COBRA PZF™ Coronary Stent for Early Healing, Thrombus Inhibition, Endothelialization and Avoiding Long-Term DAPT

COBRA PZF™ Coronary Stent System in Native Coronary Arteries for Early Healing, Thrombus Inhibition, Endothelialization and Avoiding Long-Term Dual Anti-Platelet Therapy. The PzF Shield Trial

This is a prospective, multi-center, non-randomized, single arm clinical trial that will be conducted at up to 40 sites in the United States and Outside United States (OUS). This study will enroll patients with symptomatic ischemic heart disease due to a single de novo lesion contained within a native coronary artery with reference vessel diameter between 2.5 mm and 4.0 mm and lesion length ≤ 24 mm that is amenable to percutaneous coronary intervention (PCI) and stent deployment. All patients will be followed at 30 days, 6 months, 9 months, 1 year and annually for 5 years post index stenting procedure.

The main objective of this study is to evaluate the safety and effectiveness of the COBRA PzF™ Coronary Stent System in the treatment of de novo lesions in native coronary arteries. The primary endpoint will be the incidence of target vessel failure (TVF, see definition below) within 270 days of treatment with the COBRA PzFTM Coronary Stent System. This rate will be compared to a performance goal derived using a meta-analysis from published historical data of the standard-of-care therapy, coronary stenting with bare metal stents.

PRIMARY STUDY HYPOTHESIS The CeloNova COBRA PzFTM Study will have a primary endpoint (TVF) rate less than 19.62% and by that will meet the performance goal for bare metal stents, per the results of the historical control group combined with relevant data for EXPRESS™, Driver™, Presillion/Presillion plus™ and NIRFLEX™ stents.

SECONDARY STUDY HYPOTHESIS The powered secondary endpoint for this trial is that the CeloNova COBRA PzFTM Study will have a 9-month in-stent late loss (LL) that meets or is lower than the performance goal of 1.1 mm.

NUMBER OF PATIENTS 296 patients will be enrolled to account for loss to follow-up, which is estimated to be approximately 5% (resulting in 281 evaluable patients), at up to 40 sites in United States and OUS. At least 40% of subjects will be enrolled in the United States.

PRIMARY ENDPOINT Target vessel failure (TVF), defined as cardiac death, target vessel myocardial infarction (MI) [Q wave or non-Q wave, ARC-definition], or clinically driven target vessel revascularization (TVR) by percutaneous or surgical methods within 270 days post-procedure.

SECONDARY ENDPOINTS

1. All Death at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days

2. Cardiac Death at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days

3. Major Adverse Cardiac Events (MACE), defined as cardiac death, MI (Q wave and non-Q wave), emergent bypass surgery, or clinically driven target lesion revascularization (TLR) by percutaneous or surgical methods at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days

4. MI at 30, 180 and 270, 360, 720, 1080, 1440, and 1800 days CeloNova Biosciences, Inc. Confidential CeloNova COBRA PzF™ Study Protocol # COBRA 2012-01 6 07 May 14

5. Clinically driven TLR at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days

6. Stroke (ischemic and hemorrhagic) at 30, 180, 270 and 360 days

7. Clinically driven TVR at 30, 180, 270 and 360 days

8. Composite Endpoint of Cardiac Death and MI at 30, 180, 270, and 360 days

9. TVF at 30, 180, and 360 days

10. Acute Success Rates

    1. Device Success: Attainment of < 30% final residual stenosis of the target lesion using only the COBRA PzFTM Coronary Stent System.
    2. Lesion Success: Attainment of < 30% final residual stenosis of the target lesion using any percutaneous method.
    3. Procedure Success: Attainment of < 30% final residual stenosis of the target lesion and no in-hospital MACE.

11. Bleeding or Vascular Complications at hospital discharge

12. Early Stent Thrombosis (ARC defined) at 30 days

13. Late Stent Thrombosis at 180, 270, and 360 days

14. Angiographic Endpoints (on first 90 evaluable patients) at 270 days (after clinical assessment)

    1. In-stent late loss (Secondary Endpoint hypothesis)
    2. In-segment percent diameter stenosis (%DS) (within the 5 mm margins proximal and distal to stent)
    3. In-stent percent diameter stenosis (%DS)
    4. In-segment late loss
    5. In-segment binary restenosis (stenosis of > 50% of the reference vessel diameter)
    6. In-stent binary restenosis
    7. In-stent minimum lumen diameter (MLD)
    8. In-segment MLD
    9. Longitudinal stent deformation
    10. Stent fracture

15. Optical Coherence Tomography Endpoints (on 45 subjects) at 270 days (after clinical assessment)

    1. in-stent neointimal thickness (NT)
    2. Lumen area
    3. Lumen volume
    4. Stent area
    5. Stent volume
    6. Proportion of uncovered and/or malopposed struts
    7. Stent fracture

