Randomized Phase IIb Trial of DVC1-0101

Sponsor

Kyushu University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02276937

Collaborator

Ministry of Health, Labour and Welfare, Japan (Other), Japan Agency for Medical Research and Development (Other)

Enrollment

Locations

Arms

Anticipated Duration (Months)

7.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Intermittent Claudication Peripheral Arterial Disease	Drug: DVC1-0101	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 1, 2014

Actual Primary Completion Date :

Nov 1, 2021

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

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

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

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

Other Names:

rSeV/dF expressing human FGF-2 gene

Outcome Measures

Primary Outcome Measures

Walking performance assessed by treadmill utilizing Gardner's method [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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Matsuyama Red-Cross Hospital	Matsuyama	Ehime	Japan
2	Kyushu University Hospital	Fukuoka		Japan	812-8582
3	Kyushu Central Hospital	Fukuoka		Japan	815-8588
4	Morinomiya Hospital	Osaka		Japan	536-0025