Safety and Efficacy Study Using Gene Therapy for Critical Limb Ischemia

NCT01064440 | Completed Phase 2 Results DMC

• 1 other identifier: VMCLI-II-09-002/E
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 16

Brief Summary

The purpose of this study is to evaluate whether intramuscular injections of VM202 into the calf is safe and effective in the treatment of critical limb ischemia.

Conditions

Critical Limb Ischemia

Keywords

Painful legs; Ischemic legs; Treatment for Claudication; Gene therapy

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-emergent Adverse Events Following Intramuscular Administration of 8 and 16 mg Engensis (VM202) or Placebo in Subjects With Critical Limb Ischemia.

  The number of participants with treatment-emergent adverse events (TEAEs), defined as adverse events occurring after the first injection of Engensis (VM202), was assessed in moderate or high-risk Critical Limb Ischemia subjects.

  Baseline - Days 0, 14, 28, 42, 49, 90, 180, 270 and 365

• Change From Baseline in Visual Analog Scale (VAS) for Pain

  The Visual Analog Scale (VAS) for Pain scoring instrument is a 10 cm line, oriented horizontally, with the left end score of "0" indicating "no pain", and the right end score of "10" representing "pain as bad as it can be"

  Days 0, 90, 180, 270, and 365

Secondary Outcomes (10)

• Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo

  Day 0 to Days 180, 270, and 365

• Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg

  Days 0, 28, 90, 180, 270, and 365

• Change From Baseline in Perfusion of the Occluded Target Artery by Magnetic Resonance Angiogram (MRA)

  Day 0 to Days 180 and 270

• Subjects With 100% Wound Healing

  Days 0, 14, 28, 42, 49, 90, 180, 270, and 365

• Change From Baseline in the Vascular Quality of Life Total Score

  Days 0, 90, 270, and 365

Study Arms (3)

Low Dose VM202

EXPERIMENTAL

Patients in this group received 8mg total of VM202. Day 0: 4mg of VM202 (16 injections of 0.5ml of VM202) Day14: 4mg of VM202 (16 injections of 0.5ml of VM202) Day 28: 16 injections of 0.5ml of normal saline Day 42: 16 injections of 0.5ml of normal saline

Biological: Low Dose VM202; Other: Placebo

High Dose VM202

EXPERIMENTAL

Patients in this treatment group received a total of 16mg VM202. Day 0: 4mg of VM202 (16 injections of 0.5ml of VM202) Day14: 4mg of VM202 (16 injections of 0.5ml of VM202) Day 28: 4mg of VM202 (16 injections of 0.5ml of VM202) Day42: 4mg of VM202 (16 injections of 0.5ml of VM202)

Biological: High Dose VM202

Placebo

SHAM COMPARATOR

Patients in this group received a total of 8ml normal saline. Day 0: 16 injections of 0.5ml of normal saline Day 14: 16 injections of 0.5ml of normal saline Day 28: 16 injections of 0.5ml of normal saline Day 42: 16 injections of 0.5ml of normal saline

Other: Placebo

Interventions

Low Dose VM202 BIOLOGICAL

Day 0: 4mg of VM202 (16 injections of 0.5ml of VM202) Day14: 4mg of VM202 (16 injections of 0.5ml of VM202)

Also known as: DNA Plasmid, HGF-X7

Low Dose VM202

High Dose VM202 BIOLOGICAL

Day 0: 4mg of VM202 (16 injections of 0.5ml of VM202) Day 14: 4mg of VM202 (16 injections of 0.5ml of VM202) Day 28: 4mg of VM202 (16 injections of 0.5ml of VM202) Day 42: 4mg of VM202 (16 injections of 0.5ml of VM202)

Also known as: DNA Plasmid, HGF-X7

High Dose VM202

Placebo OTHER

Day 0: 16 injections of 0.5ml of normal saline Day 14: 16 injections of 0.5ml of normal saline Day 28: 16 injections of 0.5ml of normal saline Day 42: 16 injections of 0.5ml of normal saline

