Venous Leg Ulcers
Conditions
Keywords
Venous leg ulcer, ulcer, venous stasis, compression, venous, venous stasis ulcer, vlu
Brief summary
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.
Interventions
BIOLOGICALHP-802-247
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 106 cells per mL every 14 days.
BIOLOGICALVehicle
(fibrinogen solution & thrombin solution without cells)
Sponsors
Smith & Nephew, Inc.
Healthpoint
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare the Treatment Groups for the Proportion of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline | 12 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. 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, their remaining visit values were imputed using LOCF; wound status of closed was not imputed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first | 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. |
| Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Target ulcer status observed at two and three months following initial ulcer 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. |
| 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. | 12 Weeks | This key secondary outcome was based on a Cox Proportional Hazard Analysis and a Kaplan-Meier survival analysis. |
| Change in Target Ulcer Pain | Weekly, over 12 week treament period, baseline | Target ulcer 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. |
| Compare the Efficacy of the Treatment Groups in Achieving Complete Wound Closure, Based on the Median Time (in Days) to Closure Over the 12-Week Treatment Period From Baseline. | 12 weeks | This key secondary outcome was based on a Kaplan-Meier survival analysis. |
| Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Weekly, over the 12 week treatment period, baseline | 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. |
Countries
Canada, United States
Participant flow
Recruitment details
Subjects were screened at 43 sites in the US and 5 in Canada; between August 22, 2012 and April 18, 2014; sites included independent and hospital wound clinics and private practice sites.
Pre-assignment details
Subjects entered a 2-week run-in; subjects whose wound radius decreased by \< 0.349 cm/2weeks and met all other inclusion/exclusion (I/E) criteria were eligible for randomization. After completion of the treatment period, subjects entered a three-month follow up period.
Participants by arm
| Arm | Count |
|---|---|
| HP802-247 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 106 cells per mL every 14 days.
HP-802-247: 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 106 cells per mL every 14 days. | 211 |
| Vehicle Vehicle Control (fibrinogen solution & thrombin solution without cells)
Vehicle | 210 |
| Total | 421 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Post Treatment Follow-Up, 3 Months | Death | 1 | 5 |
| Post Treatment Follow-Up, 3 Months | Lost to Follow-up | 1 | 2 |
| Post Treatment Follow-Up, 3 Months | Site Closure | 0 | 1 |
| Post Treatment Follow-Up, 3 Months | Withdrawal by Subject | 2 | 1 |
| Treatment Period, 12 Weeks | Adverse Event | 10 | 4 |
| Treatment Period, 12 Weeks | Death | 0 | 1 |
| Treatment Period, 12 Weeks | Lost to Follow-up | 1 | 1 |
| Treatment Period, 12 Weeks | Moved out of the area | 0 | 2 |
| Treatment Period, 12 Weeks | Protocol Violation | 0 | 1 |
| Treatment Period, 12 Weeks | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | HP802-247 | Vehicle | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 75 Participants | 72 Participants | 147 Participants |
| Age, Categorical Between 18 and 65 years | 136 Participants | 138 Participants | 274 Participants |
| Age, Continuous | 60.5 years STANDARD_DEVIATION 14.8 | 61.0 years STANDARD_DEVIATION 12.5 | 60.7 years STANDARD_DEVIATION 13.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 42 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 175 Participants | 168 Participants | 343 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 43 Participants | 34 Participants | 77 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 7 Participants | 10 Participants |
| Race (NIH/OMB) White | 160 Participants | 167 Participants | 327 Participants |
| Region of Enrollment Canada | 9 participants | 13 participants | 22 participants |
| Region of Enrollment United States | 202 participants | 197 participants | 399 participants |
| Sex: Female, Male Female | 71 Participants | 82 Participants | 153 Participants |
| Sex: Female, Male Male | 140 Participants | 128 Participants | 268 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 119 / 222 | 107 / 225 |
| serious Total, serious adverse events | 17 / 222 | 21 / 225 |
Outcome results
Primary
Compare the Treatment Groups for the Proportion 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, their remaining visit values were imputed using LOCF; wound status of closed was not imputed.
