Evaluation of ABSOLVE in Diabetic Foot Ulcers

Study Overview
=================
Brief Summary
-----------------
ABSOLVE Biologic Wound Matrix is a combination of recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) and a bovine type I collagen wound dressing matrix. ABSOLVE is under development for the treatment of chronic and acute wounds. This study investigates the safety and efficacy of ABSOLVE in chronic diabetic foot ulcers (DFUs).

Detailed Description
-----------------
Patients with diabetes are at risk for developing serious health problems that may affect the feet, eyes, kidneys, skin and heart. Foot ulcerations are of great significance to the lives of millions of diabetic patients, representing one of the most common and serious complications in these patients. Up to 25% of diabetics will develop a diabetic foot ulcer (DFU) at some point in their lifetime. The prevalence of DFUs among diabetics is 4% to 10%. More than half of all foot ulcers will become infected requiring hospitalization and 1 in 5 will require amputation. Foot ulcers account for 85,000 non-trauma related lower limb amputations annually in the USA. Every 20 seconds, somewhere in the world, a limb is lost as a consequence of diabetes. Moreover, 85% of leg amputations are preceded by DFUs and more than 60% of non-traumatic lower extremity amputations (LEA) performed in the United States each year occurs secondary to complications of diabetes mellitus. After a major amputation, 50% of patients will have another limb amputated within two years. Mortality rates subsequent to amputation are alarmingly high - up to 40% at 1 year and 80% at 5 years. Patients with a history of a DFU have a 40% greater mortality rate compared to patients with diabetes alone. Improved treatments for DFUs are clearly a matter of great significance. In this study, the investigation will be focused on the safety and efficacy of ABSOLVE in treating diabetic foot ulcers.

Official Title
-----------------
A Prospective Randomized Controlled Blinded Study to Evaluate the Safety and Efficacy of rhPDGF-BB Saturated Collagen Wound Dressings on Diabetic Foot Ulcers

Conditions
-----------------
Diabetic Foot Ulcers

Intervention / Treatment
-----------------
* Drug: RhPDGF-BB
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults 30 to 75 years of age A diagnosis of Type 1 or 2 diabetes with HbAlc between 6 and 12%, an adequate blood supply defined as TcpO2 > 30 mmHg or an ankle brachial index (ABI) ≥ 0.7 on the foot with the target ulcer A DFU 2 cm2-14 cm2 that extends into the subcutaneous tissues or beyond (≤Wagner Grade 2) A DFU of at least 6 weeks duration and under care of the study investigator for at least 2 weeks following standard wound debridement with less than 30% healing Body Mass Index (BMI) of 18.5 to 40 kg/m2 Co-morbidities are under control and non-life threatening as determined by the Investigator based on medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory tests A negative pregnancy test at Screening Both males and WCBP agree to use acceptable contraceptive methods while on study Able to comprehend and sign an ICF. Exclusion Criteria: Evidence of clinically significant findings on screening evaluations (clinical, laboratory, and ECG) which, in the opinion of the Investigator would pose a safety risk or interfere with interpretation of safety data Current or recent history of significant bacterial, fungal, viral, or mycobacterial infection History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin History of myocardial infarction, congestive heart failure, or stroke History of psychotic disorder History of alcoholism or drug addiction Positive drug screen at Screening Current treatment or treatment within 30 days prior to first dose of study products with another investigational drug or current enrollment in another clinical trial Known history of HIV, hepatitis B, or hepatitis C Known hypersensitivity to any of the product's components Subjects who are unable or unlikely to comply with the protocol Pregnant or lactating.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, blinded, two-arm, clinical study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABSOLVE<br>Type I collagen sheet soaked in a solution containing rhPDGF-BB. | Drug: RhPDGF-BB<br>* One 2x4x.3cm of collagen wound matrix is saturated with 2.0 ml of the rhPDGF-BB solution.<br>* Other names: ABSOLVE;|
| Placebo Comparator: Placebo<br>Collagen sheet soaked with saline solution. | Other: Placebo<br>* Collagen Wound Dressing wetted with buffer.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | Determine safety and tolerability of ABSOLVE on patients having a poorly healing diabetic foot ulcer. | Week 0 - 24 | 
| Successful wound healing for at least two consecutive measurements. (Efficacy) | Successfully healed wound must remain closed for at least two consecutive measurements, one of which will be at the 12-week examination. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound Size | The percent change in wound size (closure) over time. | Week 0 - 24 | 
| Wound Closure | Percent incidence of complete wound closure over time. | Week 0 - 24 | 
| Complication rate | Reduction in complications. | Week 0 - 24 |