Clinical trial NCT00796744: Safety and Efficacy Study of DSC127 in Treating Subjects With Diabetic Ulcers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Foot Ulcer, Diabetic
Diabetic Foot
Keywords: Diabetes mellitus
Diabetic neuropathy
Peripheral vascular disease
Infection
Topical application
plantar foot ulcers
Lead sponsor: US Biotest, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
name: Integra LifeSciences Corporation
First posted: 2008-11-24
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: The Primary Efficacy Parameter Will be the Proportion of Ulcers Healed by 12 Weeks as Defined as 100 % Epithelialized With no Drainage.
timeFrame: Healing to occur within 12 weeks of first treatment
Secondary outcomes:
measure: The Proportion of Subjects in Each Treatment Group Reporting Adverse Events.
timeFrame: Duration of subject's participation (24 weeks)
measure: The Rate of Re-epithelialization of the Ulcer Site.
timeFrame: 12 weeks
measure: The Time to Re-epithelialization of the Ulcer Site.
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Southern Arizona VA Health Care System
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona Limb Salvage Alliance (SALSA)
state: Arizona
city: Castro Valley
country: United States
facility: Bay Area Footcare
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Sylmar
country: United States
facility: Olive View - UCLA Medical Center
state: California
city: Jacksonville
country: United States
facility: Passavant Area Hospital
state: Illinois
city: Georgetown
country: United States
facility: Georgetown University Medical Center
state: Maryland
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Greenville
country: United States
facility: Eastern Carolina Foot & Ankle Specialists
state: North Carolina
city: Warren
country: United States
facility: Warren General Hospital Wound Clinic
state: Pennsylvania
city: Dallas
country: United States
facility: Renaissance Hospital Dallas
state: Texas
city: Roanoke
country: United States
facility: Professional Education and Research Institute
state: Virginia
Study officials:
affiliation: US Biotest, Inc.
name: Gere diZerega, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.