Back to resultsSafety and Efficacy Trial of HP802-247 in the Treatment of Chronic Venous Leg Ulcers
Primary Purpose
Venous Ulcer, Venous Stasis Ulcer, Ulcer
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
HP802-247
HP802-247 Vehicle
Sponsored by
About this trial
This is an interventional treatment trial for Venous Ulcer focused on measuring Venous leg ulcer, ulcer, venous stasis, compression, venous, venous stasis ulcer, vlu, wound, varicose veins, venous insufficiency, dvt, deep vein thrombosis
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
HP802-247 plus compression therapy
HP802-247 Vehicle plus compression therapy
Arm Description
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.
fibrinogen solution & thrombin solution without cells. Subjects randomized to HP802-247 Vehicle will receive Vehicle weekly.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01853384
Brief Title
Safety and Efficacy Trial of HP802-247 in the Treatment of Chronic Venous Leg Ulcers
Official Title
A Phase 3 Randomized Safety and Efficacy Trial of HP802-247 in the Treatment of Chronic Venous Leg Ulcers (EU)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Terminated
Why Stopped
based on outcome of trial NCT01656889.
Study Start Date
November 2013 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
February 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Healthpoint
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Ulcer, Venous Stasis Ulcer, Ulcer
Keywords
Venous leg ulcer, ulcer, venous stasis, compression, venous, venous stasis ulcer, vlu, wound, varicose veins, venous insufficiency, dvt, deep vein thrombosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
252 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HP802-247 plus compression therapy
Arm Type
Experimental
Arm Description
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.
Arm Title
HP802-247 Vehicle plus compression therapy
Arm Type
Placebo Comparator
Arm Description
fibrinogen solution & thrombin solution without cells. Subjects randomized to HP802-247 Vehicle will receive Vehicle weekly.
Intervention Type
Biological
Intervention Name(s)
HP802-247
Intervention Description
Study Dosage / Usage: 260 µL (130 µL, one spray, of each solution) containing 0.5 X 10(6th) cells per mL every 14 days.
Intervention Type
Other
Intervention Name(s)
HP802-247 Vehicle
Other Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Compare the Treatment Groups for the Number of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline
Description
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
Secondary Outcome Measure Information:
Title
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.
Description
This key secondary outcome was based on a Cox Proportional Hazard Analysis.
Time Frame
12 Weeks
Title
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.
Description
This key secondary outcome was based on a Kaplan-Meier Survival analysis.
Time Frame
12 weeks
Title
Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline
Description
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
Title
Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure
Description
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.
Title
Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks
Description
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
Title
Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Herbert B. Slade, MD
Organizational Affiliation
Smith & Nephew, Inc.
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Tommy Lee, MSHS
Organizational Affiliation
Smith & Nephew, Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Wolfgang Vanscheidt, Professor Dr
Organizational Affiliation
University Freiburg-Practice for Dermatology
Official's Role
Principal Investigator
Facility Information:
City
Anderlecht
Country
Belgium
City
Brussels
Country
Belgium
City
Edegen
Country
Belgium
City
Gent
Country
Belgium
City
Kortrijk
Country
Belgium
City
Brno
Country
Czech Republic
City
Hradec Kralove
Country
Czech Republic
City
Olomouc
Country
Czech Republic
City
Pardubice
Country
Czech Republic
City
Plzen-Bory
Country
Czech Republic
City
Praha
Country
Czech Republic
City
Trebic
Country
Czech Republic
City
Uherske Hradiste
Country
Czech Republic
City
Usti nad Labem
Country
Czech Republic
City
Bochum
Country
Germany
City
Bonn
Country
Germany
City
Dresden
Country
Germany
City
Duesseldorf
Country
Germany
City
Essen
Country
Germany
City
Freiburg
Country
Germany
City
Goettingen
Country
Germany
City
Greifswald
Country
Germany
City
Hamburg
Country
Germany
City
Kiel
Country
Germany
City
Koeln
Country
Germany
City
Krefeld
Country
Germany
City
Magdeburg
Country
Germany
City
Muenchen
Country
Germany
City
Muenster
Country
Germany
City
Budapest
Country
Hungary
City
Debrecen
Country
Hungary
City
Hatvan
Country
Hungary
City
Oroshaza
Country
Hungary
City
Satoraljaujhely
Country
Hungary
City
Szeged
Country
Hungary
City
Szolnok
Country
Hungary
City
Katowice
Country
Poland
City
Krakow
Country
Poland
City
Lodz
Country
Poland
City
Lublin
Country
Poland
City
Poznan
Country
Poland
City
Rzeszow
Country
Poland
City
Studzionka
Country
Poland
City
Warsaw
Country
Poland
City
Warszawa
Country
Poland
City
Wroclaw
Country
Poland
City
Zabrze
Country
Poland
12. IPD Sharing Statement
Citations:
PubMed Identifier
29037354
Citation
Marston WA, Ennis WJ, Lantis JC 2nd, Kirsner RS, Galiano RD, Vanscheidt W, Eming SA, Malka M, Cargill DI, Dickerson JE Jr, Slade HB; HP802-247 Study Group. Baseline factors affecting closure of venous leg ulcers. J Vasc Surg Venous Lymphat Disord. 2017 Nov;5(6):829-835.e1. doi: 10.1016/j.jvsv.2017.06.017.
Results Reference
derived
Learn more about this trial
Safety and Efficacy Trial of HP802-247 in the Treatment of Chronic Venous Leg Ulcers
We'll reach out to this number within 24 hrs