Also known as: Normal Saline

Low Dose VM202; Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female, between 18 and 90 years of age;
• Diagnosis of critical limb ischemia (Rutherford Class 4 or 5), including:
• A resting ankle systolic pressure (in either the dorsalis pedis or posterior tibial arteries) of ≤ 70 mmHg in the affected limb; or
• A resting toe systolic pressure of ≤ 50 mmHg in the affected limb; or
• For patients in which measurement of ankle systolic pressure is not feasible (e.g. vessel calcification and non-compressibility); TcPO2 ≤ 30 mmHg;
• Poor or suboptimal candidate for bypass graft surgery or percutaneous angioplasty;
• Pain at rest, and/or ischemic ulcers, and/or focal gangrene (\< 3 cm2) for a minimum of 2 weeks,
• Significant stenosis (≥ 75%) of one or more of the following arteries: superficial femoral, popliteal, or two or more infra-popliteal arteries as verified by angiography within 12 months prior to enrollment;
• Be willing to maintain current drug therapy for peripheral arterial disease throughout the course of the study including an anti-platelet and statin treatment unless not tolerated;
• Clinically stable on optimized medical regimen for \>30 days
• 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 urine 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 successful revascularization procedure or sympathectomy within 12 weeks prior to study entry. A clinically unsuccessful revascularization procedure is defined as one in which:
• the target vessel re-occludes (≥50%, as verified by a second angiogram. Duplex ultrasonography can be used to determine vessel patency if the patient cannot tolerate a second angiogram), or
• the target vessel remains patent, but there is no resolution of symptoms 6 weeks after the procedure (e.g. no evidence of ulcer healing, no improvement in pressures, no reduction in resting pain);
• Subjects that will require an amputation in the target leg within 4 weeks of randomization;
• Subjects with evidence of active infection (e.g., cellulitis, osteomyelitis) or deep ulceration exposing bone or tendon in the extremity planned for treatment;
• Heart Failure with a NYHA classification of III or IV;
• Stroke (NIH scale \>2) or myocardial infarction within last 3 months;
• Unstable angina
• Uncontrolled hypertension defined as sustained systolic blood pressure (SBP) \> 200 mmHg or diastolic BP (DBP) \> 110 mmHg at baseline/screening evaluation;
• Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination;
• Inflammatory disorder of the blood vessels (inflammatory angiopathy, such as Buerger's disease);
• Subjects with advanced liver disease including decompensated cirrhosis, jaundice, ascites or bleeding varices;
• Subjects currently receiving immunosuppressive medications chemotherapy, or radiation therapy;
• Positive HIV or HTLV at screening;
• Active Hepatitis B or C infection as determined by Hepatitis B surface antibody (HBsAb), Hepatitis B core antibody (IgG and IgM; HBcAb), Hepatitis B surface antigen (HBsAg) and Hepatitis C antibodies (Anti-HCV), at Screening;

Sponsors & Collaborators

• Helixmith Co., Ltd.: lead

Study Sites (16)

Cardiology PC

Birmingham, Alabama, 35211, United States

Location

Vascular and Interventional Specialist of Orange County

Orange, California, 92868, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

St. Vincent Medical Group

Indianapolis, Indiana, 46290, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55454, United States

Location

Saint Louis University

St Louis, Missouri, 63110, United States

Location

UNC School of Medicine

Chapel Hill, North Carolina, 27599, United States

Location

Jobst Vascular

Toledo, Ohio, 43506, United States

Location

University of Oklahoma HSC

Oklahoma City, Oklahoma, 73104, United States

Location

Texas Heart Institute

Houston, Texas, 77030, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Seoul National University

Seoul, Jongno-gu, 110-744, South Korea

Location

Yonsei University Health System. Severance Cardiovascular Hospital

Seoul, Seodaemun-gu, 120-752, South Korea

Location

Ewha Womans University Medical Center

Seoul, YangCheon-ku, 158-710, South Korea

Location

Related Publications (1)

• Kibbe MR, Hirsch AT, Mendelsohn FO, Davies MG, Pham H, Saucedo J, Marston W, Pyun WB, Min SK, Peterson BG, Comerota A, Choi D, Ballard J, Bartow RA, Losordo DW, Sherman W, Driver V, Perin EC. Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia. Gene Ther. 2016 Mar;23(3):306-12. doi: 10.1038/gt.2015.110. Epub 2015 Dec 8.

  PMID: 26649448 BACKGROUND

Related Links

• Plasmid DNA of HGF in patients with critical limb ischemia

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

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

jinsub.lee@helixmith.com

+82-10-8256-0439

Study Officials

• Emerson Perin, MD

  Texas Heart Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2010
• First Posted: February 8, 2010
• Study Start: July 9, 2010
• Primary Completion: August 5, 2013
• Study Completion: November 17, 2023
• Last Updated: October 6, 2025
• Results First Posted: September 19, 2024

Record last verified: 2025-08

Locations

KR (3); US (13)