DVC1-0101 for Intermittent Claudication Secondary to Peripheral Artery Disease: a Randomized Phase IIb Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Walking performance assessed by treadmill utilizing Gardner's method
研究概览
简要总结
DVC1-0101 is a gene therapy medicine to treat peripheral arterial disease (PAD) based on recombinant F-gene-deleted, non-transmissible Sendai virus (rSeV/dF) expressing human fibroblast growth factor-2 (FGF-2) gene.
The primary objective of the current Phase IIb study is to investigate the clinical efficacy of DVC1-0101 (1x10^9 ciu/leg, 5x10^9 ciu/leg) in patients with IC.
详细描述
DVC1-0101 is a gene therapy medicine to treat peripheral arterial disease (PAD) based on recombinant F-gene-deleted, non-transmissible Sendai virus (rSeV/dF) expressing human fibroblast growth factor-2 (FGF-2) gene. The previous Phase I/IIa study demonstrated no serious adverse event related to the administration, and suggested possible improvement of local blood flow and walking performance of PAD patients.
The primary objective of the current Phase IIb study is to investigate the clinical efficacy of DVC1-0101 (1x10^9 ciu/leg, 5x10^9 ciu/leg) in patients with IC. We also aim to examine the dose-response relationship using the rate of improvement in walking function as an indicator.
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
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet criteria (1) to (5) below and are confirmed as such by at least 1 specialist qualified by the Japanese Society for Cardiovascular Surgery and at least 1 physician with deep experience Cardiovascular Intervention.
- •arteriosclerosis obliterans with stable symptoms, have intermittent claudication (ACD < 260 m) and are able to walk on a treadmill
- •resting ankle-brachial pressure index < 0.9
- •refuse revascularization, risk of revascularization may be greater than the benefit, or develop obliteration after revascularization
- •angiographic findings show patency from the abdominal aorta through to the proximal side of the external iliac artery
- •angiographic findings meet the above criterion (4), and have stenosis or obliteration under the femoropopliteal region with morphology defined as type C or D based on TASCII
- •Administering cilostazol for at least 1 month and still meet criterion 1).
- •Aged 30 and over.
- •Either sex, either inpatients or outpatients.
- •Able to give written consent for themselves.
排除标准
- •Have ischemic ulcer.
- •Diagnosed with Buerger's disease.
- •Have a current or past history of life-threatening allergies.
- •Have been shown or are suspected to have cancer.
- •With concurrent proliferative intraocular neovascularization.
- •With poorly controlled diabetes mellitus.
- •With concurrent cardiac failure.
- •With untreated severe arrhythmia.
- •Have or are suspected to have interstitial pneumonia.
- •Have progressive hepatic disorders.
- •Have moderate or severe hepatic disorders. (1) aspartate aminotransferase or alanine aminotransferase >2.5 times the upper limit (2) Prothrombin time is 14 seconds or longer (3) Serum bilirubin >2.0 times the upper limit
- •Diagnosed with hepatic cirrhosis (classified as B or C on the Child-Pugh).
- •Have an inflammatory disease.
- •Treated with immunosuppressants or corticosteroids for the treatment of various inflammatory diseases or after organ transplantation.
- •Underwent extirpative surgery of a malignant tumor in the past 5 years.
- •Have had a cerebral hemorrhage or cerebral infarction in the past 6 months.
- •With blood diseases.
- •With moderate or severe renal dysfunction (CCr <40 mL/min)
- •With alcohol or drug dependence.
- •Pregnant/lactating female, or who wish or are suspected to be pregnant.
- •Positive HIV antibodies.
- •Took part in any other clinical studies or research in the past 30 days.
- •Have allergic to the antibiotics and/or the Ribavirin.
- •Not permitted to participate in this study by the principal investigator or sub-investigator for any other reasons.
研究组 & 干预措施
Placebo (0 ciu/limb)
Placebo control
干预措施: DVC1-0101 (Drug)
DVC1-0101 low dose (1x10^9 ciu/limb)
Low dose cohort
干预措施: DVC1-0101 (Drug)
DVC1-0101 high dose (5x10^9 ciu/limb)
High dose cohort
干预措施: DVC1-0101 (Drug)
结局指标
主要结局
Walking performance assessed by treadmill utilizing Gardner's method
时间窗: 6 months
Change rate from baseline in absolute claudication distance (%ACD) at 6 months Change of ACD from baseline at 6 months Change of peak walking time from baseline at 6 months Change of initial claudication distance (ICD) from baseline at 6 months Change of claudication onset time from baseline at 6 months
次要结局
- NIRS measurement(Pre, day 14, 1, 2, 3, 4, 5, and 6 months)
- Clinical stage classifications(Pre, day 14, 1, 2, 3, 4, 5, and 6 months)
- VAS(Pre, day 1, 2, 3, 5, 7, 14 and monthly until 6 months)
- Readministration(6 months)
- WIQ(Pre, 1, 3, and 6 months)
- ABI/TBI(Pre, day 14, 1, 3, and 6 months)
- MACE(Monthly until 1 year after gene transfer)
研究者
Yoshikazu Yonemitsu
Professor
Kyushu University