Venous Ulcer, Venous Stasis Ulcer, Ulcer
Conditions
Keywords
Venous leg ulcer, ulcer, venous stasis, compression, venous, venous stasis ulcer, vlu, wound, varicose veins, venous insufficiency, dvt, deep vein thrombosis
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. 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
See Brief Summary
Interventions
BIOLOGICALHP802-247
Study Dosage / Usage: 260 µL (130 µL, one spray, of each solution) containing 0.5 X 10(6th) cells per mL every 14 days.
OTHERHP802-247 Vehicle
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.
Sponsors
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 Number of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline | Weekly, over 12 Weeks or until wound closure, which ever occurred first | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 12 weeks | This key secondary outcome was based on a Kaplan-Meier Survival analysis. |
| Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first | 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. |
| 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. |
| Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Baseline and 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. |
| Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Baseline and Weekly, over the 12 week treatment period | 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. |
| Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Target ulcer status observed at two (visit 1) and three (visit 2) 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. |
Countries
Belgium, Czechia, Germany, Hungary, Poland
Participant flow
Recruitment details
Subjects were screened at 47 sites in the EU \[Belgium (3), Czech Republic (8), Germany (15), Hungary (8), Poland (13)\] between January 10, 2014 and November 27, 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 Plus Compression Therapy 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 for up to 12 weeks or wound closure, which ever occurred first. Subjects randomized to HP802-247 will receive Vehicle on alternate weeks.
HP802-247: Study Dosage / Usage: 260 µL (130 µL, one spray, of each solution) containing 0.5 X 10(6th) cells per mL every 14 days. | 131 |
| HP802-247 Vehicle Plus Compression Therapy fibrinogen solution & thrombin solution without cells. Subjects randomized to HP802-247 Vehicle will receive Vehicle weekly for up to 12 weeks or wound closure, which ever occurred first.
HP802-247 Vehicle: 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. | 121 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Completed Follow up Visit 1 | Early Termination | 13 | 9 |
| Completed Follow up Visit 1 | Withdrawal by Subject | 1 | 0 |
| Completed Follow up Visit 2 | Adverse Event | 1 | 0 |
| Completed Follow up Visit 2 | Death | 1 | 0 |
| Completed Follow up Visit 2 | Lost to Follow-up | 0 | 1 |
| Completed Follow up Visit 2 | Withdrawal by Subject | 1 | 2 |
| Randomized | Adverse Event | 5 | 3 |
| Randomized | Death | 1 | 2 |
| Randomized | Lost to Follow-up | 1 | 1 |
| Randomized | Other | 3 | 3 |
| Randomized | Sponsor Decision | 47 | 34 |
| Randomized | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | HP802-247 Plus Compression Therapy | HP802-247 Vehicle Plus Compression Therapy | Total |
|---|---|---|---|
| Age, Continuous | 65.6 years | 68.1 years | 66.8 years |
| Age, Customized 18-39 years | 6 participants | 3 participants | 9 participants |
| Age, Customized 40-49 years | 6 participants | 3 participants | 9 participants |
| Age, Customized 50-59 years | 26 participants | 20 participants | 46 participants |
| Age, Customized 60-69 years | 40 participants | 40 participants | 80 participants |
| Age, Customized 70+ years | 53 participants | 55 participants | 108 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 129 Participants | 120 Participants | 249 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 131 Participants | 121 Participants | 252 Participants |
| Sex: Female, Male Female | 76 Participants | 63 Participants | 139 Participants |
| Sex: Female, Male Male | 55 Participants | 58 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 60 / 131 | 64 / 121 |
| serious Total, serious adverse events | 5 / 131 | 12 / 121 |
Outcome results
Primary
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.
