Study to Evaluate the Safety and Efficacy of JVS-100 Administered to Adults With Critical Limb Ischemia

A Phase II, Randomized, Double-Blind, Placebo Controlled Dose Escalation Study to Evaluate the Safety and Efficacy of JVS-100 Administered by Direct Intramuscular Injection to Cohorts of Adults With Critical Limb Ischemia

This is a double-blind, placebo controlled study designed to evaluate the safety and efficacy of JVS-100 given to adult subjects with critical limb ischemia (CLI).

Study Overview

• Status: Completed
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Biological: JVS-100(4 mg) or placebo/8 injections; Biological: JVS-100(8 mg) or placebo/8 injections; Biological: JVS-100(8 mg) or placebo/16 injections; Biological: JVS-100(16 mg) or placebo/16 injections

Detailed Description

48 subjects diagnosed with Rutherford Class 4-5 Critical Limb Ischemia (CLI) with non-healing ulcers and/or ischemic rest pain will be enrolled in this study designed to investigate the safety and efficacy of JVS-100. JVS-100 will be delivered by direct intramuscular injection into the limbs of study subjects. Subjects will be randomized to receive a single set of direct intramuscular injections of either JVS-100 or vehicle control and will be followed for 12 months post dosing. Safety and efficacy assessments will be collected at 3 days, 4 weeks and 3, 6 and 12 months.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Haryana, India, 122001
    • Medanta-The Medicity
  • New Delhi, India, 110060
    • Sir Ganga Ram Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology PC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital/Northwestern University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • SUMMA Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women 40 years of age or older
• Rutherford Category 4 or 5
• Ankle systolic pressure of 70mmHg or less, or toe pressure of 50mmHg or less
• Poor option for surgical revascularization by open or endovascular strategies
• Those diabetic subjects who are on optimal diabetes treatment, with HbA1c <8.5 %
• Subject should be on stable therapy for the treatment of CLI, including statin and antiplatelet therapy
• Subject must be willing to forgo treatment with hyperbaric oxygen, nerve stimulation, ot sympathectomy for treatment of CLI 10 days prior to 45 days following injection of study drug

Exclusion Criteria:

• Life expectancy of less than 1 year
• Previous major amputation of the leg to be treated or planned major amputation within the first month following enrollment
• Patent revascularization (within 6 weeks)in the leg to be treated prior to enrollment
• NYHA Class IV heart failure
• Evidence of osteomyelitis or active infection
• Subjects with Buerger's Disease
• Subjects with a history of Systemic Lupus Erythematosus (SLE) flare
• Subjects with established chronic kidney (stage 5) requiring dialysis
• Uncontrolled blood pressure
• Significant hepatic disease
• Diabetic subjects with active proliferative retinopathy
• Immunodeficient states or subjects receiving chronic immunosuppressive therapy
• Any patient with a history of cancer unless 1)the cancer was limited to curable non-melanoma skin malignancies, or 2)the cancer was removed by successful tumor resection, with or without radiation or chemotherapy, 5 years or more prior to enrollment in this study without recurrence
• Pregnant or lactating women or subjects of childbearing potential not protected by an effective method of birth control
• Men unwilling to agree to barrier contraception or limit sexual activity
• Presence of any other condition that, in the opinion of the investigator, might compromise any aspect of the trial
• Acute coronary syndrome within 3 month prior to enrollment
• Previous treatment with angiogenic growth factors or with stem cell therapy within 1 year
• Participation in another clinical trial in the last 30 days
• Clinically significant elevations in PT/PTT/INR
• Non-heel wound size >20 cm2 (excluding toe gangrene) or heel wound size >10cm2 on the index limb
• History of drug or alcohol abuse in the last year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Subjects will be randomized to receive either 4 mg of JVS-100 or placebo over 8 injections.	Biological: JVS-100(4 mg) or placebo/8 injections; 4 mg of JVS-100 or placebo delivered in 8 injections
Experimental: Cohort 2; Subjects will be randomized to receive either 8 mg of JVS-100 or placebo over 8 injections.	Biological: JVS-100(8 mg) or placebo/8 injections; 8 mg of JVS-100 or placebo delivered in 8 injections
Experimental: Cohort 3; Subjects will be randomized to receive either 8 mg of JVS-100 or placebo over 16 injections.	Biological: JVS-100(8 mg) or placebo/16 injections; 8 mg of JVS-100 or placebo delivered in 16 injections
Experimental: Cohort 4; Subjects will be randomized to receive either 16 mg of JVS-100 or placebo over 16 injections.	Biological: JVS-100(16 mg) or placebo/16 injections; 16 mg of JVS-100 or placebo delivered in 16 injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Investigate the safety and tolerability of escalating doses of JVS-100 delivered via direct intramuscular injections to subjects with CLI.	Safety assessments include tracking of AEs and SAEs and laboratory assessments	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the initial efficacy of escalating doses of JVS-100 delivered via direct intramuscular injections to subjects with CLI.	Efficacy measurements include: tracking of major/minor amputations,overall survival,Quality of Life,ulcer healing, & pressure assessments.	6 months

Collaborators and Investigators

• Sponsor: Juventas Therapeutics, Inc.
• Investigators: Principal Investigator: Melina Kibbe, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: July 14, 2011
• First Submitted That Met QC Criteria: August 4, 2011
• First Posted (Estimate): August 5, 2011

Study Record Updates

• Last Update Posted (Estimate): October 23, 2014
• Last Update Submitted That Met QC Criteria: October 22, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: PAD; PVD; peripheral vascular disease; CLI; SDF-1
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: JTCS-002