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Randomized Phase IIb Trial of DVC1-0101

Primary Purpose

Intermittent Claudication, Peripheral Arterial Disease

Status

Active

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

DVC1-0101

About this trial

This is an interventional treatment trial for Intermittent Claudication focused on measuring Recombinant Sendai virus, fibroblast growth factor-2, treadmill

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

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

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:

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.

Sites / Locations

Matsuyama Red-Cross Hospital
Kyushu University Hospital
Kyushu Central Hospital
Morinomiya Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo (0 ciu/limb)

DVC1-0101 low dose (1x10^9 ciu/limb)

DVC1-0101 high dose (5x10^9 ciu/limb)

Arm Description

Placebo control

Low dose cohort

High dose cohort

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

NIRS measurement

Measurement of oxygen dynamics in the leg muscles by near infrared spectroscopy after a treadmill

Readministration

Proportion of subjects in whom readministration was not required

WIQ

Evaluation of QOL based on the Walking Impairment Questionnaire (WIQ)

Clinical stage classifications

Time-course changes using clinical stage classifications (Fontaine classification, Rutherford classification)

ABI/TBI

Ankle-brachial pressure index/ Toe-brachial pressure index

VAS

visual analogue scale (VAS) and pain at rest evaluated by the frequency of analgesic use

MACE

Incidence of cardiovascular events (to be followed up to 5 years after administration)

Full Information

NCT ID

NCT02276937

First Posted

October 22, 2014

Last Updated

October 3, 2023

Sponsor

Kyushu University

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT02276937

Brief Title

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

October 2014 (Actual)

Primary Completion Date

December 2021 (Actual)

Study Completion Date

August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Kyushu University

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Intermittent Claudication, Peripheral Arterial Disease

Keywords

Recombinant Sendai virus, fibroblast growth factor-2, treadmill

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo (0 ciu/limb)

Arm Type

Placebo Comparator

Arm Description

Placebo control

Arm Title

DVC1-0101 low dose (1x10^9 ciu/limb)

Arm Type

Active Comparator

Arm Description

Low dose cohort

Arm Title

DVC1-0101 high dose (5x10^9 ciu/limb)

Arm Type

Active Comparator

Arm Description

High dose cohort

Intervention Type

Drug

Intervention Name(s)

DVC1-0101

Other Intervention Name(s)

rSeV/dF expressing human FGF-2 gene

Intervention Description

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.

Primary Outcome Measure Information:

Title

Walking performance assessed by treadmill utilizing Gardner's method

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

NIRS measurement

Description

Measurement of oxygen dynamics in the leg muscles by near infrared spectroscopy after a treadmill

Time Frame

Pre, day 14, 1, 2, 3, 4, 5, and 6 months

Title

Readministration

Description

Proportion of subjects in whom readministration was not required

Time Frame

6 months

Title

WIQ

Description

Evaluation of QOL based on the Walking Impairment Questionnaire (WIQ)

Time Frame

Pre, 1, 3, and 6 months

Title

Clinical stage classifications

Description

Time-course changes using clinical stage classifications (Fontaine classification, Rutherford classification)

Time Frame

Pre, day 14, 1, 2, 3, 4, 5, and 6 months

Title

ABI/TBI

Description

Ankle-brachial pressure index/ Toe-brachial pressure index

Time Frame

Pre, day 14, 1, 3, and 6 months

Title

VAS

Description

visual analogue scale (VAS) and pain at rest evaluated by the frequency of analgesic use

Time Frame

Pre, day 1, 2, 3, 5, 7, 14 and monthly until 6 months

Title

MACE

Description

Incidence of cardiovascular events (to be followed up to 5 years after administration)

Time Frame

Monthly until 1 year after gene transfer

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

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. 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 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: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yoshikazu Yonemitsu

Organizational Affiliation

Kyushu University

Official's Role

Study Chair

Facility Information:

Facility Name

Matsuyama Red-Cross Hospital

City

Matsuyama

State/Province

Ehime

Country

Japan

Facility Name

Kyushu University Hospital

City

Fukuoka

ZIP/Postal Code

812-8582

Country

Japan

Facility Name

Kyushu Central Hospital

City

Fukuoka

ZIP/Postal Code

815-8588

Country

Japan

Facility Name

Morinomiya Hospital

City

Osaka

ZIP/Postal Code

536-0025

Country

Japan

12. IPD Sharing Statement

Citations:

PubMed Identifier

23319060

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.

Results Reference

background

PubMed Identifier

27418463

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.

Results Reference

background

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Randomized Phase IIb Trial of DVC1-0101

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