Time frame: 12 Weeks
Population: ITT Populations: Subjects who received at least one dose of test article. Analysis was by the Cochrane Mantel Haenszel (CMH) test, adjusted for sites, with significance being at P \< 0.05
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HP802-247 | Compare the Treatment Groups for the Proportion of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline | Wound Closed | 129 participants |
| HP802-247 | Compare the Treatment Groups for the Proportion of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline | Wound Not Closed | 82 participants |
| Vehicle | Compare the Treatment Groups for the Proportion of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline | Wound Closed | 126 participants |
| Vehicle | Compare the Treatment Groups for the Proportion of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline | Wound Not Closed | 84 participants |
p-value: 0.5896Cochran-Mantel-Haenszel
Secondary
Change 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.
Time frame: Weekly, over the 12 week treatment period, baseline
Population: ITT Populations: Subjects who received at least one dose of test article. Data were analyzed by an ANCOVA, adjusted for site and baseline score.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 01 | -3.74 units on a scale | Standard Error 1.22 |
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 02 | -4.18 units on a scale | Standard Error 1.39 |
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 03 | -6.14 units on a scale | Standard Error 1.4 |
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 04 | -8.2 units on a scale | Standard Error 1.42 |
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 05 | -10.6 units on a scale | Standard Error 1.38 |
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 06 | -11.04 units on a scale | Standard Error 1.53 |
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 07 | -11.57 units on a scale | Standard Error 1.54 |
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 08 | -11.18 units on a scale | Standard Error 1.53 |
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 09 | -12.7 units on a scale | Standard Error 1.5 |
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 10 | -12.55 units on a scale | Standard Error 1.52 |
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 11 | -12.35 units on a scale | Standard Error 1.49 |
| HP802-247 | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 12 | -12.1 units on a scale | Standard Error 1.49 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 11 | -11.56 units on a scale | Standard Error 1.48 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 01 | -2.19 units on a scale | Standard Error 1.22 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 07 | -9.77 units on a scale | Standard Error 1.53 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 02 | -4.03 units on a scale | Standard Error 1.38 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 10 | -11.2 units on a scale | Standard Error 1.51 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 03 | -5.91 units on a scale | Standard Error 1.39 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 08 | -10.65 units on a scale | Standard Error 1.53 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 04 | -6.71 units on a scale | Standard Error 1.41 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 12 | -12.27 units on a scale | Standard Error 1.48 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 05 | -8.62 units on a scale | Standard Error 1.37 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 09 | -11.26 units on a scale | Standard Error 1.49 |
| Vehicle | Change in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 06 | -8.2 units on a scale | Standard Error 1.52 |
Comparison: Week 01p-value: 0.3601ANCOVA
Comparison: Week 02p-value: 0.9398ANCOVA
Comparison: Week 03p-value: 0.905ANCOVA
Comparison: Week 04p-value: 0.4471ANCOVA
Comparison: Week 05p-value: 0.3004ANCOVA
Comparison: Week 06p-value: 0.1815ANCOVA
Comparison: Week 07p-value: 0.399ANCOVA
Comparison: Week 08p-value: 0.8027ANCOVA
Comparison: Week 09p-value: 0.4913ANCOVA
Comparison: Week 10p-value: 0.5227ANCOVA
Comparison: Week 11p-value: 0.7032ANCOVA
p-value: 0.9366ANCOVA
Secondary
Change in Target Ulcer Pain
Target ulcer 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.
