Clinical trial NCT02276937: Randomized Phase IIb Trial of DVC1-0101
Official title: DVC1-0101 for Intermittent Claudication Secondary to Peripheral Artery Disease: a Randomized Phase IIb Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Intermittent Claudication
Peripheral Arterial Disease
Keywords: Recombinant Sendai virus
fibroblast growth factor-2
treadmill
Lead sponsor: Kyushu University
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Labour and Welfare, Japan
name: Japan Agency for Medical Research and Development
First posted: 2014-10-28
Enrollment: 30
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Walking performance assessed by treadmill utilizing Gardner's method
timeFrame: 6 months
Secondary outcomes:
measure: NIRS measurement
timeFrame: Pre, day 14, 1, 2, 3, 4, 5, and 6 months
measure: Readministration
timeFrame: 6 months
measure: WIQ
timeFrame: Pre, 1, 3, and 6 months
measure: Clinical stage classifications
timeFrame: Pre, day 14, 1, 2, 3, 4, 5, and 6 months
measure: ABI/TBI
timeFrame: Pre, day 14, 1, 3, and 6 months
measure: VAS
timeFrame: Pre, day 1, 2, 3, 5, 7, 14 and monthly until 6 months
measure: MACE
timeFrame: Monthly until 1 year after gene transfer
Other outcomes:
Locations:
city: Matsuyama
country: Japan
facility: Matsuyama Red-Cross Hospital
state: Ehime
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Fukuoka
country: Japan
facility: Kyushu Central Hospital
city: Osaka
country: Japan
facility: Morinomiya Hospital
Study officials:
affiliation: Kyushu University
name: Yoshikazu Yonemitsu
role: STUDY_CHAIR
References:
citation: Yonemitsu Y, Matsumoto T, Itoh H, Okazaki J, Uchiyama M, Yoshida K, Onimaru M, Onohara T, Inoguchi H, Kyuragi R, Shimokawa M, Ban H, Tanaka M, Inoue M, Shu T, Hasegawa M, Nakanishi Y, Maehara Y. DVC1-0101 to treat peripheral arterial disease: a Phase I/IIa open-label dose-escalation clinical trial. Mol Ther. 2013 Mar;21(3):707-14. doi: 10.1038/mt.2012.279. Epub 2013 Jan 15.
citation: Matsumoto T, Tanaka M, Yoshiya K, Yoshiga R, Matsubara Y, Horiuchi-Yoshida K, Yonemitsu Y, Maehara Y. Improved quality of life in patients with no-option critical limb ischemia undergoing gene therapy with DVC1-0101. Sci Rep. 2016 Jul 15;6:30035. doi: 10.1038/srep30035.