Safety and Efficacy Study of VM202 in the Treatment of Chronic Non-Healing Foot Ulcers

Study Description

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Brief Summary:

This study will assess the safety and efficacy of using gene therapy via intramuscular injections of the calf for patients with chronic non-healing foot ulcers.

Condition or disease	Intervention/treatment	Phase
Foot Ulcer, Diabetic	Genetic: VM202; Other: Placebo	Phase 3

Detailed Description:

A phase III, randomized, double-blind, placebo-controlled, multicenter, 7-month study designed to assess the safety and efficacy of intramuscular (IM) injections in the calf of VM202 in patients with chronic nonhealing foot ulcers. Three hundred patients will be randomized in a 2:1 ratio of VM202 or placebo injections:

• Active -VM202 + standard of care - 200 patients
• Control - Placebo (VM202 Vehicle) + standard of care - 100 patients

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	300 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	Active: VM202 + standard of care - 200 subjects Control: Placebo (VM202 vehicle) + standard of care - 100 subjects
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	A Phase III, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Asses the Safety and Efficacy of VM202 to Treat Chronic Nonhealing Foot Ulcers in Diabetic Patients With Concomitant Peripheral Arterial Disease (PAD)
Actual Study Start Date :	January 2017
Estimated Primary Completion Date :	June 2019
Estimated Study Completion Date :	December 2019

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Active; VM202 + standard of care	Genetic: VM202; gene therapy
Placebo Comparator: Control; Placebo (VM202 Vehicle) + standard of care	Other: Placebo; Standard of care plus placebo

Outcome Measures

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Primary Outcome Measures :

1. Confirmed target wound closure by the 4 month follow-up [ Time Frame: 0-4 Months ]
   The proportion of subjects with a confirmed target wound closure by the 4 month follow-up. Complete wound closure is defined as skin re-epithelialization without drainage or dressing confirmed at two consecutive study visits at least two weeks apart.

Secondary Outcome Measures :

1. Time to complete wound closure of foot ulcer [ Time Frame: Days 0 to Month 7 ]
   The time until confirmed target wound closure
2. Proportion of subjects with a confirmed target wound closure prior to or at 7 months [ Time Frame: Days 0, 60, 74, 90, 120, 210 ]
   confirmed target wound closure prior to or at 7 months
3. Percent change in wound volume [ Time Frame: at 2 months, 3 months, 4 months, and 7 months ]
   The change in the volume of the wound
4. Percent change in wound area and wound depth [ Time Frame: at 2 months, 3 months, 4 months, and 7 months ]
   the change in the wound area and wound depth
5. Proportion of subjects with formation of new ulcers on the target foot [ Time Frame: at 2 months, 3 months, 4 months, and 7 months ]
   Number of subjects with new ulcers
6. Time to the major amputations [ Time Frame: Day 0 to Month 7 ]
   how long until major amputation occurred
7. Time to the minor amputation [ Time Frame: Day 0 tp Month 7 ]
   how long until minor amputation occurred
8. Change in ankle brachial index (ABI) [ Time Frame: at 4 months, and 7 months ]
   change in ABI at 4 and 7 months
9. Change in toe brachial index (TBI) [ Time Frame: at 4 months, and 7 months ]
   Change in TBI at 4 and 7 months
10. Change in each domain score (quality of life, social life, well-being, physical symptoms and daily living) of Cardiff Wound Impact Questionnaire (CWIQ) [ Time Frame: from baseline at 4 months and 7 month ]
    change in score of each domain on the CWIQ

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Documented symptomatic PAD, with one or more of the following criteria satisfied:

  • ABI > 0.40 and ≤ 0.90 (i.e., mild to severe PAD without critical limb ischemia) in target limb
  • TBI ≤ 0.7 in the target limb
  • Toe pressure of < 55 mm Hg in the target limb
  • A history of intermittent claudication with previous related intervention in a leg
• Documented history of Type I or II diabetes with current treatment control (HbA1c of ≤ 12.0% at Screening) and currently on oral medication and / or insulin
• No significant changes anticipated in diabetes medication regimen

• At Screening, subject has one ulcer on the target foot that fulfills all of the following criteria:

  • Present for ≥ 2 weeks and ≤1 year
  • Full- thickness and not involving bone, tendon, or capsule (probing to tendon or capsule)
  • No sign of infection or osteomyelitis
  • Ulcer must be 0.5 cm2 - 6.5 cm2 as measured at Screening Visit prior to debridement

Subjects will undergo protocol-defined standardized wound care during screening (for two weeks or longer). Subjects will be considered screen failures and will not receive study injections on Day 0 (baseline) if the target ulcer does not meet all entry criteria (see above) as well as being confirmed as non-healing.

