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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Foot Ulcer, Diabetic, Diabetic Foot

Intervention / Treatment
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* Drug: NorLeu3-A(1-7) in a gel formulation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Vehicle Control<br>control placebo vehicle gel | Drug: NorLeu3-A(1-7) in a gel formulation<br>* 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.<br>* Other names: DSC127;|
| Active Comparator: 0.03% DSC127<br>0.03 % DSC127 in Vehicle Control | Drug: NorLeu3-A(1-7) in a gel formulation<br>* 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.<br>* Other names: DSC127;|
| Active Comparator: 0.01% DSC127<br>0.01% DSC127 in Vehicle Control | Drug: NorLeu3-A(1-7) in a gel formulation<br>* 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.<br>* Other names: DSC127;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes mellitus, Diabetic neuropathy, Peripheral vascular disease, Infection, Topical application, plantar foot ulcers