Dose Finding Study of HP802-247 in Venous Leg Ulcers

Study Overview
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Brief Summary
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This is a 16-week study for subjects with a venous leg ulcer between the knee and ankle. This research is being done to determine the effectiveness of two dosing frequencies and two different concentrations of HP802-247, together with standard care, compared to placebo, plus standard care.

Official Title
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A Phase II Randomized, Double Blind, Placebo Controlled Dose Finding Study Investigating the Efficacy of HP802-247 in Venous Leg Ulcers

Conditions
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Venous Leg Ulcer, Venous Stasis Ulcers

Intervention / Treatment
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* Biological: HP802-247
* Biological: Placebo (Vehicle)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide informed consent. Willing to comply with protocol instructions, including allowing all study assessments. Have a venous leg ulcer (venous etiology)between the knee and ankle, at or above the malleolus. Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence. Target ulcer duration greater than or equal to 6 weeks but less than or equal to 24 months. Exclusion Criteria: Women who are pregnant or lactating Therapy with another investigational agent within thirty (30) days of Screening, or during the study. A target ulcer of non-venous etiologies. Refusal of or inability to tolerate compression therapy. Therapy of the target ulcer with tissue-engineered cell-based skin equivalents within 30 days preceding the Screening Visit. Therapy of the target ulcer with topical growth factors within 1 week preceding the Screening Visit.

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 |
| --- | --- |
| Experimental: A - Low Q7D<br>Low dose HP802-247, applied at each visit | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Experimental: B - Low Q14D<br>Low dose HP802-247 applied at Visits 1, 3, 5, 7, 9, 11 and Placebo at Visits 2, 4, 6, 8, 10, and 12 | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Experimental: C - High Q7D<br>High dose HP802-247, applied at each visit | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Experimental: D - High Q14D<br>High dose HP802-247, applied at Visits 1, 3, 5, 7, 9, 11 and Placebo at Visits 2, 4, 6, 8, 10, and 12 | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Placebo Comparator: E - Vehicle<br>Placebo (Vehicle), applied at each visit | Biological: Placebo (Vehicle)<br>* Placebo (Vehicle) consisting of: Component 1 - acellular fibrinogen solution; Component 2 - acellular thrombin solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Average Percent (%) Change From Baseline in the Target Wound Area in Each Treatment Group Over the Twelve-week Double-blind Treatment Period. | For each treatment group the area of each subject's target ulcer was measured on a weekly basis, for up to 12 weeks, or until wound closure, whichever occurred first, using a laser-based wound imaging system in conjunction with software to measure area. An average of the 12 measurements were assessed. | Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan-Meier Probability of Non-Closure | This key secondary outcome was the days to wound closure based on a Kaplan-Meier survival analysis. | 14 weeks - the final visit for one subject was delayed by two weeks | 
| Percent of Change From Baseline in Target Wound Area at Each of the Twelve Double-blind Treatment Weeks. | 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. | Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first | 
| Proportion of Subjects Achieving ≥ 50% Decrease in Target Wound Area From Baseline Through Week 13 | The area of each subject's target wound was measured at each visit and the proportion of subjects with a decrease in area from baseline ≥ 50% was calculated for each treatment group. | Over the 12 week treatment period or until the wound closed, which ever occurred first. | 
| Percentage of Participants With Complete Wound Closure at Each Visit | Treatment groups were compared for the proportion of wounds closed at each weekly visit. For subjects who dropped from the study, their remaining visit values were imputed using LOCF. | Weekly, over the 12 week treatment period | 
| 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. | 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. Each weekly measurement is reported as the average of all subjects scores at each week per treatment group. | Weekly, over the 12 week treatment period | 
| Median Time to Achieve Complete Wound Closure, Based on Based on a Kaplan-Meier Survival Analysis, Over the 12-Week Treatment Period From Baseline. | This key secondary outcome was the days to wound closure based on a Kaplan-Meier survival analysis. | 14 weeks - the final visit for one subject was delayed by two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venous Leg Ulcer (VLU), Venous Stasis Ulcer (VSU), VLU, VSU, Leg Ulcer, Leg Wound