Safety and Efficacy Study of DSC127 in Treating Subjects With Diabetic Ulcers

Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial to Evaluate the Safety and Effectiveness of DSC127 in Treating Subjects With Diabetic Ulcers

The purpose of this study is to assess if the experimental drug, DSC127, is safe, how well it can be tolerated, and how different doses effect the healing of the chronic foot ulcers in diabetic subjects.

Study Overview

• Status: Completed
• Conditions: Diabetic Foot; Foot Ulcer, Diabetic
• Intervention / Treatment: Drug: NorLeu3-A(1-7) in a gel formulation

Detailed Description

This study is designed as a randomized, parallel-group, double-blind, placebo-controlled trial. After a 14-day baseline to evaluate ulcer healing to ensure DU are chronic, a 4-week active treatment followed by 8 weeks of observation and assessment of the treatment will compare the effects of two concentrations of DSC127 and placebo (n = 25 evaluable subjects per group; n=75 total evaluable subjects) to identify the optimal dose of DSC127. Sustained tissue integrity will be evaluated for all subjects during a follow-up period at study weeks 16 and 24.

Subjects will be randomized in a 1:1:1 ratio to one of the three treatment groups.

Group 1: Placebo Vehicle Control Group 2: 0.03% DSC127 in Vehicle Group 3: 0.01% DSC127 in Vehicle

The four week treatment period requires daily application of the treatment to the wound site. First application each week will be at the clinic and for the remainder of the week the patient self-administers the treatment.

If wound healing occurs during the treatment or assessment periods a final assessment visit is conducted and the integrity is assessed four and twelve weeks later (usually weeks 16 and 24 of the study).

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85723
      • Southern Arizona VA Health Care System
    • Tucson, Arizona, United States, 85724
      • Southern Arizona Limb Salvage Alliance (SALSA)
  • California
    • Castro Valley, California, United States, 94546
      • Bay Area Footcare
    • San Diego, California, United States, 92103-8896
      • University of California, San Diego
    • Sylmar, California, United States, 91342-1438
      • Olive View - UCLA Medical Center
  • Illinois
    • Jacksonville, Illinois, United States, 62650
      • Passavant Area Hospital
  • Maryland
    • Georgetown, Maryland, United States, 20007
      • Georgetown University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University School of Medicine
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Eastern Carolina Foot & Ankle Specialists
  • Pennsylvania
    • Warren, Pennsylvania, United States, 16365
      • Warren General Hospital Wound Clinic
  • Texas
    • Dallas, Texas, United States, 75224
      • Renaissance Hospital Dallas
  • Virginia
    • Roanoke, Virginia, United States, 24016
      • Professional Education and Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have at least one chronic non-healing Wagner Grade 1 or Grade 2 plantar neuropathic diabetic ulcer between 1.0-6.0 cm2 on the midfoot or forefoot, including the toes but excluding the heel.
• ABI greater than 0.7 for neuroischemic or greater than 0.8 for neuropathic DU
• TcPO2 greater than 40 mm Hg or great toe systolic pressure greater than 50 mmHg
• Type I or Type II diabetes under metabolic control
• Female subjects must have a negative pregnancy test and be willing to use acceptable method of birth control for the duration of the study

Exclusion Criteria:

• Exposure to any investigational product within the last 30 days, or have known hypersensitivity to any of the study medication components
• Chronic renal insufficiency and/or chronic liver dysfunction
• Resting blood pressure (at the time of the initial visit of the Screening Period) which exceeds 160 systolic and/or 90 diastolic mmHg on 3 consecutive readings at least 15 minutes apart
• Malignancy of any kind
• Receiving hemodialysis or CAPD
• Current history of drug abuse, and/or known to be HIV positive
• Prior radiation therapy of the foot under study
• Current use of corticosteroids (within past 8 weeks), immunosuppressants (within past 8 weeks), or use of a biologic agent to include growth factors and skin equivalents (Regranex, Apligraft, or Dermagraft) in the past 90 days
• Ulcer is deemed clinically infected and requires topical antimicrobials or agents known to affect wound healing, or the subject has been taking systemic antibiotics for more than 7 days for any reason
• Sickle-cell anemia, Raynaud's or other peripheral vascular disease
• Wagner Grade 3 or higher DU, deep abscess or infection of the joint or tendon, or gangrene or osteomyelitis
• An EKG with a marked baseline prolongation of QT/QTc interval

