Randomized Phase IIb Trial of DVC1-0101

DVC1-0101 for Intermittent Claudication Secondary to Peripheral Artery Disease: a Randomized Phase IIb Trial

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.

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.

Inclusion Criteria:

1) 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.

1. arteriosclerosis obliterans with stable symptoms, have intermittent claudication (ACD < 260 m) and are able to walk on a treadmill
2. resting ankle-brachial pressure index < 0.9
3. refuse revascularization, risk of revascularization may be greater than the benefit, or develop obliteration after revascularization
4. angiographic findings show patency from the abdominal aorta through to the proximal side of the external iliac artery
5. 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

2) Administering cilostazol for at least 1 month and still meet criterion 1).

3) Aged 30 and over.

4) Either sex, either inpatients or outpatients.

5) Able to give written consent for themselves.

Exclusion Criteria:

1. Have ischemic ulcer.
2. Diagnosed with Buerger's disease.
3. Have a current or past history of life-threatening allergies.
4. Have been shown or are suspected to have cancer.
5. With concurrent proliferative intraocular neovascularization.
6. With poorly controlled diabetes mellitus.
7. With concurrent cardiac failure.
8. With untreated severe arrhythmia.
9. Have or are suspected to have interstitial pneumonia.
10. Have progressive hepatic disorders.
11. 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
12. Diagnosed with hepatic cirrhosis (classified as B or C on the Child-Pugh).
13. Have an inflammatory disease.
14. Treated with immunosuppressants or corticosteroids for the treatment of various inflammatory diseases or after organ transplantation.
15. Underwent extirpative surgery of a malignant tumor in the past 5 years.
16. Have had a cerebral hemorrhage or cerebral infarction in the past 6 months.
17. With blood diseases.
18. With moderate or severe renal dysfunction (CCr <40 mL/min)
19. With alcohol or drug dependence.
20. Pregnant/lactating female, or who wish or are suspected to be pregnant.
21. Positive HIV antibodies.
22. Took part in any other clinical studies or research in the past 30 days.
23. Have allergic to the antibiotics and/or the Ribavirin.
24. Not permitted to participate in this study by the principal investigator or sub-investigator for any other reasons.