kg/hr at least 15, but no more than 60 minutes, prior to the anticipated time of the PCI, and continued for 1 hour after re-establishment of blood flow through the culprit vessel.
Intervention: Bendavia (MTP-131)
Placebo
Placebo administered intravenously at 60 mL/hr at least 15, but no more than 60 minutes, prior to the anticipated time of the PCI, and continued for 1 hour after re-establishment of blood flow through the culprit vessel.
Intervention: Placebo
Outcomes
Primary Outcomes
Area Under the Curve (AUC) of Serum Creatine Kinase Isoenzyme Type Muscle-brain (CK-MB)
Time Frame: The initial 24 and 72 hours post-percutaneous coronary intervention (PCI)
Infarct size as measured by the AUC of serum CK-MB at 24 and 72 hours post-PCI
Secondary Outcomes
- AUC of Troponin 1 Enzyme(Initial 24 and 72 hours post-PCI)
- Thrombosis in Myocardial Infarction (TIMI) Perfusion Grade Flow at Completion of PCI(Initiation to Completion of PCI, no longer than 4 hours)
- Change in Serum Creatinine From Baseline(Day 30 +7)
- Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline(Day 30 +/- 7)
- Blood Urea Nitrogen (BUN) Change From Baseline(Baseline to Day 30)
- Immediate Myocardial Complications: Mechanical Complications(Baseline up to 1 hour post-PCI)
- Ratio of Volume of Infarcted Myocardium to Left Ventricular Mass(Day 30 + 7)
- Corrected TIMI Frame Count(Completion of PCI, no longer than 4 hours)
- ST-Segmented Elevation From Pre-PCI to 24 Hours Post-PCI and Presence of ST-Segmented Resolution(pre-PCI to 24 hours post-PCI)
- Cystatin C Change From Baseline(Day 30 + 7)
- Immediate Myocardial Complications: Ventricular Tachycardia or Fibrillation(Baseline up to 1 hour post-PCI)
- Emergency Use of Medications During PCI Procedure(Initiation to Completion of PCI, no longer than 4 hours)
- Number and Percent of Grade 1 Episode of Contrast-Induced Nephropathy Post-PCI(Baseline to 48 hours post PCI or MRI)
- High Sensitivity C-Reactive Protein (hsCRP): Change From Baseline to Day 30(Baseline to Day 30)
- ProB-type Natriuretic Peptide (NT-proBNP) Change From Baseline to Day 30(Baseline to Day 30)
- Left Ventricular (LV) Ejection Fraction (%)(Day 4 to Day 30)
- Difference Between Left Ventricular End Diastolic Volume, Corrected(Day 4 and Day 30)
- Difference Between Left Ventricular End Systolic Volume, Corrected(Day 4 and Day 30)
- Chronic Heart Failure(Within 24 hours after PCI)