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Vehicle Control; control placebo vehicle gel	Drug: NorLeu3-A(1-7) in a gel formulation; Gel will be applied to the wound once daily for four weeks (treatment period). Gel will have either no active ingredient (placebo), 0.03% or 0.01% active ingredient.; Other Names: NorLeu3-Angiotensin(1-7); DSC127
Active Comparator: 0.03% DSC127; 0.03 % DSC127 in Vehicle Control	Drug: NorLeu3-A(1-7) in a gel formulation; Gel will be applied to the wound once daily for four weeks (treatment period). Gel will have either no active ingredient (placebo), 0.03% or 0.01% active ingredient.; Other Names: NorLeu3-Angiotensin(1-7); DSC127
Active Comparator: 0.01% DSC127; 0.01% DSC127 in Vehicle Control	Drug: NorLeu3-A(1-7) in a gel formulation; Gel will be applied to the wound once daily for four weeks (treatment period). Gel will have either no active ingredient (placebo), 0.03% or 0.01% active ingredient.; Other Names: NorLeu3-Angiotensin(1-7); DSC127

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Primary Efficacy Parameter Will be the Proportion of Ulcers Healed by 12 Weeks as Defined as 100 % Epithelialized With no Drainage.	Healing to occur within 12 weeks of first treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Subjects in Each Treatment Group Reporting Adverse Events.		Duration of subject's participation (24 weeks)
The Rate of Re-epithelialization of the Ulcer Site.	The overall healing rate of the ulcers, based on the percent of unhealed ulcer area re-epithelialized per week.	12 weeks
The Time to Re-epithelialization of the Ulcer Site.	Average time to complete re-epithelialization of baseline ulcer area.	24 weeks

Collaborators and Investigators

• Sponsor: US Biotest, Inc.
• Collaborators: National Institutes of Health (NIH); Integra LifeSciences Corporation
• Investigators: Study Director: Gere diZerega, MD, US Biotest, Inc.

Publications and helpful links

General Publications

• Rodgers KE, Ellefson DD, Espinoza T, Roda N, Maldonado S, Dizerega GS. Effect of NorLeu3-A(1-7) on scar formation over time after full-thickness incision injury in the rat. Wound Repair Regen. 2005 May-Jun;13(3):309-17. doi: 10.1111/j.1067-1927.2005.130314.x.
• Rodgers KE, Espinoza T, Felix J, Roda N, Maldonado S, diZerega G. Acceleration of healing, reduction of fibrotic scar, and normalization of tissue architecture by an angiotensin analogue, NorLeu3-A(1-7). Plast Reconstr Surg. 2003 Mar;111(3):1195-206. doi: 10.1097/01.PRS.0000047403.23105.66.
• Rodgers K, Xiong S, Felix J, Roda N, Espinoza T, Maldonado S, Dizerega G. Development of angiotensin (1-7) as an agent to accelerate dermal repair. Wound Repair Regen. 2001 May-Jun;9(3):238-47. doi: 10.1046/j.1524-475x.2001.00238.x.
• Rodgers KE, Roda N, Felix JE, Espinoza T, Maldonado S, diZerega G. Histological evaluation of the effects of angiotensin peptides on wound repair in diabetic mice. Exp Dermatol. 2003 Dec;12(6):784-90. doi: 10.1111/j.0906-6705.2003.00087.x.
• Balingit PP, Armstrong DG, Reyzelman AM, Bolton L, Verco SJ, Rodgers KE, Nigh KA, diZerega GS. NorLeu3-A(1-7) stimulation of diabetic foot ulcer healing: results of a randomized, parallel-group, double-blind, placebo-controlled phase 2 clinical trial. Wound Repair Regen. 2012 Jul-Aug;20(4):482-90. doi: 10.1111/j.1524-475X.2012.00804.x. Epub 2012 Jun 7.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: November 20, 2008
• First Submitted That Met QC Criteria: November 21, 2008
• First Posted (Estimate): November 24, 2008

Study Record Updates

• Last Update Posted (Estimate): September 27, 2012
• Last Update Submitted That Met QC Criteria: August 27, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Infection; Peripheral vascular disease; Diabetes mellitus; Diabetic neuropathy; Topical application; plantar foot ulcers
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer; Antihypertensive Agents; Vasodilator Agents; Angiotensin I (1-7)
• Other Study ID Numbers: DSC127-2008-01