Venous Leg Ulcers
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). At least 250 subjects will participate. The study is going to be conducted in approximately 50 sites in the United States and Canada.
Detailed description
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 16-week treatment period. Vehicle looks the same as HP802-247 but contains no cells. Target wound status is evaluated at each study visit (closed, open, reopened). At wound closure or completion of treatment all subject will enter an observational safety followed up period which ends at one year after initial exposure to test article.
Interventions
BIOLOGICALHP802-247
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 x106 cells per mL every 14 days.
BIOLOGICALVehicle
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 \>12 cm2 to ≤ 36 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 |
|---|---|---|
| Wound Closure | 16 Weeks | Compare HP802-247 plus compression therapy against Vehicle plus compression therapy for proportion of subjects with complete wound closure over the 16-week treatment period from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time in Days to Closure | 16 Weeks | Compare the efficacy of HP802-247 plus compression therapy against Vehicle plus compression therapy in achieving complete wound closure, based on time in days to closure over the 16-week treatment period from baseline. |
Countries
Canada, Puerto Rico, United States
Participant flow
Recruitment details
Subjects were screened at 36 sites in the US and 3 in Canada; between November 30, 2012 and November 11, 2015; 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 solution) containing 0.5 x 106 cells per mL every 14 days. | 69 |
| Vehicle Vehicle Control(fibrinogen solution & thrombin solution without cells) | 70 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Moved from area | 2 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Progressive disease | 1 | 2 |
| Overall Study | Trial termination | 11 | 9 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | HP802-247 | Vehicle | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 32 Participants | 26 Participants | 58 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 44 Participants | 81 Participants |
| Age, Continuous | 62.4 years STANDARD_DEVIATION 15.1 | 61.0 years STANDARD_DEVIATION 12.1 | 61.7 years STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 15 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 55 Participants | 107 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 11 Participants | 24 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 | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 51 Participants | 58 Participants | 109 Participants |
| Region of Enrollment Canada | 4 participants | 3 participants | 7 participants |
| Region of Enrollment United States | 65 participants | 67 participants | 132 participants |
| Sex: Female, Male Female | 28 Participants | 32 Participants | 60 Participants |
| Sex: Female, Male Male | 41 Participants | 38 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 78 |
| other Total, other adverse events | 23 / 77 | 19 / 78 |
| serious Total, serious adverse events | 7 / 77 | 7 / 78 |
Outcome results
Primary
Wound Closure
Compare HP802-247 plus compression therapy against Vehicle plus compression therapy for proportion of subjects with complete wound closure over the 16-week treatment period from baseline.
Time frame: 16 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HP802-247 | Wound Closure | 17 participants |
| Vehicle | Wound Closure | 23 participants |
Secondary
Time in Days to Closure
Compare the efficacy of HP802-247 plus compression therapy against Vehicle plus compression therapy in achieving complete wound closure, based on time in days to closure over the 16-week treatment period from baseline.
Time frame: 16 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HP802-247 | Time in Days to Closure | 83.4 Days | Standard Deviation 33.8 |
| Vehicle | Time in Days to Closure | 87.1 Days | Standard Deviation 42.5 |