Phase 2b Study of GAM501 in the Treatment of Diabetic Ulcers of the Lower Extremities

Condition(s) targeted: Diabetic Foot

Intervention: GAM501 (Biological); Placebo (Biological); Standard of care (Other)

Phase: Phase 2

Status: Recruiting

Sponsored by: Tissue Repair Company

Official(s) and/or principal investigator(s):
Jeff Kittrelle, MD, Study Chair, Affiliation: Tissue Repair Company, 6740 Top Gun St, San Diego, CA 92121 USA, 858-259-4511

Overall contact:
Barbara K Sosnowski, Ph.D., Phone: 858-793-6641, Ext: 575, Email: bsosnowski@t-r-co.com

This is a Phase 2b, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of one or two applications of topically applied GAM501 (Ad5PDGF-B/Bovine Type I Collagen Gel) in subjects ≥ 18 years old with non-healing diabetic foot ulcers. Approximately 210 adult subjects with Type I or Type II diabetes mellitus will be enrolled at approximately 30 investigational sites in the United States.

Official title: A Randomized, Double-Blind, Placebo-Controlled, Single- and Double-Dose, Comparator Arm (Standard of Care), Multicenter Phase 2b Study of Topical GAM501 (Ad5PDGF-B/Bovine Type I Collagen Gel) in the Treatment of Non-Healing Diabetic Ulcers of the Lower Extremities

Study design: Treatment, Randomized, Double Blind (Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Effect of GAM501 on the incidence of complete ulcer closure

Secondary outcome:

Time to complete ulcer closure

The absolute change and percent change in ulcer area

The durability of ulcer closure

Ulcer healing trajectories will be assessed by plots of percentage of ulcer closure versus time

Safety and tolerance

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age 18 years or older

- Diagnosis of diabetes mellitus (Type I or II) requiring insulin or hypoglycemic agents

to control blood sugars.

- Cutaneous, lower extremity ulcer of the foot that is ≥1. 5 and ≤10. 0 cm² in size and

Wagner Classification Grade 1 in appearance. Note - Ulcer area must be calculated at

Screening Visit and on the Treatment Day (Day 1) using measurements obtained by tracing the ulcer perimeter after debridement to confirm patient eligibility prior to randomization.

- Documented ulcer presence for ≥6 weeks prior to signing the informed consent form

- Recently debrided ulcer (within 2 weeks from screening visit)

- Ulcer free of all necrotic soft tissue

- Affected limb transcutaneous partial pressure oxygen (TcpO2) >40mmHg; or a toe

pressure ≥40mmHg; or a Doppler waveform consistent with adequate flow in the foot (biphasic or triphasic waveforms) at screening

- Inability to perceive 10 grams pressure using a Semmes-Weinstein 5. 07 monofilament in

the peri-ulcer area

- Willing to adhere to wearing off-loading orthopedic shoe for up to 16 weeks (i. e.,

through 2 weeks after ulcer closure) starting on Day - 14 (the first day of the

screening run-in period)

- Willing to adhere to wearing customized shoes during the durability phase of the

study

- Females of child-bearing potential must have a negative serum beta human chorionic

gonadotropin hormone (ßhCG) test result from a sample obtained in the 7 days prior to Treatment Day 1 and be neither breastfeeding nor intending to become pregnant during the study

- All individuals (study patients/partners) of childbearing potential must agree to use

a method of contraception deemed acceptable by the Investigator or agree to remain abstinent throughout the study

- Be able to understand and sign an informed consent form before entering into the

study, and must be willing to comply with all study procedures

Exclusion Criteria:

- Any unstable medical condition judged by the Investigator or Medical Monitor that

would cause the study to be detrimental to the patient

- Hemoglobin Alc (HbA1c) test result of >12% documented at the Screening Visit

- Ulcers caused primarily by untreated vascular insufficiency; or ulcers with an

etiology not related to diabetes

- Ulcers on the heel

- More than three ulcers on the target lower extremity

- The ulcer to be studied is not anatomically distinct from another ulcer(s) (i. e.,

separated by <1 cm from another ulcer or would interfere with standard of care treatment of another ulcer). Only a single ulcer can be treated in this study.

- Ulcers which decrease in area by >30% during the screening 2-week run-in period

- Ulcers with underlying osteomyelitis

- Patients presenting with the clinical characteristics of cellulitis at the ulcer site

(suppurative inflammation involving particularly the subcutaneous tissue, often mild erythema, tenderness, malaise, chills and fever)

- If either beta hemolytic streptococci (in any amount) or total bacterial load of >1e6

CFU/gram of tissue is present in the screening biopsy sample at the ulcer site, the patient should be given a single 7-day course of topical antibiotics and then redebrided and biopsied for quantitative culture. A second biopsy exceeding the limits above will result in exclusion from the study due to the high risk of local infection than may adversely affect ulcer closure.

