BRight DCB First-in-Human Study

Study Overview
=================
Brief Summary
-----------------
The primary aim of this clinical study is to assess the safety and clinical performance of the BRight drug-coated balloon (DCB) in the treatment of lower limb arteries stenosis in subjects with Peripheral Artery Disease (PAD). The primary endpoint will be Late Lumen Loss (LLL) of the target lesion at 6 months.

Official Title
-----------------
BIOTRONIK- First-in-Human Assessment of the Safety and Clinical Performance of a Sirolimus Derivative-Coated Balloon (BRight DCB) in the Treatment of Subjects With de Novo Lesions in the Superficial Femoral and Proximal Popliteal Artery (BRight First Study)

Conditions
-----------------
Peripheral Artery Disease

Intervention / Treatment
-----------------
* Device: BRight DCB


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject has provided written informed consent The subject is willing to participate in the clinical investigation and to comply with the study procedures and follow-up visits Lifestyle-limiting claudication or rest pain requiring treatment of superficial femoral (SFA) and/or proximal popliteal artery (PPA) Rutherford-Becker Clinical Category of 2, 3 or 4 Target vessel reference diameter ≥5 mm and ≤ 6 mm (by visual estimation) De novo lesion with >50% stenosis by operator visual estimate within the SFA and/or proximal popliteal arteries in a single limb. Lesion must be located ≥ 1 cm below the Common Femoral Artery (CFA) bifurcation and terminate distally at ≥ 3 cm proximal to the knee joint (radiographic joint space) Single lesion length ≤100 mm for de novo stenotic lesions, or ≤ 70 mm for occluded lesions (one long lesion or multiple serial lesions) by operator visual estimate. Note: Only 1 lesion per patient can be treated. Multiple serial lesions are allowed provided that they can be treated as a single lesion with one balloon. Successful guidewire crossing of lesion. After pre-dilatation, the target lesion is ≤ 30% residual stenosis with no flow limiting dissection and treatable with a single balloon Inflow artery is patent, free from significant lesion stenosis (>50% stenosis considered significant) as confirmed by angiography. Target limb with at least 1 patent (less than 50% stenosis) tibio-peroneal run-off vessel in the target limb confirmed at baseline. (Note: treatment of outflow disease is not permitted.) Exclusion Criteria: Females who are pregnant, lactating, or intended to become pregnant, or males intending to father children during the study Subject under current medication known to affect CYP3A4 metabolism Contraindication to dual anti-platelet therapy Subject is receiving chronic anticoagulation therapy (e.g. low molecular weight heparin, warfarin, or novel direct oral anticoagulants (N(D)OACs)). Known intolerance to study medications, Limus- like drug or contrast agents that in the opinion of the investigator could not be adequately pretreated Current participation in an investigational drug or another device study History of hemorrhagic stroke within 3 months Patients with a history of Myocardial Infarction (MI) or thrombolysis within 30 days prior-index procedure Previous or planned surgical or interventional procedure within 14 days before or 30 days after index procedure (successful treatment of the ipsilateral and contralateral iliac arteries is permitted prior to enrollment- contralateral iliac artery treatment with no drug eluting technology is allowed during the index procedure) Prior endovascular treatment of the target lesion (e.g., POBA, DCB, BMS, DES, cutting balloons, scoring balloons, cryoplasty, thrombectomy, atherectomy, brachytherapy or laser devices) Previous placement of a bypass graft proximal to the target lesion Chronic renal insufficiency (eGFR < 30 mL/min within 72 hours prior to index procedure) No normal proximal arterial segment in which duplex ultrasound velocity ratios could be measured. Subject is unable to walk without assistance (e.g. walker, cane). Subject is receiving immunosuppressant therapy. Subject has known or suspected active infection at the time of the index procedure. Subject has platelet count < 100,000/mm3 or > 700,000/mm3. Subject has white blood cell (WBC) count < 3,000/mm3. Subject is unable to tolerate blood transfusions because of religious beliefs or other reasons. Subject has history of gastrointestinal hemorrhage requiring a transfusion within 3 months prior to the index procedure. Life expectancy less than 12 months due to other comorbidities, that in the investigators opinion, could limit subject ability to comply with the study required