Trial Outcomes & Findings for RANGER™ Paclitaxel Coated Balloon vs Standard Balloon Angioplasty (NCT NCT03064126)

A total of 440 subjects were enrolled in the trial (376 subjects in the Randomized Controlled Trial (RCT), 52 subjects in the Long Balloon (LB) substudy and 12 subjects in the Pharmacokinetic (PK) substudy). RCT subjects were randomized to Ranger Drug-Coated Balloon (DCB) or Standard Percutaneous Transluminal Angioplasty (PTA) at a 3:1 ratio, respectively. All LB and PK subjects were treated with the Ranger DCB. RCT/PK shows 60 months data; LB shows 12 month data.

History of Hyperlipidemia requiring medication rates are based on number of evaluable subjects - subjects with the data point collected.

RCT outcome measure: Primary patency of the target lesion is determined by Peak Systolic Velocity Ratio (PSVR) ≤ 2.4 (by duplex ultrasound (DUS)) and freedom from clinically-driven Target Lesion Revascularization (TLR) within 12 months from procedure. Lesion patency is defined as freedom from more than 50% stenosis based on DUS PSVR comparing data within the treated segment to the proximal normal arterial segment. PSVR \>2.4 suggests \>50% stenosis. LB Substudy outcome measure: Primary patency of the target lesion is determined by duplex ultrasound (DUS) peak systolic velocity ratio (PSVR) ≤ 2.4 in absence of clinically-driven TLR. Primary effectiveness endpoint is assessed at 6 months post-procedure. PK Substudy: There was no prespecified analysis of primary lesion patency.

RCT: MAE is defined as a composite of freedom from all-cause death through 1 month, target limb major amputation (defined as at or above the ankle) within 12 months, and/or Target Lesion Revascularization (TLR) within 12 months. LB Substudy: Primary safety endpoint assesses the occurrence of MAE defined as all-cause death through 1 month, target limb major amputation and/or TLR at 6 and 12 months post-index procedure. PK Substudy: There was no prespecified analysis of primary safety endpoint.

Technical success defined as successful delivery, balloon inflation and deflation and retrieval of the intact trial device without burst below the rated burst pressure. RCT Standard Balloon Angioplasty: Device deficiency data is only collected for Ranger DCB; data not collected for Standard PTA group; there is no pre-specified analysis of this outcome for the Standard PTA group.

Procedural success defined as residual stenosis of less than or equal to 50% (non-stented subjects) or less than or equal to 30% (stented subjects) by core laboratory evaluation.

Clinical success defined as procedural success without procedural complications including death, major target limb amputation, thrombosis of the target lesion, or clinically-driven TLR prior to discharge.

MAEs defined as all-cause of death post-index procedure (30-days), target limb major amputation, and/or target lesion revascularization (TLR) through 60-months in RCT. MAEs defined as all-cause of death post-index procedure (30-days), target limb major amputation, and/or target lesion revascularization (TLR) through 12-months in LB substudy. PK Substudy: There was no prespecified analysis of MAEs for PK substudy.

CEC adjudicated events including death of any cause, target lesion revascularization (TLR), target vessel revascularization (TVR) and target limb amputation (TLA). Denominators for the cumulative rate will be based on 1) subjects with events, and 2) subjects with no events but their follow-up time reaches (or is beyond) the earliest visit window. LB substudy follow-up through 12 month.

Endpoint determined to be a success when there is an improvement in Rutherford Classification of one or more categories as compared to pre-procedure without the need for repeat TLR. LB Substudy: Follow-up through 12-month. PK Substudy: There was no prespecified analysis of Rate of Primary Sustained Clinical Improvement for PK substudy.

Endpoint determined to be a success when there is an improvement in Rutherford Classification of one or more categories as compared to pre-procedure including those subjects with repeat TLR. LB Substudy: Follow-up through 12-months. PK Substudy: There was no prespecified analysis of Rate of Secondary Sustained Clinical Improvement for PK substudy.

Improvement of ABI by ≥ 0.1 or to an ABI ≥ 0.90 as compared to the pre-procedure value without the need for repeat revascularization. LB Substudy: Follow-up through 12-months. PK Substudy: There was no prespecified analysis of Rate of Hemodynamic Improvement for PK substudy.

The 6MWT measure the maximal walking distance that a patient achieves on a flat, hard surface within a period of 6 minutes. It evaluates the global and integrated responses of all physiological systems involved during exercise including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, neuromuscular units and muscle metabolism. Change in distance walked from baseline to 12 months. LB Substudy: There was no prespecified analysis of Walking Improvement (distance) for the LB substudy. PK Substudy: There was no prespecified analysis of Walking Improvement (distance) for PK substudy.

The WIQ is a functional assessment questionnaire that evaluates walking ability with regard to speed, distance and stair climbing ability. It also assesses the reasons that walking ability might be limited. Range of scores include 0% (worst score) to 100% (best score). Walking improvement change assessed from baseline. LB Substudy: There was no prespecified analysis of Walking Improvement for the LB substudy. PK Substudy: There was no prespecified analysis of Walking Improvement for the PK substudy.

Duplex-defined binary restenosis (PSVR \> 2.4) of the target lesion at 1, 6, 12, 24 and 36 Months (RCT) Duplex-defined binary restenosis (PSVR \> 2.4) of the target lesion at 1, 6, and 12 (LB Substudy) PK Substudy: There was no prespecified analysis of duplex defined binary restenosis of the target lesion

Patient Utility Values as assessed by change in EQ-5D from baseline at 1, 6, 12, 24 and 36-months post-procedure. The EuroQOL (EQ)-5D is a multi-attribute health classification system. The EQ-5D uses a 5-dimension (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) descriptive system, which each consisting of 5 response options (no problems, slight problems, moderate problems, severe problems, or extreme problems/inability to perform). Outcomes reported as "Improvement" defined as improving at least one category from baseline. LB Substudy: There was no prespecified analysis of Patient Utility Values for the LB Substudy. PK Substudy: There was no prespecified analysis of Patient Utility Values for the PK Substudy.

Changes in healthcare utilization over time as measured by hospitalization readmission. Readmission Rate represents (# of subjects/Total enrolled subjects) who were hospitalized due to TLR/TVR or due to Procedure/Device related AE. LB Substudy: Follow-up through 12 Month. PK Substudy: There was no prespecified analysis of healthcare utilization over time for the PK Substudy.

Summary of Pharmacokinetic Parameters in PK substudy. Paclitaxel (PTx) Dose PK parameter data not collected or analyzed in RCT or LB substudy.

Summary of Pharmacokinetic Parameters in PK substudy. cmax (ng/mL) = Maximum plasma concentration PK data not collected or analyzed in RCT or LB substudy.

Summary of Pharmacokinetic Parameters in PK substudy. - Tmax Tmax (h) = The timepoint where cmax is reached PK parameter data not collected or analyzed in RCT or LB substudy.

Summary of Pharmacokinetic Parameters in PK substudy. AUC0-t (ng\*h/mL) = Area under the blood concentration versus time curve from time zero up to the time of the last quantifiable concentration, calculated by trapezoidal methods. PK parameter data not collected or analyzed in RCT or LB substudy.