Safety and Efficacy Trial of HP802-247 in the Treatment of Chronic Venous Leg Ulcers

Study Overview
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Brief Summary
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This study is being done to find out if an investigational product called HP802-247 can help people with venous leg ulcers. Investigational means that HP802-247 has not been approved by the U.S. Food and Drug Administration (FDA). This research is being done to compare the efficacy of HP802-247 plus compression therapy against Vehicle plus compression therapy in achieving complete wound closure over the 12-week treatment period. Vehicle looks the same as HP802-247 but contains no cells. At least 440 subjects will participate. The study is going to be conducted in approximately 5 countries at approximately 50 sites across the European Union.

Detailed Description
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See Brief Summary

Official Title
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A Phase 3 Randomized Safety and Efficacy Trial of HP802-247 in the Treatment of Chronic Venous Leg Ulcers (EU)

Conditions
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Venous Ulcer, Venous Stasis Ulcer, Ulcer

Intervention / Treatment
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* Biological: HP802-247
* Other: HP802-247 Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide informed consent. Age ≥ 18 years and of either sex. Willing to comply with protocol instructions, including allowing all study assessments. Have a venous leg ulcer (VLU) between the knee and ankle (at or above the malleolus), with a surface area ≥ 2.0 cm2 and ≤ 12.0 cm2 Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence. Arterial supply adequacy confirmed Target ulcer involves a full thickness skin loss, but WITHOUT exposure of tendon, muscle, or bone. Target ulcer duration ≥ 6 weeks but ≤ 104 weeks (24 months). Acceptable state of health and nutrition Exclusion Criteria: History of anaphylaxis, serum sickness, or erythema multiforme reaction to aprotinin, bovine serum albumin or bovine serum proteins, penicillin, streptomycin, amphotericin B. Prior diagnosis of Systemic Lupus Erythematosus with elevated anti-DNA antibody titers, Buerger's disease (thromboangiitis obliterans), current diagnosis of vasculitis, or current diagnosis of claudication. Therapy with another investigational agent within thirty (30) days of Screening, or during the study. A target ulcer of non-venous etiologies (e.g., sickle cell anemia, necrobiosis lipoidica diabeticorum, pyoderma gangrenosum, vasculopathic or vasculitic). Documented history of osteomyelitis at the target wound location within 6 months preceding the Screening Visit. Refusal of or inability to tolerate compression therapy. Therapy of the target ulcer with autologous skin graft, Apligraf™, or Dermagraft™ within 30 days preceding the Screening Visit. History of cancer in the preceding 5 years (other than carcinoma in situ of the cervix or adequately treated non-melanoma skin cancers). Any prior exposure to HP802-247 or its vehicle.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HP802-247 plus compression therapy<br>HP802-247 (fibrinogen solution & thrombin solution containing living, irradiated, growth arrested keratinocytes and fibroblasts) 260 µL (130 µL, one spray, of each solution) containing 0.5 X 10(6th) cells per mL every 14 days. Subjects randomized to HP802-247 will receive Vehicle on alternate weeks. | Biological: HP802-247<br>* Study Dosage / Usage: 260 µL (130 µL, one spray, of each solution) containing 0.5 X 10(6th) cells per mL every 14 days.<br>|
| Placebo Comparator: HP802-247 Vehicle plus compression therapy<br>fibrinogen solution & thrombin solution without cells. Subjects randomized to HP802-247 Vehicle will receive Vehicle weekly. | Other: HP802-247 Vehicle<br>* HP802-247 Vehicle consists of two separate components, a fibrinogen solution (Component 1) and a cell free thrombin solution which is identical to Component 2 except that no keratinocytes and no fibroblasts are present. A single dose is created when combined on the wound surface.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the Treatment Groups for the Number of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline | For each treatment group the area of each subject's target ulcer was measured on a weekly basis, for up to 12 weeks, using a laser-based wound imaging system in conjunction with software to measure area. Following initial closure subjects returned for four weekly visits to confirm wound closure. Wounds that remained closed for four weeks were classified as confirmed closures; if a wound opened at any of the 4 visits it was not considered to have closed. For subjects who dropped from the study prior to the end of treatment, their remaining visit values were imputed using LOCF; wound status of closed was not imputed. | Weekly, over 12 Weeks or until wound closure, which ever occurred first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the Efficacy of the Treatment Groups in Achieving Complete Wound Closure, Based on Time in Days to Closure Over the 12-Week Treatment Period From Baseline. | This key secondary outcome was based on a Cox Proportional Hazard Analysis. | 12 Weeks | 
| Compare the Efficacy of the Treatment Groups in Achieving Complete Wound Closure, Based on Median Time (Days) to Closure Over the 12-Week Treatment Period From Baseline. | This key secondary outcome was based on a Kaplan-Meier Survival analysis. | 12 weeks | 
| Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | For subjects who dropped from the study, their remaining visit values were imputed using LOCF. Treatment groups were compared for percentage of participants with closed wounds at each treatment visit. | Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first | 
| Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Subjects who completed the treatment period with confirmed wound closure were followed in the post-treatment period for a further two months to determine their closed wound status (remained closed/reopened), giving a measure of persistence of wound closure following completion of treatment. | Target ulcer status observed at two (visit 1) and three (visit 2) months following initial ulcer closure. | 
| Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Target ulcer pain was measured using a Visual Analog Scale [Range: 0mm - 100mm]. Subjects marked their pain level on a 100 mm horizontal line, with a short vertical line across the scale, 0 denoting no pain and 100mm the maximum pain. | Baseline and Weekly, over the 12 week treatment period | 
| Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Target leg pain were measured using a Visual Analog Scale [Range: 0mm - 100mm]. Subjects marked their pain level on a 100 mm horizontal line, with a short vertical line across the scale, 0 denoting no pain and 100mm the maximum pain. | Baseline and Weekly, over the 12 week treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vlu, varicose veins, Venous leg ulcer, ulcer, venous stasis, compression, venous, venous stasis ulcer, wound, venous insufficiency, dvt, deep vein thrombosis