Time frame: Weekly, over 12 week treament period, baseline
Population: ITT Populations: Subjects who received at least one dose of test article. Data were analyzed by an ANCOVA, adjusted for site and baseline score.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| HP802-247 | Change in Target Ulcer Pain | Week 04 | -12.17 units on a scale | Standard Error 1.3 |
| HP802-247 | Change in Target Ulcer Pain | Week 07 | -15.8 units on a scale | Standard Error 1.38 |
| HP802-247 | Change in Target Ulcer Pain | Week 02 | -7.59 units on a scale | Standard Error 1.25 |
| HP802-247 | Change in Target Ulcer Pain | Week 08 | -16.28 units on a scale | Standard Error 1.38 |
| HP802-247 | Change in Target Ulcer Pain | Week 05 | -13.15 units on a scale | Standard Error 1.23 |
| HP802-247 | Change in Target Ulcer Pain | Week 09 | -17.16 units on a scale | Standard Error 1.32 |
| HP802-247 | Change in Target Ulcer Pain | Week 10 | -17.65 units on a scale | Standard Error 1.32 |
| HP802-247 | Change in Target Ulcer Pain | Week 03 | -10.32 units on a scale | Standard Error 1.27 |
| HP802-247 | Change in Target Ulcer Pain | Week 11 | -17.34 units on a scale | Standard Error 1.33 |
| HP802-247 | Change in Target Ulcer Pain | Week 06 | -15.56 units on a scale | Standard Error 1.35 |
| HP802-247 | Change in Target Ulcer Pain | Week 12 | -17.18 units on a scale | Standard Error 1.36 |
| HP802-247 | Change in Target Ulcer Pain | Week 01 | -5.08 units on a scale | Standard Error 1.08 |
| Vehicle | Change in Target Ulcer Pain | Week 12 | -16.39 units on a scale | Standard Error 1.35 |
| Vehicle | Change in Target Ulcer Pain | Week 01 | -5.05 units on a scale | Standard Error 1.08 |
| Vehicle | Change in Target Ulcer Pain | Week 02 | -6.95 units on a scale | Standard Error 1.24 |
| Vehicle | Change in Target Ulcer Pain | Week 09 | -15.97 units on a scale | Standard Error 1.31 |
| Vehicle | Change in Target Ulcer Pain | Week 03 | -9.58 units on a scale | Standard Error 1.26 |
| Vehicle | Change in Target Ulcer Pain | Week 04 | -10.26 units on a scale | Standard Error 1.29 |
| Vehicle | Change in Target Ulcer Pain | Week 05 | -13.17 units on a scale | Standard Error 1.22 |
| Vehicle | Change in Target Ulcer Pain | Week 06 | -13.03 units on a scale | Standard Error 1.34 |
| Vehicle | Change in Target Ulcer Pain | Week 07 | -14.51 units on a scale | Standard Error 1.37 |
| Vehicle | Change in Target Ulcer Pain | Week 08 | -14.81 units on a scale | Standard Error 1.37 |
| Vehicle | Change in Target Ulcer Pain | Week 10 | -15.91 units on a scale | Standard Error 1.31 |
| Vehicle | Change in Target Ulcer Pain | Week 11 | -16.47 units on a scale | Standard Error 1.32 |
Comparison: Week 01p-value: 0.9853ANCOVA
Comparison: Week 02p-value: 0.7083ANCOVA
Comparison: Week 03p-value: 0.6744ANCOVA
p-value: 0.2891ANCOVA
Comparison: Week 05p-value: 0.9923ANCOVA
Comparison: Week 06p-value: 0.1775ANCOVA
Comparison: Week 07p-value: 0.499ANCOVA
Comparison: Week 08p-value: 0.4423ANCOVA
Comparison: Week 09p-value: 0.5138ANCOVA
Comparison: Week 10p-value: 0.3409ANCOVA
Comparison: Week 11p-value: 0.6358ANCOVA
Comparison: Week 12p-value: 0.6753ANCOVA
Secondary
Compare the Efficacy of the Treatment Groups in Achieving Complete Wound Closure, Based on the Median Time (in Days) to Closure Over the 12-Week Treatment Period From Baseline.
This key secondary outcome was based on a Kaplan-Meier survival analysis.
Time frame: 12 weeks
Population: ITT Populations: Subjects who received at least one dose of test article. Data were analyzed using a Kaplan-Meier Survival Analysis, with significance being at P \< 0.05.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HP802-247 | Compare the Efficacy of the Treatment Groups in Achieving Complete Wound Closure, Based on the Median Time (in Days) to Closure Over the 12-Week Treatment Period From Baseline. | 57.0 days to wound closure |
| Vehicle | Compare the Efficacy of the Treatment Groups in Achieving Complete Wound Closure, Based on the Median Time (in Days) to Closure Over the 12-Week Treatment Period From Baseline. | 50.0 days to wound closure |
p-value: <0.05Kaplan-Meier Survival analysis
Secondary
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 and a Kaplan-Meier survival analysis.
