A study of the efficacy of POL6326 in treating patients following a heart attack

• Conditions: Acute Myocardial Infarction; MedDRA version: 18.0Level: LLTClassification code 10064345Term: ST segment elevation myocardial infarctionSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2012-003229-91-HU
• Lead Sponsor: Polyphor AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-04-02
• Last Update Posted: 16 November 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

1. Patients must present with symptoms suggestive of an acute MI with ST-segment elevation =1 mm in at least 2 contiguous leads or new left bundle-branch block. It is possible that the ECGs of STEMI patients presenting late within the 48 hour time window may no longer show any ST-segment elevations. Instead, they may have already developed other ECG patterns (e.g., new Q-waves with T-wave inversion). These patients can also be included in the trial as long as they meet the following criteria:
• They must have a high-grade stenosis or total occlusion on angiography, associated with abnormalities in regional wall motion AND
• A rise and/or fall in cardiac necrosis biomarkers upon serial measurements with at least one value above the 99th percentile of the upper reference limit (preferably, troponin).

2. Patients must be scheduled to undergo coronary angiography for the purposes of primary PCI culminating in successful stent implantation as determined by Thrombolysis in Myocardial Infarction (TIMI) grade 2 or 3 preferably within 24 hours, but up to 48 hours after the onset of their symptoms. Use of a bare-metal stent or drug-eluting stent will be at the discretion of the interventional cardiologist. Patients who have had previous PCI for medical reasons other than STEMI or NSTEMI are eligible as long as they meet the other eligibility criteria.

3. Patients will be males or females =18 and =80 years of age, inclusive.
• Male patients with a female partner of childbearing potential and female patients of childbearing potential must be willing to use a condom, diaphragm or cervical vault cap in conjunction with spermicidal foam, gel, film, cream, or suppository from the time of first dose until 3 months after the last dose of IMP. Female patients will also be requested to use an additional highly effective form of contraception (e.g., placement of an effective hormonal intra-uterine device i.e. Mirena® coil; use of oral injected or implanted hormonal methods of contraception) from the time of first dose until 3 months after the last dose of IMP.
• Female patients of non-childbearing potential must be postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy or confirmed tubal occlusion (not tubal ligation). Postmenopausal is defined as no menses for at least 1 year, or a follicle stimulating hormone (FSH) level >40 IU/L, unless the patient is taking hormone replacement therapy.

4. Patients must have an LVEF =45% as determined by Investigator assessment of baseline cardiac MRI.

5. Patients must not have had any previous occurrence of MI as assessed by clinical history and baseline cardiac MRI.

6. Patients must have an estimated glomerular filtration rate (eGFR) =40 mL/minute prior to MRI, as determined by the Cockroft-Gault formula:
[(140 – age) * (weight in kg) * (0.85 if female)] / [72 * serum creatinine in mg/dL]

7. Patients will have given their written informed consent to participate in the study.
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 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

1. If there is, in the physician’s opinion, evidence of multi-vessel coronary artery disease likely to require repeat PCI or coronary artery bypass grafting within 4 months after randomisation.

2. Patients with pulmonary oedema or cardiogenic shock requiring intubation or mechanical support at the time of the planned baseline MRI.

3. Fitted with a non-MRI-compatible cardiac pacemaker or implantable cardioverter defibrillator, or expected to require such a device within 4 months after randomisation.

4. Terminal illness or malignant disease.

5. Advanced hepatic disease as determined by the following laboratory values:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and total bilirubin >2x ULN or international normalised ratio >1.5 or,
• ALT or AST >3x ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash or eosinophilia.

6. Renal disease whereby eGFR is <40 mL/minute, as determined by the Cockroft-Gault formula (see Inclusion Criterion 6).

7. Diagnosis of severe obesity which precludes MRI assessments.

8. Suffering from claustrophobia.

9. Acute systemic infection or fever.

10. Anaemia (where haemoglobin levels are <10 g/dL), thrombocytopaenia (platelet count <100000/µL) or coagulopathy.

11. Patients with a history of multiple drug allergies or with a known allergy to the drug class of CXCR4 antagonists.

12. Pregnancy or females of childbearing potential who are not using double contraception.

13. Known history of human immunodeficiency virus (HIV) infection, chronic hepatitis B or hepatitis C infection or significant active chronic inflammatory disease that requires immunosuppressive medication or regular systemic corticosteroids.

14. Patients who have participated in any investigational drug or device trial within 30 days prior to signing informed consent.

15. Patients who are unwilling or unable to abide by the study requirements.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the effects of the CXCR4 antagonist POL6326 on cardiac function and infarct size in patients with large reperfused STEMI.;Secondary Objective: • To determine the safety and tolerability of POL6326 following 2-hour IV infusions in patients with large reperfused STEMI.<br><br>• To determine the pharmacokinetic profile of POL6326 in plasma following 2-hour IV infusions in patients with large reperfused STEMI.;Primary end point(s): The primary endpoint is:<br><br>• Group mean difference of intra-individual changes in global LVEF from baseline to 4 months, as determined by cardiac MRI. The baseline MRI is conducted at screening on Day 2 or Day 3;Timepoint(s) of evaluation of this end point: The primary endpoint is assessed at 4 months.