Safety Study of Gene Therapy in Treating Critical Leg Ischemia

NCT00696124 | Completed Phase 1 Results DMC

• 1 other identifier: US 06-1-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety, tolerability and preliminary efficacy of intramuscular injections of VM202 for subjects with critical limb ischemia. Subjects selected for this study will have critical limb ischemia that has not responded to standard therapy with symptoms including pain at rest and/or ischemic ulcers.

Conditions

Critical Limb Ischemia

Keywords

lower leg ischemia; peripheral artery disease

Outcome Measures

Primary Outcomes (1)

• Treatment-Emergent Adverse Events.

  Treatment-emergent adverse events defined as adverse events after the first dose of Engensis (Day 1) through Day 365

  Day 1 to Day 365

Secondary Outcomes (4)

• Change From Baseline in Pain Visual Analog Scale

  Days 15, 28, 59, 91, 180, and 365

• Change From Baseline in Ankle Brachial Index

  Days 15, 28, 59, 91, 180, and 365

• Change From Baseline in Toe Brachial Index

  Baseline and Days 1,15,28,59,91,180,and 365

• Change From Baseline in Transcutaneous Oxygen Pressure

  Days 1 to 365

Study Arms (4)

Cohort 1

EXPERIMENTAL

2 mg dose VM202. The first half of the total dose given on Day 1 and the second half on Day 15.

Biological: VM202 2 mg

Cohort 2

EXPERIMENTAL

4 mg dose VM202. The first half of the total dose given on Day 1 and the second half on Day 15.

Biological: VM202 4 mg

Cohort 3

EXPERIMENTAL

8 mg dose VM202. The first half of the total dose given on Day 1 and the second half on Day 15.

Biological: VM202 8 mg

Cohort 4

EXPERIMENTAL

16 mg dose VM202. The first half of the total dose given on Day 1 and the second half on Day 15.

Biological: VM202 16 mg

Interventions

VM202 2 mg BIOLOGICAL

2 mg intramuscular injection with the first half of the total dose given on Day 1 and the second half on Day 15

Cohort 1

VM202 4 mg BIOLOGICAL

4 mg intramuscular injection, with half of the total dose given on Day 1 and the second half given on Day 15

Cohort 2

VM202 8 mg BIOLOGICAL

8 mg intramuscular injection. The first half of the total dose given on Day 1 and the second half on Day 15.

Cohort 3

VM202 16 mg BIOLOGICAL

16 mg dose intramuscular injection. The first half of the total dose given on Day 1 and the second half on Day 15.

Cohort 4

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, between 20 and 90 years of age
• Have critical limb ischemia (Rutherford Class 4 and 5) and considered not a candidate for bypass graft surgery or percutaneous angioplasty due to co-morbid conditions, failure of previous surgical or interventional procedures or caliber of grafting arteries. Critical Limb ischemia is defined as
• Stable symptoms on standard therapy including anti-platelet agents, vascular rheologic agents, cilostazol, anticoagulant and pain medication for 30 days.
• Pain at rest and/or ischemic ulcers for a minimum of 4 weeks.
• Have diagnostic angiography of the affected limb in the last 12 months demonstrating a significant occlusion of one more of the following arteries: iliac, superficial femoral, popliteal, and one or more infra-popliteal arteries.
• Have a resting ankle systolic pressure (in either the dorsalis pedis or posterior tibial arteries) of less than or equal to 60mmHg or a resting toe systolic pressure of less than or equal to 40 mmHg in the affected limb.
• Be willing to maintain current drug therapy for peripheral arterial disease throughout the course of the study including anti-platelet and statin inhibitor treatment
• Be capable of understanding and complying with the protocol and signing the informed consent document prior to being subjected to any study related procedures
• Women who are surgically sterile or at least 1 year postmenopausal or who have been practicing adequate contraception for at least 12 weeks prior to entering the study. If the subject is of child-bearing potential, she must have a negative serum pregnancy test result prior to study enrollment and must agree to repeat pregnancy screening tests during the study
• If the subject or the subject's partner(s) is of child bearing potential, the subject and the subject's partner(s) must agree to use a "double barrier" method of birth control while participating in this study.

You may not qualify if:

• Subjects who have undergone a revascularization procedure or sympathectomy within 12 weeks prior to study entry that remains patent. A failed revascularization procedure in the previous 4 weeks is acceptable.
• Subjects with grade 3 (hemorrhages, exudates) or grade 4 (papilledema) retinopathy.
• Subjects currently receiving immunosuppressive medications, chemotherapy, radiation therapy.
• Subject with aorta-iliac occlusion (greater than 75%).
• Subjects that will require amputation within 4 weeks of randomization.
• Subjects with any co-morbid conditions likely to interfere with assessment of safety or efficacy or with an estimated life expectancy of less than 6 months
• Subjects with history of drug (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 3 months.
• Subjects with a current history or new screening finding of malignant neoplasm except for basal cell carcinoma of the skin and squamous cell carcinoma of the skin (if excised and no evidence of recurrence).
• Subjects with evidence of active infection (e.g. cellulitis, osteomyelitis) or deep ulceration exposing bone or tendon in the extremity planned for treatment.
• Hemoglobin less than 9.0 g/dL
• White Blood Cell count less than 3,000 cells/mm3
• Platelet count less than 75,000 platelets/uL
• Fasting glucose greater than 250 mg/dL
• AST and/or ALT greater than 3X upper limit of normal
• Subjects with any other condition that in the opinion of the investigator might put the subject at risk or interfere with his/her participation.

Sponsors & Collaborators

• Helixmith Co., Ltd.: lead

Study Sites (1)

Minneapolis Heart Institute Foundation/ Abbott Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Related Publications (1)

• Henry TD, Hirsch AT, Goldman J, Wang YL, Lips DL, McMillan WD, Duval S, Biggs TA, Keo HH. Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: a phase I study. Gene Ther. 2011 Aug;18(8):788-94. doi: 10.1038/gt.2011.21. Epub 2011 Mar 24.

  PMID: 21430785 BACKGROUND

Related Links

• non-viral plasmid-encoding HGF in critical limb ischemia

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia; Peripheral Arterial Disease

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Results Point of Contact

• Title: Jinsub Lee, PhD.
• Organization: Helixmith Co., Ltd.

jinsub.lee@helixmith.com

+82-10-8256-0439

Study Officials

• Timothy Henry, MD

  Minneapolis Heart Institute Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2008
• First Posted: June 12, 2008
• Study Start: April 3, 2007
• Primary Completion: October 19, 2009
• Study Completion: December 11, 2023
• Last Updated: October 6, 2025
• Results First Posted: October 18, 2024

Record last verified: 2025-08

Locations

US (1)