Time frame: 12 Weeks
Population: ITT Populations: Subjects who received at least one dose of test article. Data were analyzed using the Cox Proportional hazard procedure, with significance being at P \< 0.05 and by the Kaplan-Meier survival procedure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HP802-247 | 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. | 57.0 days |
| Vehicle | 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. | 50.0 days |
p-value: 0.3675Regression, Cox
Secondary
Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline
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.
Time frame: Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first
Population: ITT Populations: Subjects who received at least one dose of test article. Analysis was by the Cochrane Mantel Haenszel (CMH) test, adjusted for sites, with significance being at P \< 0.05
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 02 | 5.7 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 06 | 38.9 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 10 | 53.6 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 07 | 40.8 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 03 | 13.3 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 08 | 46.4 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 01 | 2.4 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 09 | 49.3 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 04 | 23.7 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 11 | 57.8 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Baseline | 0 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 12 | 63.0 percentage of Closed Ulcers |
| HP802-247 | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 05 | 31.8 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 12 | 62.4 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Baseline | 0 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 01 | 1.9 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 02 | 9.5 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 03 | 19.5 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 04 | 32.4 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 05 | 38.1 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 06 | 44.3 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 07 | 47.6 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 08 | 52.9 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 10 | 55.7 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 11 | 60.0 percentage of Closed Ulcers |
| Vehicle | Compare the Treatment Groups for the Percentage of Closed Ulcers at Each Visit of the 12-Week Treatment Period From Baseline | Treatment Week 09 | 55.2 percentage of Closed Ulcers |
Comparison: Treatment Week 01p-value: 0.6426Cochran-Mantel-Haenszel
Comparison: Treatment Week 02p-value: 0.3843Cochran-Mantel-Haenszel
Comparison: Treatment Week 03p-value: 0.2792Cochran-Mantel-Haenszel
Comparison: Treatment Week 04p-value: 0.1502Cochran-Mantel-Haenszel
Comparison: Treatment Week 05p-value: 0.3823Cochran-Mantel-Haenszel
Comparison: Treatment Week 06p-value: 0.5528Cochran-Mantel-Haenszel
Comparison: Treatment Week 07p-value: 0.02913Cochran-Mantel-Haenszel
Comparison: Treatment Week 08p-value: 0.3896Cochran-Mantel-Haenszel
Comparison: Treatment Week 09p-value: 0.3989Cochran-Mantel-Haenszel
Comparison: Treatment Week 10p-value: 0.8682Cochran-Mantel-Haenszel
Comparison: Treatment Week 11p-value: 0.8083Cochran-Mantel-Haenszel
Comparison: Treatment Week 12p-value: 0.6687Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Target ulcer status observed at two and three months following initial ulcer closure.
Population: The 285 subjects (HP802-247: 141/222; Vehicle: 144/225) who completed the treatment period with confirmed wound closure.~Subjects returning for Visit 1 with confirmed wound closure at end of treatment: 134 HP802-247 and 132 Vehicle.~Subjects returning for Visit 2 with confirmed wound closure at end of treatment: 132 HP802-247 and 131 Vehicle
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HP802-247 | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 1 (2 months), Wounds Reopened | 14 participants |
| HP802-247 | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 1 (2 months), Wounds Closed | 120 participants |
| HP802-247 | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 2 (3 months), Wounds Reopened | 14 participants |
| HP802-247 | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 2 (3 months), Wounds Closed | 118 participants |
| Vehicle | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 2 (3 months), Wounds Reopened | 16 participants |
| Vehicle | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 1 (2 months), Wounds Closed | 114 participants |
| Vehicle | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 2 (3 months), Wounds Closed | 112 participants |
| Vehicle | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 1 (2 months), Wounds Reopened | 18 participants |