- Revascularization surgery on the leg with the wound to be treated ≤8 weeks prior to

signing the informed consent form

- Surgery to lengthen Achilles tendon on the leg with the wound to be treated ≤8 weeks

prior to signing the informed consent form

- Necrosis, purulence, or sinus tracts that cannot be removed by debridement on foot to

be treated

- Needs concurrent topical antimicrobials to treat the ulcer site, or received such

therapies within 7 days prior to signing the informed consent form

- Received dermal substitute or living skin equivalent (e. g., Dermagraft® or Appligraf®)

within 30 days prior to signing the informed consent form

- Received prior PDGF-BB (Regranex®/becaplermin) therapy within 30 days prior to signing

the informed consent form

- Has known sensitivity to products of bovine origin

- Life expectancy of less than 12 months

- Patients with a definite diagnosis of any immunodeficiency disorder

- Viral hepatitis [patient must have a negative hepatitis B surface-antigen (HBsAg) and

hepatitis C antibody (HepCAb) test results obtained within 2 weeks prior to the Treatment Day (Day 1)]

- Active, uncontrolled connective tissue disease

- Renal failure as defined by serum creatinine >2. 5 mg/dL

- Liver function studies (e. g., AST, ALT) that are >2. 0 times upper limit of normal

- Poor nutritional status as measured by serum albumin <3. 0 g/dL

- Active cancer or a history of cancer in the 5 years prior to signing the informed

consent form (however, history of basal cell carcinoma is allowed)

- Active (i. e., recent onset of erythema, edema, and increased temperature of the foot

with normal radiographs ) Charcot or other structural deformity that would prevent adequate off-loading of the study foot

- Treatment with any systemic corticosteroid, immunosuppressive chemotherapeutic agent,

antiviral, or previous/current radiation therapy to lower extremity within 30 days prior to signing the informed consent form

- Received another investigational drug or biologic within 30 days prior to signing the

informed consent form or currently participating in an investigational drug or biologic study

- A psychiatric condition or chronic alcohol or drug abuse problem, determined from the

patient's medical history, which in the Investigator's opinion may pose a threat to patient compliance

- History of non-compliance with treatment or clinical visit attendance (i. e., this

study requires that patients will comply with the protocol and ulcer care regimen)

Barbara K Sosnowski, Ph.D., Phone: 858-793-6641, Ext: 575, Email: bsosnowski@t-r-co.com

Baptist Medical Center South, Montgomery, Alabama 36111, United States; Recruiting
Ruth Russell, Phone: 334-286-3444, Email: russ1620@bellsouth.net
Terry Treadwell, MD, Principal Investigator

Aung Foothealth Clinics, Tuscon, Arizona 85710, United States; Active, not recruiting

Banner Baywood Medical Center, Mesa, Arizona 85206, United States; Recruiting
Barbara Lambeth, RN, Email: barbara.lambeth@bannerhealth.com
Mark Starling, MD, Principal Investigator

Associated Foot & Ankle Specialists, Phoenix, Arizona 85015, United States; Recruiting
Norma Ramos, Email: norma.ramos@qwestoffice.net
Arthur Tallis, DPM, Principal Investigator

LAC-USC Medical Center, Los Angeles, California 90033, United States; Active, not recruiting

Dr. Roy Kroeker DPM, Fresno, California 93710, United States; Recruiting
Mary Kroeker, Email: mem-k@pacbell.net
Roy Kroeker, DPM, Principal Investigator

Long Beach VA Health Care System, Long Beach, California 90822, United States; Recruiting
Kay Crosser, Phone: 562-826-8190, Email: kay.crosser@va.gov
Reza Azadegan, Phone: 562 826 8000, Ext: 2887, Email: reza.azadegan@va.gov
Ian Gordon, MD, Principal Investigator

Foot Doctors of Watsonville, Watsonville, California 95076, United States; Recruiting
Juan Gutierrez, Phone: 831-728-8844, Email: juanlg82@sbcglobal.net
David Abdoo, DPM, Principal Investigator

Absolute Foot Care, Chula Vista, California 91910, United States; Recruiting
Arlene Banares, Phone: 619-370-9520, Email: abanares4@yahoo.com
James Longobardi, DPM, Principal Investigator

Dr. Jagpreet Mukker, Fresno, California 93726, United States; Recruiting
Prabhi Mukker, Phone: 559-224-5101, Email: prabhimukker@gmail.com
Jagpreet Mukker, DPM, Principal Investigator

UCLA Medical Center Olive View, Sylmar, California 91342, United States; Recruiting
Gus Chavez, Phone: 818-364-3205, Email: gchavez@ladhs.org
Soma Wali, MD, Principal Investigator
Aksone Nouvong, DPM, Sub-Investigator

