The treatment of acute myocardial infarction, AMI is aimed at enabling the return of blood flow to the ischemic myocardium, thereby limiting the size of the infarct. However the reperfusion by itself causes additional damage to the myocardium. Reducing the size of the myocardial infarct can minimize the risk of heart failure and death. MedDRA version: 16.1 Level: PT Classification code 10063837 Term: Reperfusion injury System Organ Class: 10047065 - Vascular disorders MedDRA version: 16.1 Leve
Conditions
Interventions
Product Name: danegaptide
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Danegaptide
CAS Number: 943134-39-2
Current Sponsor code: ZP1609
Other descriptive name: 1-(2-aminoa
Sponsors
Zealand Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients will be entered into this trial only if they meet all of the following criteria: 1. Men or women of minimum 18 years of age 2. STEMI as characterized by one of following: a. minimum 2 mV ST-segment elevation in 2 or more leads (V1 through V4) b. presumed new left bundle branch block with minimum of 1 mV concordant ST segment elevation c. minimum 1 mV ST-segment elevation in 2 or more limb leads (II, III and aVF, I, aVL) d. minimum 1mV ST segment elevation in 2 or more leads (V4-V6) 3. Clinical ischemic symptoms consistent with acute myocardial infarction (MI) for a maximum of 12 hours prior to percutaneous coronary intervention (PCI) 4. Women of childbearing potential must during the past 3 months have used an acceptable method of contraception to avoid pregnancy (hormonal contraceptives, intrauterine device or double barrier method (male condom plus diaphragm) and agree to use it throughout the study or practice sexual abstinence. Note: A woman of childbearing potential is defined as any female: a. who is not postmenopausal (defined as women over the age of 50 who have been amenorrheic for at least 12 consecutive months) b. who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) 5. Willingness and ability to provide written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
Exclusion criteria: 1. Current participation or participation within the past 30 days in any other investigational study 2. Women who are pregnant or breastfeeding or who plan on becoming pregnant during the study 3. Known prior MI in same area as present STEMI, known conclusive hypertrophic or dilated cardiomyopathy, or prior hospital admission for heart failure 4. More than 12 hours between the onset of symptoms of acute MI and anticipated revascularization 5. Anticipated requirement, as assessed prior to randomization, for a staged treatment of coronary artery disease or other interventional or surgical procedures to treat heart disease (e.g., valve replacement, PCI, or coronary artery bypass graft) planned or scheduled to take place within 6 months after the investigational agent infusion 6. Receipt of any thrombolytic agent since onset of acute MI symptoms 7. Cardiogenic shock or hemodynamic instability within 24 hours prior to randomization, except brief VF that has been successfully cardioverted 8. Prior PCI or CABG of same coronary artery as present STEMI 9. Known contraindication to cardiac magnetic resonance imaging (MRI) such as significant claustrophobia, severe allergy to gadolinium chelate contrast, severe renal insufficiency (defined as estimated glomerular filtration rate [eGFR] less than 30 mL/min/1.73 m2), presence of MRI contraindicated implanted devices (e.g., pacemaker, implanted cardiac defibrillator, cardiac resynchronization therapy device, cochlear implant), imbedded metal objects (e.g. shrapnel), or any other contraindication for cardiac MRI 10. Known active malignancy with an expected life-expectancy of less than 2 years 11. Previous enrolment in this study 12. Any concurrent condition, which, in the opinion of the investigator, would make the patient unsuitable for participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare the efficacy of two dose levels of Danegaptide to placebo when added to the standard treatment of STEMI in patients with single vessel disease having TIMI flow 0 or 1 prior to PCI conducted within 6 hours of symptoms debut.;Secondary Objective: - To explore the efficacy of two dose levels of Danegaptide compared to placebo when added to the standard treatment of STEMI patients - To explore additional functional, pharmacodynamic and clinical effects of Danegaptide when added to the standard treatment of STEMI patients. - To describe pharmacokinetic parameters (PK) of Danegaptide - To describe the safety of two dose levels of Danegaptide relative to placebo when added to the standard treatment of STEMI patients ;Primary end point(s): The primary efficacy endpoint is Myocardial Salvage Index (MSI) measured at Day 90. MSI is assessed by cMRI and is calculated as the relative change, from baseline to day 90, in myocardial volume at risk MSI is defined as: MSI = (AAR (g) – Final Infarct Size (g))/AAR (g) where AAR (Area at Risk) is assessed as oedema visualized and measured by cMRI using T2 weighted short tau inversion-recovery sequence at Day 2, and Final Infarct Size is assessed as hyper-enhanced myocardial tissue visualized and measured by cMRI using gadolinium-enhanced images at Day 90. ;Timepoint(s) of evaluation of this end point: Day 2 (48-72 hours) Magnetic Resonnance Imaging for AAR assessment and day 90 MRI for Final Infarct Size. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary MRI parameters: - Relative infarct size ((%) [infarct size/left ventricle (LV) size (g/g)] × 100), as assessed by LGE cMRI, at Day 90 - Relative infarct size (%) at baseline and change in infarct size from baseline to Day 90 - Absolute infarct size (g) and change in absolute infarct size at baseline and Day 90 - Left ventricular ejection fraction (LVEF) at baseline and Day 90 and change in LVEF from baseline to Day 90 - Change in LV wall thickness of all segments at end diastole and end systole from baseline to Day 90 - Change in left ventricular end-systolic volume (LV-ESV) as measured by cMRI from baseline to Day 90 - Change in left ventricular end-diastolic volume (LV-EDV) as measured by cMRI from baseline to Day 90 - Relative volume with microvascular obstruction (MVO) as assessed by cMRI at Day 2 - Relative volume with infarct haemorrhage by cMRI at Day 2 Secondary Efficacy Endpoints (Non-imaging): - 90-day clinical outcome/MACE [cardiac death, new or worsening heart failure (during the initial hospitalization) and re-hospitalization due to heart failure] - Occurrence of arrhythmias during hospitalization and hospitalization for arrhythmias during the follow-up period - Degree of ST-resolution and fraction of patients with = 70% ST-resolution measured 60 minutes post-PCI procedure - Infarct size, as assessed by area under the plasma concentration-time curve (AUC 0-48 hours) for creatine kinase-MB and TnT - TIMI-flow as assessed immediately after the PCI procedure - Adverse events incl. all cause mortality, stroke, arrythmias and ICD implantation -Quality of Life assessment according to SF-36 and EQ-5D Secondary PK Endpoints: - Plasma concentration of Danegaptide at the end of the PCI procedure - Post infusion plasma concentration of Danegaptide (7-12 hours) - Estimated half-life and clearance of Danegaptide - Estimated volume of distribution at steady state (Vss) based on the plasma concentration of Dan | — |
Countries
Denmark
Contacts
Public ContactUlrik Mouritzen
Zealand Pharma a/s
Outcome results
None listed