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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 7
- 主要终点
- To Investigate the safety and tolerability of escalating doses of JVS-100 delivered via direct intramuscular injections to subjects with CLI.
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Cohort 1
Subjects will be randomized to receive either 4 mg of JVS-100 or placebo over 8 injections.
干预措施: JVS-100(4 mg) or placebo/8 injections (Biological)
Cohort 2
Subjects will be randomized to receive either 8 mg of JVS-100 or placebo over 8 injections.
干预措施: JVS-100(8 mg) or placebo/8 injections (Biological)
Cohort 3
Subjects will be randomized to receive either 8 mg of JVS-100 or placebo over 16 injections.
干预措施: JVS-100(8 mg) or placebo/16 injections (Biological)
Cohort 4
Subjects will be randomized to receive either 16 mg of JVS-100 or placebo over 16 injections.
干预措施: JVS-100(16 mg) or placebo/16 injections (Biological)
结局指标
主要结局
To Investigate the safety and tolerability of escalating doses of JVS-100 delivered via direct intramuscular injections to subjects with CLI.
时间窗: 12 Months
Safety assessments include tracking of AEs and SAEs and laboratory assessments
次要结局
- To investigate the initial efficacy of escalating doses of JVS-100 delivered via direct intramuscular injections to subjects with CLI.(6 months)