Temsirolimus Alone or Paired With Dexamethasone Delivered to the Adventitia to eNhance Clinical Efficacy After Femoropopliteal Revascularization

Study Overview
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Brief Summary
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This is a prospective, multi-center, pilot feasibility study to document the effects of adventitial delivery of temsirolimus or temsirolimus with dexamethasone sodium phosphate injection, USP, after revascularization of femoropopliteal lesions in symptomatic patients with moderate to severe claudication (Rutherford 2-3) or critical limb ischemia (CLI) with rest pain (Rutherford 4). Subjects will be followed for up to 60 months post index procedure.

Detailed Description
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To begin to assess the safety and effectiveness of Bullfrog Micro-Infusion Device adventitial deposition of temsirolimus or temsirolimus with dexamethasone in maintaining luminal patency and composite safety endpoints in patients with clinical evidence of moderate to severe claudication or critical limb ischemia with rest pain after revascularization of one or more angiographically significant lesion(s) in superficial femoral or popliteal arteries.

Official Title
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Temsirolimus Alone or Paired With Dexamethasone Delivered to the Adventitia to eNhance Clinical Efficacy After Femoropopliteal Revascularization

Conditions
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Peripheral Arterial Disease

Intervention / Treatment
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* Drug: Temsirolimus
* Drug: Temsirolimus and dexamethasone sodium phosphate


Participation Criteria
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Eligibility Criteria
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Inclusion Screening Criteria: Age ≥18 years and ≤85 years at study enrollment Subject has been informed of the nature of the study, agrees to participate and has signed an IRB-approved consent form Subject is ambulatory Female subjects of childbearing potential have a negative pregnancy test ≤7 days before the procedure and are willing to use a highly effective method of birth control (See Section 12.2) for one month preceding and 12 months following study treatment Subject has documented moderate to severe claudication (Rutherford 2-3) or Critical Limb Ischemia (CLI) with rest pain (Rutherford 4) in the target limb due to arterial stenosis within the superficial femoral and/or popliteal artery Life expectancy >2 years in the Investigator's opinion Angiographic Criteria (Target Lesion Definition) Target vessel reference diameter ≥3 mm and ≤8 mm Single or multiple de novo atherosclerotic or restenotic lesion(s) with ≥70% narrowing in the superficial femoral or popliteal artery meeting the following criteria: The target lesion must be ≤20 cm in total length The target lesion does not have more than 5 cm of contiguous length of intervening normal artery The target lesion does not cross into the common femoral artery or tibeoperoneal trunk The target lesion is located at least 10 mm away from any previously placed stent or graft Successful wire crossing (sub-intimal is allowed) and revascularization by balloon angioplasty of the target lesion with less than 30% residual stenosis and run-off in at least one patent vessel into the foot Exclusion Screening Criteria: Subject is already enrolled in another clinical study of systemic drug therapy or another device study that has not completed its primary endpoint Subject unwilling or unlikely to comply with visit schedule Subjects who are incapable of providing consent and/or incapable of understanding the nature, significance and implications of the clinical trial Subject is already receiving, has received in prior 2 months, or is planned in the 6 months after index procedure to receive systemic immunotherapy, chemotherapy, or systemic steroids (however, steroid pre-treatment for contrast allergy, inhaled steroids for asthma treatment or topical steroid uses are allowed) Subject is receiving chronic anticoagulation therapy e.g. warfarin (note: chronic antiplatelet therapy, e.g. aspirin and clopidigrel, and procedural anticoagulation therapy, e.g. heparin or bivalirudin, are allowed) Subject has a bilirubin level of >1.5xULN Recent (<30 days prior to study procedure) myocardial infarction Cerebrovascular accident <60 days prior to the study procedure or any history of intracerebral hemorrhage Any surgical or endovascular procedure (not including staged revascularization in the target limb, e.g. inflow revascularization prior to index procedure or below-knee revascularization after the index procedure) performed within 14 days prior to the index procedure or planned within 30 days post index procedure Planned amputation in the target limb Active foot infection or ischemic foot wound Inability to receive temsirolimus, dexamethasone or iodinated contrast medium due to labeled contra-indications or known sensitivity reactions Estimated glomerular filtration rate (eGFR, calculated from serum creatinine using an isotope dilution mass spectrometry (IDMS)-traceable equation) less than 30 mL/min Angiographic/Procedural Criteria Hemodynamically significant inflow lesion (≥50% DS) or occlusion in the ipsilateral iliac artery in which there is failure to successfully treat and obtain a <30% residual stenosis post-revascularization, with bailout stenting as needed (in-flow lesions should be treated prior to treating the target lesion) Prior stent placement in target lesion (i.e., in-stent restenosis) Target lesion restenosis of any kind within 6 months of a prior intervention Use of alternative therapy, e.g. radiation therapy, drug-eluting stents (DES) or drug-eluting balloon/drug-coated balloons (DEB/DCB) as part of the target lesion treatment during the index procedure or during the previous 12 months Use of atherectomy devices in the target lesion during the index procedure Aneurysm in the target vessel Acute thrombus in the target limb Heavy eccentric or concentric calcification at target lesion, which in the judgment of the investigator would prevent penetration of the Micro-Infusion Device needle through the vessel wall

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is an open-label study without randomization. Cohorts will be enrolled sequentially, with Group 1 followed by Group 2. Study Drug: Temsirolimus Injection (0.4 mg/mL) and 20% contrast in Group 1 or Temsirolimus Injection (0.4 mg/mL), Dexamethasone Sodium Phosphate Injection, USP (3.2 mg/mL) and 20% contrast in Group 2 Route of Administration: Bullfrog Micro-Infusion Device adventitial delivery Dosage Volume:0.5 mL per cm of target vessel length Up to 30 subjects in Group 1 and up to 30 subjects in Group 2. The study shall enroll subjects from up to 20 sites in the United States.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1 - temsirolimus injection<br>Temsirolimus Injection (0.4 mg/mL) and 20% contrast in Group 1 | Drug: Temsirolimus<br>* Temsirolimus Injection (0.4 mg/mL) and 20% contrast in Group 1<br>|
| Active Comparator: Group 2 - temsirolimus and dexamethasone injection<br>Temsirolimus Injection (0.4 mg/mL), Dexamethasone Sodium Phosphate Injection, USP (3.2 mg/mL) and 20% contrast in Group 2 | Drug: Temsirolimus and dexamethasone sodium phosphate<br>* Temsirolimus Injection (0.4 mg/mL), Dexamethasone Sodium Phosphate Injection, USP (3.2 mg/mL) and 20% contrast in Group 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Freedom from MALE-POD at 30 days | Freedom from MALE-POD at 30 days | 30 days post intervention | 
| Effectiveness - Primary patency | Primary patency (adjudicate by angio core lab) | 12 months post intervention | 
| Effectiveness - Freedom from CD-TLR | Freedom from clinically driven target lesion revascularization (CD-TLR)) at 12 months. | 12 months post intervention |