follow-up visits/procedure and threaten the study scientific integrity Treatment of the contralateral limb during the same procedure or within 30 days following the study procedure (exclusive of the iliac arteries, which can be treated prior to enrollment or during the index procedure if no drug eluting technology is used) Non femoral vascular access Target lesion would require treatment with more than one balloon Known inadequate distal outflow Acute or sub-acute thrombus in the target vessel Aneurysmal target vessel Use of adjunctive therapies (i.e. laser, atherectomy, cryoplasty, scoring/cutting balloon, brachytherapy) during the study procedure in the target lesion or target vessel Presence of concentric calcification that precludes PTA pre-dilatation Significant contralateral or ipsilateral common femoral disease that requires intervention during the index procedure Persistent hemodynamically-significant stenosis following predilatation or residual stenosis of >30%, stent placement, or flow-limiting (Grade D or greater) dissection following pre-dilatation In-stent restenosis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BRight DCB<br> | Device: BRight DCB<br>* The BRight Drug-Coated Percutaneous Transluminal Angioplasty (PTA) Balloon catheter (BRight DCB) is intended for dilatation of de novo lesions in native superficial femoral or popliteal arteries with a simultaneous release of drug to the vessel wall as a secondary action to reduce occurrence of a restenosis of the treated vessel segment.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late Lumen Loss | Late Lumen Loss, as measure by quantitative vascular angiography (QVA) | 6 months post index procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device success | Successful delivery, balloon inflation/deflation and retrieval of the intact trial device | during procedure | 
| Acute technical success | Successful vascular access and completion of the endovascular procedure and immediate achievement of a final residual diameter stenosis of ≤30% of the treated lesion by core laboratory assessed QVA on the completion angiography with no bailout stenting | during procedure | 
| Acute procedural success | Technical success without the occurrence of death, major target limb amputation, thrombosis of the target lesion, or clinically-driven TLR within 72 hours of the index procedure | 72 hours post index procedure | 
| Major Adverse Event (MAE) rate | MAE is a composite of device or procedure related death within 30 days post index procedure, major index limb amputation, cd TLR | 1, 6 and 12 months post index procedure | 
| Clinically-driven Target Lesion Revascularization (cd TLR) rate | cd TLR is defined as any repeat intervention of the target lesions or surgical bypass of the target vessel performed for restenosis > 50% or other complication involving the target lesion, after documentation of recurrent clinical symptoms of the patient. | 1, 6 and 12 months post index procedure | 
| Clinically-driven Target Vessel Revascularization (cd TVR) rate | cd TVR, defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel, after documentation of recurrent clinical symptoms of the patient. | 1, 6 and 12 months post index procedure | 
| All-cause of death rate |  | 1, 6 and 12 months post index procedure | 
| Amputation (minor and major) rate | rate of amputation (minor and major) | 1, 6 and 12 months post index procedure | 
| Change in Rutherford Classification as compared to baseline | change in the Rutherford classification between baseline and follow-up | 1, 6 and 12 months post index procedure | 
| Change in resting target limb Ankle Brachial Index (ABI) as compared to baseline | change in ABI between baseline and follow-up | 1, 6 and 12 months post index procedure | 
| Target lesion Binary Restenosis | Defined as duplex ultrasound peak systolic velocity ratio (PSVR) > 2.5 (if DUS is completed) or angiographic assessment which suggests stenosis > 50% by QVA | 1, 6 and 12 months post index procedure | 
| Target lesion primary patency | Target lesion primary patency defined as duplex ultrasound peak systolic velocity ratio (PSVR) ≤ 2.5 (if DUS is completed) or angiographic assessment which suggests stenosis ≤ 50% by QVA and the absence of Clinically-driven TLR (adjudicated by a CEC) | 1, 6 and 12 months post index procedure | 
| Change in the Walking Impairment questionnaire (WIQ) as compared to baseline | change in WIQ between baseline and follow-up | 1, 6 and 12 months post index procedure | 
| Embolic event of the index limb | occurrence of embolic event as visualized on angiography | during procedure |