SELUTION4SFA Trial

Clinical Inclusion Criteria:

1. Subject age is ≥ 18 years or minimum legal age as required by local regulations.

2. Life expectancy >1 year in opinion of investigator.

3. Documented ischemia with Rutherford classification category 2, 3 or 4.

4. Target lesion(s) in the SFA or PPA.

5. Able to walk without the assistance of a walker.

6. Subject is willing and able to provide informed consent and comply with studyprocedures and required follow-up evaluations.

7. Female subjects only: If female, then subjects of childbearing potential must have anegative pregnancy test ≤ 7 days before the procedure and be prepared to useeffective contraception for 12 months after treatment.

Angiographic Inclusion Criteria:

1. Angiographic evidence that target lesion lies within the superficial femoral arteryand/or proximal popliteal artery (P1 and P2 only).

2. Angiographic evidence that the target lesion consists of either a de novo lesion ora non-stented restenotic lesion, or a combination of both, that meets one of thefollowing criteria: A. A stenosis of 70-99% with lesion length between ≥3cm and <20cm by visualestimation. B. A total (100%) occlusion with lesion length between ≥3cm and ≤10cm by visualestimation. C. A combination lesion (stenosis and total occlusion) must have a total lesionlength between ≥3cm and <20cm by visual estimation with an occluded segment that is ≤10cm by visual estimation. D. If multiple lesions are to be treated, then only 2 lesions may be included. Thetotal combination of lengths must be between ≥3cm and < 20cm by visual estimation,and there must be at least 5 cm of artery that is not to be treated between them.

3. Target vessel reference diameter ≥4mm and ≤7mm.

4. Patent arterial inflow (common iliac, external iliac, common femoral and profundafemoris arteries, and the proximal 2 cm of the SFA) free from significant lesion (defined as ≥50% stenosis) as confirmed on angiography. Note: Where required, inflow iliac arteries (common and external iliac arteriesonly) must be successfully treated during the index procedure. Completionangiography must confirm successful treatment of inflow disease (≤30% residualstenosis, no distal embolization, and no Grade C or greater dissection ) prior topre-dilation and randomization of the target lesion(s). Drug-eluting devices are notallowed for treatment of the occluded inflow iliac arteries.

5. Angiographic evidence of adequate distal run off (defined as ≤50% stenosis) in oneor more tibial arteries on initial angiography, and if applicable, after completionof inflow artery treatment.

Note: Treatment of outflow disease is permitted during the index procedure. Drug-eluting devices are not allowed for outflow treatment.

PK Sub-Study Inclusion Criteria:

Subjects must meet all of the main protocol inclusion criteria to participate in the PK sub-study. Subjects must also meet the following additional PK sub-study inclusion criteria:

1. Subject is willing and able to provide informed consent for the PK sub-study andcomply with the PK sub-study procedures and required follow-up evaluations.

Clinical Exclusion Criteria:

1. Other surgical or endovascular procedure in the target limb that occurred within 14days prior to index procedure or is planned for within 30 days following indexprocedure, with exception for diagnostic angiography.

2. Inability to tolerate dual antiplatelet therapy.

3. Known hypersensitivity or allergy to Sirolimus or other pharmacologic agents, suchas contrast agent, which are required for the procedure and which cannot beadequately pre-treated.

4. Stroke or MI within 3 months of enrollment.

5. Symptom onset less than 14 days prior to index procedure (acute limb ischemia).

6. Lower limb disease in the contralateral leg that requires treatment at the indexprocedure, or, that is planned within 14 days prior to the index procedure or within 30 days after the index procedure.

7. Prior vascular surgery (including bypass and endarterectomy) of abdominal aorta,iliac arteries, or arteries of the index limb.

8. Non-atherosclerotic disease of the index limb (including aneurysmal disease,vasculitis, Buerger's disease)

9. Target lesion requires treatment with alternative therapies such as thrombolysis,thrombus aspiration, cutting/scoring/contoured balloon, stenting, laser, cryoplasty,intravascular lithotripsy, brachytherapy, re-entry device).

10. Subject has target lesion(s) that require treatment via pedal site.

11. Subject has target lesion(s) that require access via upper extremity arteries.

12. Hypercoagulable state or disorder present, or coagulopathy present, includingplatelet count less than 80,000 per microliter.

13. Chronic renal insufficiency (dialysis dependent, or serum creatinine >2.5 mg/dLwithin 30 days of index procedure).

14. Systemic infection (WBC > 12,000 and febrile) or known immune compromise.

15. Breast-feeding woman.

16. Currently participating in another investigational drug or device study that has notcompleted primary endpoint follow-up.

Angiographic Exclusion Criteria:

1. Presence of a previously placed stent in the treated artery.

2. Failure to successfully cross the target lesion.

3. Residual stenosis ≥30% after pre-dilatation.

PK Sub-Study Exclusion Criteria:

1. Subjects must meet none of the main protocol exclusion criteria (Section 6.1.2 ofthe main protocol) to participate in the PK sub-study. Subjects will be excluded ifany of the following additional PK sub-study exclusion criteria are met:

2. Any limus family (Zotarolimus, Everolimus, Sirolimus etc.) eluting device has beenplaced/used in any part of the body within 3 months prior to the index procedureincluding non-target lesion(s) treated during the index procedure.

3. Planned intervention with any limus family (Zotarolimus, Everolimus, Sirolimus etc.)eluting device anywhere in the body within 6 months after the index procedure. Note:staged procedures >30 days after index procedure (Exclusion #20 and #22 of the mainprotocol) are permitted only in the main protocol, and are not permitted in this PKsub-study.

4. The subject is taking or has taken within the last 3 months any limus familymedication(s) for any reason.

5. Subjects who are taking strong CYP3A4 Inhibitors within 14 days before the indexprocedure or plan to take the strong inhibitors during the study period. Stronginhibitors include: cobicistat; ritonavir; indinavir and ritonavir; itraconazole;ketoconazole; lopinavir and ritonavir; paritaprevir and ritonavir and ombitasvir (and/or dasabuvir); posaconazole; saquinavir and ritonavir; tipranavir andritonavir; elvitegravir and ritonavir; telithromycin; voriconazole; ceritinib;clarithromycin; idealalisib; nefazodone; nelfinavir.

6. Subjects who are taking strong CYP3A4 Inducers within 14 days before the indexprocedure or plan to take the strong inducers during the study period. Stronginducers include apalutamide; carbamazepine; enzalutamide; ivosidenib; lumacaftorand ivacaftor; mitotane; phenytoin; rifampin; St. John's wort.