• Be capable of understanding and complying with the protocol and signing the informed consent document prior to being subjected to any study related procedures
• If female of childbearing potential, negative urine pregnancy test at screening and using acceptable method of birth control during the study.

Exclusion Criteria:

• Will require revascularization in the target leg within 3 months of randomization;
• Unhealed prior amputation;
• In the investigator's assessment, will require an amputation in the target leg within 3 months of randomization;
• Subject diagnosed with critical limb ischemia (CLI; Rutherford score ≥ 4);
• Subjects with target foot ulcer with an etiology of vasculitis, pyoderma gangrenosum, necrobiosis lipoidica, hydrostatic pressure/venous insufficiency, any neoplasms (basalioma, Kaposi's sarcoma, squamous cell carcinoma, etc.), or due to a burn;
• More than one (1) ulcer on target foot;
• The study ulcer increased by 50% or more at baseline from screening, and, in the opinion of the investigator, the increase is due to patient noncompliance with wound care instructions or due to other mitigating factors that may interfere with interpretation of study results;
• Evidence of active infection (e.g., cellulitis, osteomyelitis) or deep ulceration exposing bone or tendon in the foot planned for treatment;
• Any gangrene;
• Current fracture in the target foot;
• Target ulcer located on Charcot foot;
• Heart Failure with a New York Heart Association (NYHA) classification of III or IV;
• Body mass index (BMI) > 35 kg/m2 at Screening;
• Stroke 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 Anti-Human T-Cell Lymphotropic Virus (HTLV) at Screening;
• Active Hepatitis B or C infection as determined by Hepatitis B surface antibody (HBsAb), Hepatitis B core antibody (IgG and [immunoglobulin M] IgM; HBcAb), Hepatitis B surface antigen (HBsAg) and Hepatitis C antibodies (Anti-HCV), at Screening;
• Specific laboratory values at screening including: Hemoglobin < 8.0 g/dL, white blood cell count (WBC) < 3,000 cells per microliter, platelet count <75,000/mm3, aspartate aminotransferase (AST) and/or aspartate aminotransferase (ALT) > 3 times the upper limit of normal or any other clinically significant lab abnormality which in the opinion of the investigator should be exclusionary;
• Glomerular filtration rate (GFR) ≤ 30 mL/min/1.73 m2
• Patients with a recent history (< 5 years) of or new screening finding of malignant neoplasm except basal cell carcinoma or squamous cell carcinoma of the skin (if excised and no evidence of recurrence for at least 1 year); patients with family history of colon cancer in any first degree relative are excluded unless they have undergone a colonoscopy in the last 12 months with negative findings;
• Subjects with any comorbid conditions likely to interfere with assessment of safety or efficacy or with an estimated life expectancy of less than 1 year;
• Subjects requiring > 81 mg daily of acetylsalicylic acid. If > 81 mg are taken at screening, subjects may be enrolled if willing/able to switch to another medication for the duration of the study;
• Subjects requiring regular (daily) COX-2 inhibitor drug(s) or high dose steroids (except inhaled steroids or ocular steroids); subjects may be enrolled if willing/able to undergo medication wash-out prior to the first dosing and to refrain from taking these drugs during the study;
• Major psychiatric disorder in past 6 months;
• History of drug or alcohol abuse / dependence in the past 2 years;
• Use of an investigational drug in the past 3 months; use of an investigational biologic in the past 12 months; concurrent participation in investigational protocol or unapproved therapeutics; and
• Unable or unwilling to give informed consent.

