Comparative Study of ALX-0081 Versus GPIIb/IIIa Inhibitor in High Risk Percutaneous Coronary Intervention (PCI) Patients

This is a multicenter, randomized and open-label Phase II study to compare the safety, tolerability and biological effectiveness of ALX-0081 versus the GPIIb/IIIa inhibitor ReoPro® in high risk PCI patients.

Patients will receive standard treatment with acetylsalicylic acid (ASA) plus clopidogrel and heparin. Eligible patients will be randomly assigned to receive open-label study treatment with either ALX-0081 or ReoPro®. Patients will be stratified according to PCI type (elective or ad-hoc) and stent type (bare metal stent or drug eluting stent).

• Unstable Angina
• Non ST Segment Elevation Myocardial Infarction (NSTEMI)
• Stable Angina (Associated With High Risk PCI)

• Drug: ALX-0081
  4 i.v. bolus injections, once every 6 hours; first dose of 6 mg, three subsequent doses of 4 mg
• Drug: ReoPro®
  0.25 mg/kg i.v. bolus injection followed by continuous i.v. infusion of 0.125 µg/kg/min (to a max. of 10 µg/min) for 12 hours

• Experimental: ALX-0081
  Intervention: Drug: ALX-0081
• Active Comparator: GPIIb/IIIa inhibitor
  Intervention: Drug: ReoPro®

Inclusion Criteria:

• Have unstable angina or NSTEMI,or stable angina with at least 2 factors indicating a high risk PCI as follows: patient related: diabetic patients, renal failure (glomerular filtration rate < 60), reduced left ventricular ejection fraction < 35%, age > 75 years, female gender and/or lesion/anatomy related: SYNTAX score > 26, bifurcation lesions, multi-vessel disease, intracoronary thrombus.
• Adequate hematological function including platelets > 100000/mm3.
• Body mass index (BMI) ≥18 kg/m2 and ≤ 35 kg/m2.
• Aged ≥ 18 years old.
• Women of childbearing potential must be practicing a medically acceptable contraceptive regimen. Only males who do not want to father children during the study and in the first 4 months after treatment may be included in the study. During this period, safe contraception is mandatory. Male patients who are sexually active must use a condom during intercourse and ensure that the female partner uses a reliable contraceptive method, or they must refrain from sexual intercourse during the first 4 months after treatment.
• Patients must be accessible for follow-up.
• Have a sufficient command to read and understand all instructions necessary for giving informed consent and participating in the study.
• Have signed and dated written informed consent prior to any study-related procedures.

Exclusion Criteria:

• Previous (within 30 days) treatment with GPIIb/IIIa inhibitors (such as ReoPro®).
• ST-elevation myocardial infarction (STEMI).
• Chronic total occlusion of a coronary artery.
• Scheduled rotablator procedure.
• PCI of the arterial or venous by-pass graft.
• Any contra-indication for ReoPro®.
• Major organ dysfunction, infection or any serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
• Known hypersensitivity to human/humanized antibodies.
• Women who are pregnant or lactating.
• Dementia or significantly altered mental status that would prohibit understanding the study procedures and giving informed consent.
• Use of vitamin K antagonists and/or Factor Xa inhibitors within 4 weeks prior to admission to the Hospital Intensive Care Unit.
• Use of GPIIa/IIIb inhibitors other than ReoPro®; prasugrel, bivalirudin and fondaparinux prior to and throughout the study.
• Known history of acquired or congenital bleeding disorder, coagulopathy or platelet disorder.
• Evidence of active pathological bleeding at screening or history of clinically significant bleeding (such as gastrointestinal or genitourinary) within the last 6 months prior to screening visit, unless the cause has been definitely corrected
• History of intracranial bleeding (e.g. hemorrhagic stroke, subdural hematoma, subarachnoid hemorrhage) or history of hemorrhagic retinopathy.
• History of ischemic stroke or TIA, within the past year prior to screening or known structural cerebral vascular lesion (e.g. arteriovenous malformation, aneurysm).
• History of New York Heart Association class III or IV congestive heart failure or history of severe, uncontrolled cardiac arrhythmias at screening.
• Planned elective surgical operation or major invasive procedures or traumas from 30 days prior to screening to completion of the study at Day 30 (the decision of what constitutes a major invasive procedure or trauma will be at the discretion of the investigator in conjunction with review and approval by the Medical Monitor).
• Use of another investigational drug or device within previous 30 days (12 weeks for investigational devices, e.g. unapproved stents) prior to screening.