Innovative Medical Technologies, Los Angeles, California 90063, United States; Recruiting
Lorinda Corona, Phone: 323-264-6187, Email: lorindac67@gmail.com
Gabriel Halperin, DPM, Principal Investigator

North American Center for Limb Preservation, New Haven, Connecticut 06515, United States; Recruiting
Sejal Patel, Email: drsejal79@yahoo.com
Peter Blume, DPM, Principal Investigator

Providence Hospital Clinical Research Center, Washington DC, District of Columbia 20017, United States; Recruiting
Augustine Nwabueze, Phone: 202-448-4054, Email: anwabueze@provhosp.org
Ana Ibrado, MD PhD, Principal Investigator

University of Miami, Miami, Florida 33136, United States; Recruiting
Carol Kittles, Email: ckittles@med.miami.edu
Robert Kirsner, MD PhD, Principal Investigator

Bay Pines VAHCS, Bay Pines, Florida 33744, United States; Recruiting
Diane Ochs, RN, Email: diane.ochs@med.va.gov
Wyatt Payne, MN, Principal Investigator

Karr Foot Kare, Lakeland, Florida 33813, United States; Recruiting
Teneca Brunner, Phone: 863-646-5960, Email: tbrunner1008@yahoo.com
Jeffrey Karr, DPM, Principal Investigator

Johns Hopkins Bayview Medical Center, Baltimore, Maryland 21224, United States; Recruiting
Yolanda Johnson, Phone: 410-550-4724, Email: yjonso5@jhmi.edu
Brenda Hensley, Phone: 410-550-0731, Email: bhensle1@jhmi.edu
Gerlad Lazarus, MD, Principal Investigator

Boston Medical Center, Boston, Massachusetts 02118, United States; Recruiting
Joan Mulrooney, RN, BSN, Phone: 617-414-6833, Email: joan.mulrooney@bmc.org
Vickie Driver, DPM, Principal Investigator

Advanced Foot & Ankle Center, Las Vegas, Nevada 89119, United States; Recruiting
Joseph Dove, Phone: 702-696-9005, Email: dovejm@yahoo.com
Cyaandi Dove, DPM, Principal Investigator

Division of Wound Healing & Regenerative Medicine NYU School of Medicine, New York City, New York 10016, United States; Not yet recruiting
Michael Michael Golinko, MD, Phone: 212-598-6000, Email: mgolinko@gmail.com
Harold Brem, MD, Principal Investigator

University of North Carolina, Chapel Hill, North Carolina 27599, United States; Recruiting
Nicole Lemire, Email: nlemire@med.unc.edu
William Marston, MD, Principal Investigator

Warren General Hospital, Warren, Pennsylvania 16365, United States; Recruiting
Sharon McConnell, Email: smcconnell@healingwounds.com
Thomas Serena, MD, Principal Investigator

Leigh Valley Hospital, Allentown, Pennsylvania 18105, United States; Recruiting
Victoria Sabella, RN, Phone: 610-969-2038, Email: victoria.sabella@lvh.com
Scott Lipkin, DPM, Principal Investigator

Western Pennsylvania Hospital, Pittsburgh, Pennsylvania 15224, United States; Recruiting
Donna Houpt, RN, Phone: 412-688-7910, Email: dhoupt@wpahs.org
Robert Mendocino, DPM, Principal Investigator

University of Texas Medical Branch, Galveston, Texas 77555, United States; Active, not recruiting

South Texas Foot Institute, San Antonio, Texas 78224, United States; Recruiting
Diana Estrada, Phone: 210-928-3668, Email: dianaapollori@yahoo.com
Bhavesh Shah, DPM, Principal Investigator

Presbyterian Hospital of Dallas, Dallas, Texas 75231, United States; Recruiting
Mary Walraven, Phone: 214-540-1821, Email: mwalraven@wound.com
Jeff Stone, Principal Investigator

St. Joseph Medical Center, Houston, Texas 77002, United States; Recruiting
Moira Hayes, Phone: 713-301-5707, Email: moira.hayes@sbcglobal.net
Leon E Etter, MD, Principal Investigator

American Diabetes Association Web Page

MATRIX Phase 2b study website

Related publications:

Steed DL, Attinger C, Colaizzi T, Crossland M, Franz M, Harkless L, Johnson A, Moosa H, Robson M, Serena T, Sheehan P, Veves A, Wiersma-Bryant L. Guidelines for the treatment of diabetic ulcers. Wound Repair Regen. 2006 Nov-Dec;14(6):680-92. No abstract available.

Starting date: November 2007
Ending date: June 2009
Last updated: January 22, 2009