Temsirolimus Adventitial Delivery to Improve Angiographic Outcomes Below the Knee (TANGO)

NCT02908035 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: CIP0214
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 8

Brief Summary

This is a prospective, multi-center, randomized, dose escalation study to document the effects of adventitial delivery of temsirolimus (Torisel) after revascularization of lesions below the knee in symptomatic patients with critical limb ischemia (CLI).

Conditions

Chronic Limb Ischemia

Outcome Measures

Primary Outcomes (2)

• Freedom from MALE-POD

  Freedome from MALE-POD at 30 days.

  Up to 30 days post-procedure

• Transverse-view vessel area loss percentage (TVAL%) of the target lesion

  Transverse-view vessel area loss percentage (TVAL%) of the target lesion at 6 months by quantitative vascular angiography (QVA) or prior to any TLR of the target lesion before 6 months.

  Within 6 months post-procedure

Secondary Outcomes (7)

• Freedom from a composite of all-cause death, MALE and unplanned minor amputation in target limb

  Up to 30 days post-procedure

• Freedom from a composite of death, unplanned minor amputation, clinically driven TLR, and major adverse limb events (MALE)

  Up to 12 months post-procedure

• Freedom from Serious Adverse Events (SAEs)

  Up to 12 months post-procedure

• Event-free survival

  Up to 12 months post-procedure

• Improvement in % diameter stenosis and maximum late lumen loss (LLL) of the target lesion

  Up to 6 months post-procedure

Study Arms (3)

Active Comparator: Temsirolimus Delivery High Dose

ACTIVE COMPARATOR

High-Dose Group: 0.4 mg/mL temsirolimus (including 20% contrast) Patients qualifying for enrollment will be randomized 2:1 for inclusion in either the treatment (low-dose or high-dose) or the control group. The first 20 patients randomized to treatment will receive low-dose. After the first 30 patients (20 low-dose and 10 control) are enrolled in the trial, enrollment will be held until 30-day safety endpoints are met, at which point the dosage will be escalated to the high dose and the trial will resume, with the remaining 30 patients randomized 2:1 for high-dose or control.

Drug: Temsirolimus

Active Comparator: Temsirolimus Delivery Low Dose

ACTIVE COMPARATOR

Low-Dose Group: 0.1 mg/mL temsirolimus (including 20% contrast) Patients qualifying for enrollment will be randomized 2:1 for inclusion in either the treatment (low-dose or high-dose) or the control group. The first 20 patients randomized to treatment will receive low-dose. After the first 30 patients (20 low-dose and 10 control) are enrolled in the trial, enrollment will be held until 30-day safety endpoints are met, at which point the dosage will be escalated to the high dose and the trial will resume, with the remaining 30 patients randomized 2:1 for high-dose or control.

Drug: Temsirolimus

Placebo Comparator: Saline Delivery

PLACEBO COMPARATOR

Control Group: Saline/contrast (80% normal saline for injection:20% non-ionic contrast) The first 20 patients randomized to treatment will receive low-dose. After the first 30 patients (20 low-dose and 10 control) are enrolled in the trial, enrollment will be held until 30-day safety endpoints are met, at which point the dosage will be escalated to the high dose and the trial will resume, with the remaining 30 patients randomized 2:1 for high-dose or control.

Drug: Saline

Interventions

Temsirolimus DRUG

After completion of revascularization therapy and any decision to place stents, patients will be qualified for final enrollment in the study and will be treated with the investigational drug or saline. Investigators will be blinded to assignment.

Also known as: Torisel

Active Comparator: Temsirolimus Delivery High Dose; Active Comparator: Temsirolimus Delivery Low Dose

Saline DRUG

After completion of revascularization therapy and any decision to place stents, patients will be qualified for final enrollment in the study and will be treated with the investigational drug or saline. Investigators will be blinded to assignment.

Placebo Comparator: Saline Delivery

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Screening Criteria:
• Age ≥18 years and \<90 years
• Patient has been informed of the nature of the study, agrees to participate and has signed an IRB approved consent form
• Female patients 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) one month preceding and 12 months following study treatment
• Patient has documented chronic Critical Limb Ischemia (CLI) in the target limb from the distal segment (P3) of the popliteal artery to the ankle joint prior to the study procedure with Rutherford Category 3, 4 or 5
• Life expectancy \>1 year in the Investigator's opinion
• Angiographic Criteria:
• Target vessel(s) diameter ≥2 mm and ≤8 mm
• Single or multiple atherosclerotic lesion(s) ≥70% in at least one below-knee popliteal or tibial target vessel including the tibioperoneal trunk that totals up to no greater than 30 cm in length (with no greater than 5 cm length of contiguous intervening normal artery), with possible extension into the popliteal artery distal to the center of the knee joint space (the P3 segment)
• Successful revascularization of the TL with less than 30% residual stenosis, run-off down to the foot and direct in-line flow to any foot wound, if a wound is present at baseline

You may not qualify if:

• Screening Criteria
• Patient is already enrolled in another clinical study of systemic drug therapy or another device study that has not completed its primary endpoint
• Patient unwilling or unlikely to comply with visit schedule
• Patients who are incapable of providing consent and/or incapable of understanding the nature, significance and implications of the clinical trial
• Patient is already receiving or planned to receive systemic immunotherapy, chemotherapy, or steroids (however, inhaled steroids for asthma treatment or topical steroid uses are allowed)
• Patient 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
• Planned major (above the ankle) target limb amputation
• Inability to receive temsirolimus 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, except for patients with end stage renal disease on chronic hemodialysis
• Stage 3 (per SVS WIfI classification) or worse heel ulcers or heel ulcers that are determined to be primarily neuropathic in nature or non-ischemic in origin
• Angiographic/Procedural Criteria
• Hemodynamically significant inflow lesion (≥50% DS) or occlusion in the ipsilateral iliac, SFA, or popliteal arteries (P1 and P2) 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)
• Target lesion length is \>30 cm as measured from proximal normal vessel to distal normal vessel
• Total length of lesions treated during the case (including target lesion, inflow lesions, and other non-target lesions) \>30 cm

Sponsors & Collaborators

• Mercator MedSystems, Inc.: lead

Study Sites (8)

Arkansas Heart Hospital

Little Rock, Arkansas, 72211, United States

Location

St. Joseph Hospital of Orange Heart and Vascular Center

Orange, California, 92868, United States

Location

Denver Veterans Administration Hospital

Denver, Colorado, 80220, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

University Hospital

Cleveland, Ohio, 44106, United States

Location

Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Sanford Research

Sioux Falls, South Dakota, 57101, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

temsirolimus; Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2016
• First Posted: September 20, 2016
• Study Start: March 3, 2017
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2021
• Last Updated: June 11, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share

Locations

US (8)