Intracoronary Stenting and Antithrombotic Regimen: Lesion Platelet Adhesion as Selective Target of Endovenous Revacept

Study Overview
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Brief Summary
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The main objective is to evaluate the efficacy and safety of treatment with 2 doses (80 and 160 mg) of Revacept versus placebo in patients with stable coronary artery disease undergoing PCI.

Detailed Description
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Revacept is a protein that is made up of an Fc fragment (fragment crystallisable) fused to the GPVI receptor (the endogenous platelet collagen receptor). Consequently, Revacept binds to its ligand (collagen) on atherosclerotic plaques preventing circulating thrombocytes from binding to collagen exposed by the injured plaque. All this is achieved without affecting systemic hemostasis. Thus, blocking of GPVI-dependent pathways by interfering with vascular collagen sites is commonly seen as an attractive target for an anti-platelet therapy of atherosclerotic diseases.

Official Title
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Revacept, a Novel Inhibitor of Platelet Adhesion in Patients With Stable Coronary Artery Disease Undergoing Elective Percutaneous Coronary Interventions: a Phase II, Multicentre, Randomised, Double-blind and Placebo-controlled Study

Conditions
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Stable Coronary Artery Disease

Intervention / Treatment
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* Drug: Revacept 80 mg
* Drug: Revacept 160 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Men and women >18 years of age Diagnosis: Clinically stable coronary artery disease Angiographic evidence of coronary artery disease Indication for PCI Exclusion Criteria: WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for up to 4 weeks after receiving investigational product. Women who are pregnant or breastfeeding or are planning pregnancy during course of trial Women with a positive pregnancy test on enrolment or prior to investigational product administration. Patients with elevated high sensitivity cardiac troponin T levels at screening Patients receiving antithrombotic therapy with Prasugrel or Ticagrelor within 7 days prior to randomisation History of hypersensitivity, contraindication or serious adverse reaction to any component of the study drug (GPVI-Fc, sucrose, mannitol), acetylsalicylic acid or clopidogrel History of bleeding diathesis or active bleeding within the last 30 days Recent intracerebral haemorrhage or trauma within the last 3 months Thrombocytopenia (platelet count <30000/mm3) at screening Sustained hypertension (systolic BP >179mmHg or diastolic BP >109mmHg) at screening Renal failure (estimated glomerular filtration rate < 30ml/min and/or dialysis) Severe systemic disease, such as known malignancies or other comorbid conditions with life expectancy less than one year that may result in protocol non-compliance Unable to provide informed consent (e.g. severe dementia, or psychosis) Current severe liver dysfunction (transaminase level >5-fold the upper normal range limit) Patients with an indication for anticoagulant therapy Participation in any other clinical interventional trial (drug/device) within less than 30 days prior to screening Any other contraindication to perform PCI Any planned additional PCI or surgery within 30 days after randomization Suspected poor capability to follow instructions and cooperate Prisoners or subjects who are involuntarily incarcerated Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness (e.g. infectious disease)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: with 2 doses (80 and 160 mg) of Revacept versus placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Revacept 80 mg<br>single dose, intravenous | Drug: Revacept 80 mg<br>* single dose, intravenous application of 80 mg Revacept<br>|
| Experimental: Revacept 160 mg<br>single dose, intravenous | Drug: Revacept 160 mg<br>* single dose, intravenous application of 180 mg Revacept<br>|
| Placebo Comparator: Placebo<br>single dose, intravenous | Drug: Placebo<br>* single dose, intravenous application of Placebo solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint-composite endpoint of death and myocardial injury | A composite endpoint of death or myocardial injury (defined as increase in cardiac biomarker - high sensitivity cardiac troponin T of at least 5 times the upper limit of norm (ULN) within 48 hours from randomisation). | within 48 hours from randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality | All cause mortality | within 30 days after randomisation | 
| Myocardial infarction | Myocardial infarction | within 30 days after randomisation | 
| PCI-related (type 4) myocardial infarction | PCI-related (type 4) myocardial infarction | within 30 days after randomisation | 
| Definite stent thrombosis | Definite stent thrombosis | within 30 days after randomisation | 
| Urgent coronary revascularization | Urgent coronary revascularization | within 30 days after randomisation | 
| Stroke | Stroke | within 30 days after randomisation | 
| Peak potprocedural high-sensitivity troponin T level | Peak potprocedural high-sensitivity troponin T level | within 48 hours after randomisation | 
| Bleeding class 2 or higher according to Bleeding Academic Research Consortium (BARC) criteria (safety endpoint) | Bleeding class 2 or higher according to Bleeding Academic Research Consortium (BARC) criteria (safety endpoint) | within 30 days after randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary artery disease, platelet inhibition