Time frame: Weekly, over 12 Weeks or until wound closure, which ever occurred first
Population: ITT Populations: Subjects who received at least one dose of test article.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Number of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline | Wounds Not Closed | 70 participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Number of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline | Wounds Closed | 61 participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Number of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline | Wounds Closed | 61 participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Number of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline | Wounds Not Closed | 60 participants |
p-value: 0.5348Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline and Weekly, over the 12 week treatment period
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 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 02 | -2.2 mm | Standard Error 2.3 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 07 | -13.1 mm | Standard Error 2.2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 04 | -10.1 mm | Standard Error 2.2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 08 | -14.2 mm | Standard Error 2.1 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 01 | -4.1 mm | Standard Error 2.3 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 09 | -10.1 mm | Standard Error 2.2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 05 | -9.7 mm | Standard Error 2.3 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 10 | -12.7 mm | Standard Error 2.1 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 03 | -9.2 mm | Standard Error 2.2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 11 | -12.9 mm | Standard Error 2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 06 | -12.2 mm | Standard Error 2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 12 | -14.3 mm | Standard Error 2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Baseline | 24.18 mm | Standard Error 27 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 12 | -12.2 mm | Standard Error 2.1 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Baseline | 22.35 mm | Standard Error 16 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 01 | -4.9 mm | Standard Error 2.4 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 02 | -1.3 mm | Standard Error 2.4 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 03 | -5.3 mm | Standard Error 2.3 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 04 | -8.8 mm | Standard Error 2.2 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 05 | -8.6 mm | Standard Error 2.3 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 06 | -9.1 mm | Standard Error 2.1 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 07 | -8.9 mm | Standard Error 2.2 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 08 | -9.0 mm | Standard Error 2.1 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 09 | -6.3 mm | Standard Error 2.3 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 10 | -11.1 mm | Standard Error 2.2 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks | Week 11 | -11.8 mm | Standard Error 2.1 |
p-value: 0.7439ANCOVA
p-value: 0.6992ANCOVA
p-value: 0.0867ANCOVA
p-value: 0.5739ANCOVA
p-value: 0.6497ANCOVA
p-value: 0.1427ANCOVA
p-value: 0.0682ANCOVA
p-value: 0.0161ANCOVA
p-value: 0.0973ANCOVA
p-value: 0.4661ANCOVA
p-value: 0.601ANCOVA
p-value: 0.3369ANCOVA
Secondary
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.
Time frame: Baseline and Weekly, over the 12 week treatment period
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 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 02 | -10.4 mm | Standard Error 2.2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 07 | -18.5 mm | Standard Error 2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 04 | -14.3 mm | Standard Error 2.3 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 08 | -20.0 mm | Standard Error 2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 01 | -8.6 mm | Standard Error 2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 09 | -19.7 mm | Standard Error 2.1 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 05 | -17.2 mm | Standard Error 2.1 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 10 | -18.9 mm | Standard Error 2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 03 | -14.0 mm | Standard Error 2.3 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 11 | -19.4 mm | Standard Error 2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 06 | -17.8 mm | Standard Error 2.2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 12 | -20.0 mm | Standard Error 2 |
| HP802-247 Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Baseline | 29.40 mm | Standard Error 28.5 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 12 | -20.1 mm | Standard Error 2 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Baseline | 26.30 mm | Standard Error 28.3 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 01 | -7.5 mm | Standard Error 2.1 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 02 | -11.0 mm | Standard Error 2.3 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 03 | -10.7 mm | Standard Error 2.4 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 04 | -12.1 mm | Standard Error 2.3 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 05 | -13.6 mm | Standard Error 2.2 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 06 | -15.4 mm | Standard Error 2.2 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 07 | -17.5 mm | Standard Error 2.1 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 08 | -17.1 mm | Standard Error 2.1 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 09 | -17.9 mm | Standard Error 2.1 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 10 | -18.4 mm | Standard Error 2.1 |
| HP802-247 Vehicle Plus Compression Therapy | Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks | Week 11 | -19.7 mm | Standard Error 2.1 |
p-value: 0.5909ANCOVA
p-value: 0.8234ANCOVA
p-value: 0.1556ANCOVA
p-value: 0.3487ANCOVA
p-value: 0.1064ANCOVA
p-value: 0.2888ANCOVA
p-value: 0.6095ANCOVA
p-value: 0.1566ANCOVA
p-value: 0.4216ANCOVA
p-value: 0.8166ANCOVA
p-value: 0.9114ANCOVA
p-value: 0.9733ANCOVA
Secondary
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.
Time frame: 12 weeks
Population: ITT Populations: Subjects who received at least one dose of test article. Data were analyzed using Kaplan-Meier Survival analysis, with significance being at P \< 0.05.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HP802-247 Plus Compression Therapy | 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. | 64 days |
| HP802-247 Vehicle Plus Compression Therapy | 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. | 57 days |
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.
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HP802-247 Plus Compression Therapy | 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 |
| HP802-247 Vehicle Plus Compression Therapy | 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: 0.9456Regression, Cox
Secondary
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.
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 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 11 | 41.2 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Baseline | 0 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 01 | 2.3 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 02 | 8.4 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 03 | 13.7 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 04 | 22.1 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 05 | 26.7 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 06 | 29.8 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 07 | 32.8 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 08 | 37.4 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 09 | 38.9 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 10 | 40.5 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 12 | 48.1 percentage of participants |
| HP802-247 Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Week 12 - Primary Endpoint | 46.6 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 09 | 43.8 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 11 | 47.9 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 06 | 38.0 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Baseline | 0 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 12 | 53.7 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 01 | 3.3 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 07 | 39.7 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 02 | 7.4 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 10 | 46.3 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 03 | 18.2 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 08 | 39.7 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 04 | 25.6 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Week 12 - Primary Endpoint | 50.4 percentage of participants |
| HP802-247 Vehicle Plus Compression Therapy | Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline | Treatment Week 05 | 33.9 percentage of participants |
p-value: 0.6194Cochran-Mantel-Haenszel
p-value: 0.793Cochran-Mantel-Haenszel
p-value: 0.3362Cochran-Mantel-Haenszel
p-value: 0.5263Cochran-Mantel-Haenszel
p-value: 0.1997Cochran-Mantel-Haenszel
p-value: 0.1617Cochran-Mantel-Haenszel
p-value: 0.2611Cochran-Mantel-Haenszel
p-value: 0.7232Cochran-Mantel-Haenszel
p-value: 0.4405Cochran-Mantel-Haenszel
p-value: 0.3516Cochran-Mantel-Haenszel
p-value: 0.2821Cochran-Mantel-Haenszel
p-value: 0.3722Cochran-Mantel-Haenszel
p-value: 0.5348Cochran-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 (visit 1) and three (visit 2) months following initial ulcer closure.
Population: Due to study termination the data available to assess durability of closure were limited to only the subjects who completed at least one of the follow-up visits. Participants who had CLOSED wounds at completion of treatment; 103 subjects (HP802-247: 49; Vehicle: 54) completed Visit 18, 114 subjects (HP802-247: 57; Vehicle: 57) completed Visit 19
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HP802-247 Plus Compression Therapy | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 1 (wounds remained closed) | 45 participants |
| HP802-247 Plus Compression Therapy | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 1 (wounds reopened) | 4 participants |
| HP802-247 Plus Compression Therapy | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 2 (wounds remained closed) | 51 participants |
| HP802-247 Plus Compression Therapy | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 2 (wounds reopened) | 6 participants |
| HP802-247 Vehicle Plus Compression Therapy | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 2 (wounds reopened) | 10 participants |
| HP802-247 Vehicle Plus Compression Therapy | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 1 (wounds remained closed) | 52 participants |
| HP802-247 Vehicle Plus Compression Therapy | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 2 (wounds remained closed) | 47 participants |
| HP802-247 Vehicle Plus Compression Therapy | Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure | Follow-up Visit 1 (wounds reopened) | 2 participants |