General Inclusion Criteria:

1. Patient >/= to 18 years old.
2. Eligible for percutaneous coronary intervention (PCI).
3. Patient understands the nature of the procedure and provides written informed consent prior to the catheterization procedure.
4. Patient is willing to comply with specified follow-up evaluation and can be contacted by telephone.
5. Acceptable candidate for coronary artery bypass graft (CABG) surgery.
6. Stable angina pectoris (Canadian Cardiovascular Society (CCS) 1, 2, 3 or 4) or unstable angina pectoris (Braunwald Class 1-3, B-C) or a positive functional ischemia study (e.g., ETT, SPECT, Stress echocardiography or Cardiac CT).
7. Male or non-pregnant female patient (Note: females of child bearing potential must have a negative pregnancy test prior to enrollment in the study).

Angiographic Inclusion Criteria

1. Patient indicated for elective stenting of a single stenotic lesion in a native coronary artery.
2. Reference vessel >/= 2.5 mm and </= 4.0 mm in diameter by visual estimate.
3. Target lesion </= 24 mm in length by visual estimate (the intention should be to cover the whole lesion with one stent of adequate length).
4. Protected left main lesion with >50% stenosis.
5. Target lesion stenosis >/= 70% and < 100% by visual estimate.
6. Target lesion stenosis <70% who meet physiological criteria for revascularization (i.e. positive FFR).

General Exclusion Criteria:

1. Currently enrolled in another investigational device or drug trial that has not completed the primary endpoint or that clinically interferes with the current study endpoints.
2. Previously enrolled in another stent trial within the prior 2 years.
3. ANY planned elective surgery or percutaneous intervention within the subsequent 3 months.
4. A previous coronary interventional procedure of any kind within 30 days prior to the procedure.
5. The patient requires staged procedure of either the target or any non-target vessel within 9 months post-procedure.
6. The target lesion requires treatment with a device other than PTCA prior to stent placement (such as, but not limited to, directional coronary atherectomy, excimer laser, rotational atherectomy, etc.).
7. Previous drug eluting stent (DES) deployment anywhere in the target vessel.
8. Any previous stent placement within 15 mm (proximal or distal) of the target lesion.
9. Co-morbid condition(s) that could limit the patient's ability to participate in the trial or to comply with follow-up requirements, or impact the scientific integrity of the trial.
10. Concurrent medical condition with a life expectancy of less than 12 months.
11. Documented left ventricular ejection fraction (LVEF) < 30% within 12 months prior to enrollment.
12. Patients with diagnosis of MI within 72 hours (i.e. CK-MB must be returned to normal prior to enrollment) or suspected acute MI at time of enrollment
13. Previous brachytherapy in the target vessel.
14. History of cerebrovascular accident or transient ischemic attack in the last 6 months.
15. Leukopenia (leukocytes < 3.5 x 10(9) / liter).
16. Neutropenia (Absolute Neutrophil Count < 1000/mm3) </= 3 days prior to enrollment.
17. Thrombocytopenia (platelets < 100,000/mm3) pre-procedure.
18. Active peptic ulcer or active GI bleeding.
19. History of bleeding diathesis or coagulopathy or inability to accept blood transfusions.
20. Known hypersensitivity or contraindication to aspirin, heparin or bivalirudin, clopidogrel or ticlopidine, cobalt, nickel, L-605 Cobalt chromium alloy or sensitivity to contrast media, which cannot be adequately pre-medicated.
21. Serum creatinine level > 2.0 mg/dl within 7 days prior to index procedure.
22. Patients unable to tolerate dual anti-platelets therapy (DAPT) for one month post procedure.

Angiographic Exclusion Criteria

1. Unprotected left main coronary artery disease (obstruction greater than 50% in the left main coronary artery that is not protected by at least one non-obstructed bypass graft to the LAD or Circumflex artery or a branch thereof).
2. Target vessel with any lesions with greater than 50% diameter stenosis outside of a range of 5 mm proximal and distal to the target lesion based on visual estimate or on-line QCA.
3. Target lesion (or vessel) exhibiting an intraluminal thrombus (occupying > 50% of the true lumen diameter) at any time.
4. Lesion location that is aorto-ostial or within 5 mm of the origin of the left anterior descending (LAD) or left circumflex (LCX).
5. Target lesion with side branches > 2.0mm in diameter.
6. Target vessel is excessively tortuous (two bends > 90˚ to reach the target lesion).
7. Target lesion is severely calcified.
8. TIMI flow 0 or 1
9. Target lesion is in a bypass graft