Contacts and Locations

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Contacts

Contact: Sheila Yi		sheila@viromed.co.kr

Locations

United States, Alabama
Central Research Associates, Inc.	Not yet recruiting
Birmingham, Alabama, United States, 35205
Contact: William Whitley, Pharm D
Principal Investigator: Jeffrey Davis, MD
United States, Arizona
University of Arizona	Not yet recruiting
Tucson, Arizona, United States, 85724
Contact: Marcy Watchman marcywatch@gmail.com
Principal Investigator: Eric Espensen, DPM
United States, Arkansas
NEA Baptist	Not yet recruiting
Jonesboro, Arkansas, United States, 72401
Principal Investigator: Christopher Rowlett, DPM
United States, California
Center for Clinical Research Inc.	Recruiting
Carmichael, California, United States, 95608
Contact: Irena Andreychenko Irena@ccr-trials.com
Principal Investigator: Gregory Tovmassian, DPM
Center for Clinical Research Inc.	Recruiting
Castro Valley, California, United States, 94546
Contact: Diana Gayana Sarkisova gayana@ccr-trials.com
Principal Investigator: Mher Vartivarian, DPM
Foot and Ankle Clinic	Recruiting
Los Angeles, California, United States, 90057
Contact: Maira Machado Maira@lafootpain.com
Principal Investigator: Felix Sigal, DPM
Center for Clinical Research Inc.	Recruiting
San Francisco, California, United States, 94115
Contact: Shelby McCray Shelby@ccr-trials.com
Principal Investigator: Alexander Reyzelman, DPM
Olive View-UCLA Education & Research Institute	Not yet recruiting
Sylmar, California, United States, 91342
Contact: Brooke Benavides bbenavides@dhs.lacounty.gov
Principal Investigator: Aksone Nouvong, DPM
United States, Florida
LCC Medical Research Institute	Recruiting
Miami, Florida, United States, 33126
Contact: Julio Lopez, MD jlopezcrc@lccmedicalresearch.com
Contact: Olivia Falcon Valdes ofalconcrc@lccmedicalresearch.com
Principal Investigator: Jacob Silverstone, DPM
Miami Dade Medical Research Institute, LLC	Recruiting
Miami, Florida, United States, 33176
Contact: Athens Sanchez asanchez@miamimedresearch.com
Principal Investigator: Francisco Oliva, DPM
United States, Illinois
Northwestern University	Recruiting
Chicago, Illinois, United States, 60611
Contact: Jing Liu, MD jing.liu@nm.org
Principal Investigator: Robert Galiano, MD
United States, Massachusetts
UMASS Memorial Med Center	Not yet recruiting
Worcester, Massachusetts, United States, 01655
Contact: Shauneen Valliere, NP shauneen.valliere@umassmed.edu
Principal Investigator: Edward Arous, MD
United States, Missouri
Saint Louis University	Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Kathryn Lindsay lindsayk@slu.edu
Principal Investigator: Catherine Wittgen, MD
United States, Pennsylvania
Martin Foot and Ankle	Recruiting
York, Pennsylvania, United States, 17402
Contact: Beth Mincer beth@martinfootandankle.com
Principal Investigator: Maria Kasper, DPM
United States, Texas
MedResearch, Inc	Not yet recruiting
El Paso, Texas, United States, 79932
Contact: Lazara Perez lperez@epmedresearch.com
Principal Investigator: Gil M Moreu, DPM
University of North Texas Health Science Center	Not yet recruiting
Fort Worth, Texas, United States, 76107
Contact: April Bell April.Bell@unthsc.edu
Principal Investigator: Travis Motley, DPM
Texas Heart Institute	Not yet recruiting
Houston, Texas, United States, 77030
Contact: Nichole Piece
Principal Investigator: Emerson Perin, MD
Centex Studies, Inc.	Recruiting
Houston, Texas, United States, 77058
Contact: Tao Delao tdelao@centexstudies.com
Principal Investigator: Joe Pouzar, MD

Sponsors and Collaborators

ViroMed Co., Ltd.

Investigators

Principal Investigator:	Emerson C. Perin, MD	Texas Heart Institute
Principal Investigator:	David G Armstrong,, DPM, MD, PhD	Southern Arizona Limb Salvage Alliance (SALSA)

More Information

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Responsible Party:	ViroMed Co., Ltd.
ClinicalTrials.gov Identifier:	NCT02563522 History of Changes
Other Study ID Numbers:	VMNHU-003
First Posted:	September 30, 2015
Last Update Posted:	October 24, 2017
Last Verified:	October 2017

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by ViroMed Co., Ltd.:

non healing ulcers; VM202; Diabetic ulcers; foot ulcers

Additional relevant MeSH terms:

Ulcer; Foot Ulcer; Peripheral Arterial Disease; Diabetic Foot; Pathologic Processes; Foot Diseases; Skin Diseases; Leg Ulcer; Skin Ulcer; Atherosclerosis	Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies