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.

Study Overview

• Status: Active, not recruiting
• Conditions: Peripheral Arterial Disease; Intermittent Claudication
• Intervention / Treatment: Drug: DVC1-0101

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Fukuoka, Japan, 815-8588
    • Kyushu Central Hospital
  • Osaka, Japan, 536-0025
    • Morinomiya Hospital
  • Ehime
    • Matsuyama, Ehime, Japan
      • Matsuyama Red-Cross Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (0 ciu/limb); Placebo control	Drug: DVC1-0101; The investigational product will be drawn into a disposable 1 mL syringe using a 23G needle. A total of 0.5 mL of investigational product will be injected intramuscularly into each administration site. After administration, the administration sites will be wrapped with dressings.; Other Names: rSeV/dF expressing human FGF-2 gene
Active Comparator: DVC1-0101 low dose (1x10^9 ciu/limb); Low dose cohort	Drug: DVC1-0101; The investigational product will be drawn into a disposable 1 mL syringe using a 23G needle. A total of 0.5 mL of investigational product will be injected intramuscularly into each administration site. After administration, the administration sites will be wrapped with dressings.; Other Names: rSeV/dF expressing human FGF-2 gene
Active Comparator: DVC1-0101 high dose (5x10^9 ciu/limb); High dose cohort	Drug: DVC1-0101; The investigational product will be drawn into a disposable 1 mL syringe using a 23G needle. A total of 0.5 mL of investigational product will be injected intramuscularly into each administration site. After administration, the administration sites will be wrapped with dressings.; Other Names: rSeV/dF expressing human FGF-2 gene

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Walking performance assessed by treadmill utilizing Gardner's method	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	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NIRS measurement	Measurement of oxygen dynamics in the leg muscles by near infrared spectroscopy after a treadmill	Pre, day 14, 1, 2, 3, 4, 5, and 6 months
Readministration	Proportion of subjects in whom readministration was not required	6 months
WIQ	Evaluation of QOL based on the Walking Impairment Questionnaire (WIQ)	Pre, 1, 3, and 6 months
Clinical stage classifications	Time-course changes using clinical stage classifications (Fontaine classification, Rutherford classification)	Pre, day 14, 1, 2, 3, 4, 5, and 6 months
ABI/TBI	Ankle-brachial pressure index/ Toe-brachial pressure index	Pre, day 14, 1, 3, and 6 months
VAS	visual analogue scale (VAS) and pain at rest evaluated by the frequency of analgesic use	Pre, day 1, 2, 3, 5, 7, 14 and monthly until 6 months
MACE	Incidence of cardiovascular events (to be followed up to 5 years after administration)	Monthly until 1 year after gene transfer

Collaborators and Investigators

• Sponsor: Kyushu University
• Collaborators: Japan Agency for Medical Research and Development; Ministry of Health, Labour and Welfare, Japan
• Investigators: Study Chair: Yoshikazu Yonemitsu, Kyushu University

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): December 1, 2021
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: October 22, 2014
• First Submitted That Met QC Criteria: October 24, 2014
• First Posted (Estimated): October 28, 2014

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: treadmill; Recombinant Sendai virus; fibroblast growth factor-2
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases; Intermittent Claudication
• Other Study ID Numbers: CTR-001; UMIN000014926 (Registry Identifier: UMIN CTR)