First-in-Human Study Using the SiroMax™ Sirolimus-Coated Balloon Catheter as a Percutaneous Transluminal Coronary Angioplasty (PTCA) Balloon Catheter to Treat Subjects Who Have Coronary Artery Disease (CAD) Involving In-Stent Restenosis (ISR) or an Unstented Lesion in a Small Coronary Vessel (DNSV).

Prior treatment

• Subject with planned major surgery within 30 days following the index procedure
• History of previous target vessel perforation
• Previous PCI of target vessel within 6 months prior to the procedure
• Currently participating or planning to participate, within 24 months of the index procedure, in an investigational drug or device trial
• History of bleeding diathesis, active peptic ulcer or GI bleeding within prior 6 months or coagulopathy or will refuse blood transfusions
• Planned surgery that would cause interruption in recommended DAPT duration per current guidelines
• History of a stroke within 6 months prior to the index procedure
• Concurrent life conditions with a life expectancy of less than 24 months
• Target vessel had any previous vascular brachytherapy treatment or is planned to undergo brachytherapy at index procedure
• If single-layer ISR, any previous treatment (other than balloon angioplasty alone) of the target vessel for restenosis If double-layer ISR, any treatment (other than balloon angioplasty alone) of the double-layer ISR restenosis
• Any limus family (Zotarolimus, Everolimus, Sirolimus etc.) eluting device has been placed/used in any part of the body within 3 months prior to the index procedure including any non-target lesion treated during the index procedure
• The subject is taking or has taken within the last 3 months any limus family medication(s) for any reason
• Subject is taking strong CYP3A4 Inhibitors within 14 days before the index procedure or plans to take the strong inhibitors during the study period (Strong inhibitors include: cobicistat; ritonavir; indinavir and ritonavir; itraconazole; ketoconazole; lopinavir and ritonavir; paritaprevir and ritonavir and ombitasvir (and/or dasabuvir); posaconazole; saquinavir and ritonavir; tipranavir and ritonavir; elvitegravir and ritonavir; telithromycin; voriconazole; ceritinib; clarithromycin; idealalisib; nefazodone; nelfinavir)
• Subject is taking strong CYP3A4 Inducers within 14 days before the index procedure or plans to take the strong inducers during the study period (Strong inducers include apalutamide; carbamazepine; enzalutamide; ivosidenib; lumacaftor and ivacaftor; mitotane; phenytoin; rifampin; St. John's wort)

Other illness

• Subject with history of ST-elevation myocardial infarction (STEMI) within 30 days of the index procedure
• Extensive peripheral vascular disease that precludes safe sheath insertion
• Diffuse disease distal to target lesion with impaired runoff
• Patient is a recipient of a heart transplant
• Known hypersensitivity or contraindication to aspirin, heparin, bivalirudin, or contrast agent
• History of allergic reaction or sensitivity to sirolimus or other analogue or derivative
• Known hypersensitivity to excipients with phospholipid or related origins and Poly(lactic-co-glycolic acid) (PLGA)
• Subject with history of New York Heart Association (NYHA) class III or IV heart failure
• Unprotected left main coronary artery disease with ≥ 50% stenosis
• Target lesion is the 3rd or greater stent failure (i.e., more than two \[2\] layers of stent are present at any segment of the target lesion)

Lab values

• Platelet count \<100,000 cells/mm3 or \>700,000 cells/mm3 or a white blood cell count of \<3,000 cells/mm3
• Known renal insufficiency (e.g. serum creatinine \>2.5mg/dL, or creatinine clearance ≤30 mL/min), or subject on dialysis, or acute kidney failure confirmed by 50% increase of serum creatinine within 48 hours before procedure and/or decrease in urine output
• Left ventricular ejection fraction \< 30%

Other

• Pregnant or nursing patients
• Subject presents with NSTEMI and rising biomarkers, or ongoing chest pain or is hemodynamically unstable
• Subject with planned treatment of lesion involving aorto-ostial location
• Cardiogenic shock
• Patients with lesions requiring interventional treatment in more than two vessels
• Ostial lesion or planned future treatments
• Subject is considered not able to tolerate at least 30 seconds of coronary occlusion for the target lesion treated
• Planned PCI of any vessel within 30 days post index procedure and/or planned PCI of the target vessel within 12 months post procedure
• In Investigator's opinion, the patient is not a good candidate for the study
• Target lesion at a bifurcation Note: A target lesion near a bifurcation is allowed if only a single vessel (either main vessel or side branch) is to be treated
• Evidence of extensive thrombus or dissection in target lesion
• Chronic total occlusion (CTO) in target lesion
• \>30% residual stenosis after pre-treatment of target lesion
• Target lesion is located in the left main or within any arterial or venous graft
• Target lesion is in a side branch that is "jailed" by a main vessel stent
• \> 50% stenosis of an additional proximal lesion or clinically significant distal lesion (in a vessel \>2.0mm RVD) to the target or non-target lesion
• Target vessel is excessively tortuous, defined as more than one bend \> 90° to reach target lesion
• Exclusion Criteria (Additional for ISR arm):
• Exclusion Criteria (Additional for PK Sub-Study):
• Exclusion Criteria (Additional for DNSV arm):
• Type C lesion
• Calcified or angular target lesion which cannot be pre-dilated with high pressure balloons, scoring balloon or IVL
• In-stent restenosis

• Age ≥ 21 years
• Provided written informed consent
• If a woman of child-bearing potential, agrees to use a reliable method of contraception from the time of screening through 12 months after the index procedure
• Diagnosed with symptomatic ischemic heart disease, stable or unstable angina with signs of ischemia, silent ischemia, or a positive function test
• Eligible for percutaneous coronary intervention (PCI)
• Able to tolerate dual antiplatelet therapy with aspirin, plus either Clopidogrel, Prasugrel, or Ticagrelor
• Any non-target lesions to be treated during the index procedure have been successfully treated
• Meets the additional Inclusion criteria for the corresponding arm
• Target lesion \> 50% and \< 100% stenosed by QCA in symptomatic patients, and \> 70% and \< 100% stenosed in asymptomatic patients prior to lesion pre-treatment
• Distal TIMI grade flow of 3
• Target lesion must be ≤ 26mm length
• Successful pre-treatment of the target lesion
• Target lesion is within a native coronary artery or major branch
• Inclusion Criteria (Additional for ISR arm):
• Reference vessel diameter is ≥ 2.0 mm and ≤ 4.0 mm
• Restenosis of stented coronary artery (Includes BMS and DES). The target lesion may have been treated with no more than 2 stents
• Target lesion is within a previously placed BMS or DES and does not extend further than 5 mm beyond either the proximal or distal edge of the stent
• Confirmed stent expansion ≥ 80% of distal reference vessel diameter by angiography and there is no malposed stent struts
• Inclusion Criteria (Additional for PK Sub-Study):
• Eligible for treatment in the ISR arm with one of the ten largest device sizes
• Inclusion Criteria (Additional for DNSV arm):
• Reference vessel diameter is ≥ 2.0 mm and ≤ 2.75 mm