Advanced NanoTherapies Dual-API DCB to Treat De-Novo Lesions in Patients With Symptomatic Coronary Artery Disease

Inclusion Criteria:

1. The subject is ≥18 years and <90 years old.

2. Subject (or legal guardian) understands the trial requirements and the treatmentprocedures and provides written informed consent before any trial-specific tests orprocedures are performed.

3. Subject has been diagnosed with a symptomatic stable angina, or acute coronarysyndrome.

4. Life expectancy > 1 year.

5. The subject is planned to undergo a percutaneous coronary intervention for a knownlesion meeting the angiographic criteria set out below.

6. Women of child-bearing potential must agree to use a reliable method ofcontraception from the time of screening through 12 months after the indexprocedure. Men with a female partner of childbearing potential must agree to usecondoms plus an additional reliable contraceptive method within 12 months after theindex procedure.

7. The subject is able and willing to comply with all assessments in the study,including dual antiplatelet therapy (DAPT), ASA indefinitely, and P2Y12 inhibitorfor a minimum of 6 months for stable angina subjects, and 12 months for unstableangina and NSTEMI subjects.

8. The subject shall be under optimal medical therapy for ASCVD, which includes at aminimum high-intensity statin therapy. If statin intolerant, the subject should betreated with a PCSK9 inhibitor, ezetimibe or bempedoic acid. Angiographic Inclusion Criteria:

9. Target lesion is located within a de-novo lesion located in a native coronary arterywith a reference vessel diameter between and including 2.0 mm and 4.0mm by visualestimate, with an in-segment length <=36mm. Target lesions must have a visuallyestimated stenosis of ≥50% and be <100% in symptomatic subjects prior to lesionpre-dilation.

10. Subject has one or two lesions that meet inclusion and exclusion criteriaindividually that could be treated with a study device. If multiple lesions are treated, only two may be treated with the investigationaldevice. If two lesions are treated with the investigational device, they must be indifferent vessels. Non-target lesions (lesion to be treated with something other than theinvestigational device) may be treated at either baseline or staged PCI but never inthe same vessel as the target lesion.

11. Successful pre-dilation with semi and/or non-compliant balloon of the targetlesion(s) (defined as no major flow-limiting dissections (Grade C or higher) and <30% residual stenosis of the target lesion by a visual estimate on angiography).Adjunctive pre-dilation therapies such as scoring balloon, cutting balloon, and IVLare allowed. Rotablator or similar rotational atherectomy devices are restricted perprotocol.

Exclusion Criteria:

General Exclusion Criteria:

1. Subject has current problems with substance abuse.

2. Subject has a planned procedure that may cause non-compliance with the protocol.

3. Subject participates in another investigational drug or device clinical study thathas not reached its primary endpoint.

4. Subject intends to participate in another investigational drug or device clinicalstudy within 12 months after the index procedure.

5. Chronic total occlusion (CTO) of the target lesion(s) or Thrombolysis In MyocardialInfarction (TIMI) flow < 2.

6. Subject requires treatment of a coronary lesion(s) involving a bifurcation withsignificant ostial / proximal disease within 5mm of a side-branch greater than 2.0mm.

7. Target lesion(s) within native or synthetic vessel grafts.

8. Subject has had any major (e.g., cardiac, and non-cardiac) surgical procedure orintervention unrelated to this study within 30 days before the index procedure orhas a planned major surgical procedure or intervention within 30 days of the indexprocedure. The exception will be made in case of planned staged PCI procedures forother coronary lesions (study or non-study lesion) lesions, whereby the timeframebetween procedures shall be determined by the clinical stability of the subject asassessed by the treating investigator. The subject must re-meet the inclusioncriteria and be free from any exclusion criteria before enrolment.

9. The subject has a known coagulopathy or has a bleeding diathesis, thrombocytopenia (with platelet counts less than 100,000/microliter) or platelets > 450,000/microliter, or international normalized ratio >1.5. Subjects on chronic oralanticoagulation medications will be excluded of the study.

10. Known renal insufficiency, estimated glomerular filtration rate (eGFR) ≤30 mL/min,by institutional calculation.

11. Subject on dialysis, or acute kidney failure (as per physician judgment).

12. Subject in whom antiplatelet, anticoagulant, or thrombolytic therapy iscontraindicated or hypersensitive.

13. Subject has a known allergy to contrast agents or medications used to perform acoronary intervention that cannot be adequately pre-treated, including, but notlimited to, sirolimus, paclitaxel, aspirin, heparin, clopidogrel bisulfate,ticlopidine, prasugrel, ticagrelor.

14. Subject has a known allergy to urethane, nylon, or silicone.

15. Presentation and index admission with STEMI. An exception to this exclusion is thetreatment of the non-culprit target lesion with study device during a staged PCIprocedure which can be either during the index STEMI admission (but not at the timeof primary PCI) or electively at another date.

16. Type 2 NSTEMI

17. Presentation with ACS and ongoing chest pain and/or hemodynamic instability despitetreatment of the culprit lesion

18. History of stroke/TIA within 60 days before enrollment.

19. LVEF less than or equal to 35%.

20. Subject is confined to bed.

21. History of thrombolytic therapy within two weeks of enrollment.

22. Subject is a recipient of a heart transplant.

23. Subject is unwilling/not able to return for angiographic catheterization at 6-monthfollow-up.

24. Women who are pregnant, breast-feeding or intend to become pregnant.

25. Subject has other medical, social, or psychological problems and is unwilling orunable to comply with procedures specified in the protocol or may have difficultyreturning for follow-up visits as specified by the protocol.

26. Cardiogenic shock (SBP <80mmHg requiring inotropes, IABP, or fluid support).

27. Subject has symptomatic active COVID-19 or is asymptomatic within the past 2 weeksof a positive COVID test. Angiographic Exclusion Criteria:

28. Subject has a planned intervention in the left-main plus two separate majorepicardial territories (left-main plus 2 vessel diseases).

29. Target vessel size <2.00 mm or >4.0 mm

30. Target lesion in the left main stem.

31. Target vessel with high thrombus burden.

32. Aorto-ostial target RCA lesion (within < 10 mm of the aorta junction)

33. Moderate-severe tortuous, calcified, or angulated coronary anatomy of the targetvessel that, in the opinion of the Investigator, would result in suboptimal imagingor excessive risk of complication from placement of an IVUS catheter followingClinical Decision.

34. The lesion is located within an arterial or saphenous vein graft or distal to adiseased arterial or saphenous vein graft.

35. Target lesion is located within a previous implanted stent.