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Safety and Efficacy Trial of HP802-247 in the Treatment of Chronic Venous Leg Ulcers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01853384
Recruitment Status : Terminated (based on outcome of trial NCT01656889.)
First Posted : May 15, 2013
Results First Posted : October 3, 2016
Last Update Posted : October 3, 2016
Sponsor:
Information provided by (Responsible Party):
Healthpoint

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Venous Ulcer
Venous Stasis Ulcer
Ulcer
Interventions Biological: HP802-247
Other: HP802-247 Vehicle
Enrollment 252
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.
Arm/Group Title HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Hide Arm/Group 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 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.

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.

Period Title: Randomized
Started 131 121
Completed 69 75
Not Completed 62 46
Reason Not Completed
Adverse Event             5             3
Death             1             2
Lost to Follow-up             1             1
Withdrawal by Subject             5             3
Sponsor Decision             47             34
Other             3             3
Period Title: Enrolled in Follow up Period
Started 96 94
Not Enrolled in Follow-up 35 27
Completed 96 94
Not Completed 0 0
Period Title: Completed Follow up Visit 1
Started 96 94
Completed 82 85
Not Completed 14 9
Reason Not Completed
Early Termination             13             9
Withdrawal by Subject             1             0
Period Title: Completed Follow up Visit 2
Started 96 94
Completed 93 91
Not Completed 3 3
Reason Not Completed
Adverse Event             1             0
Withdrawal by Subject             1             2
Death             1             0
Lost to Follow-up             0             1
Arm/Group Title HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy Total
Hide Arm/Group 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 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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 131 121 252
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 131 participants 121 participants 252 participants
65.6
(28 to 90)
68.1
(28 to 92)
66.8
(28 to 92)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 131 participants 121 participants 252 participants
18-39 years 6 3 9
40-49 years 6 3 9
50-59 years 26 20 46
60-69 years 40 40 80
70+ years 53 55 108
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 131 participants 121 participants 252 participants
Female
76
  58.0%
63
  52.1%
139
  55.2%
Male
55
  42.0%
58
  47.9%
113
  44.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 131 participants 121 participants 252 participants
Hispanic or Latino
1
   0.8%
0
   0.0%
1
   0.4%
Not Hispanic or Latino
129
  98.5%
120
  99.2%
249
  98.8%
Unknown or Not Reported
1
   0.8%
1
   0.8%
2
   0.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 131 participants 121 participants 252 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
131
 100.0%
121
 100.0%
252
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Compare the Treatment Groups for the Number of Subjects With Complete Wound Closure Over the 12-Week Treatment Period From Baseline
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Populations: Subjects who received at least one dose of test article.
Arm/Group Title HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 131 121
Measure Type: Number
Unit of Measure: participants
Wounds Closed 61 61
Wounds Not Closed 70 60
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .5348
Comments Analysis adjusted for sites, with significance being at P < 0.05
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Secondary Outcome
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.
Hide Description This key secondary outcome was based on a Cox Proportional Hazard Analysis.
Time Frame 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 131 121
Median (Full Range)
Unit of Measure: days
57.0
(8.0 to 115.0)
50.0
(6.0 to 134.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .9456
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
3.Secondary Outcome
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.
Hide Description This key secondary outcome was based on a Kaplan-Meier Survival analysis.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 131 121
Median (95% Confidence Interval)
Unit of Measure: days
64
(57 to 78)
57
(50 to 71)
4.Secondary Outcome
Title Compare the Treatment Groups for the Proportion of Subjects With Wound Closure at Each of the 12-Week Treatment Period From Baseline
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 131 121
Measure Type: Number
Unit of Measure: percentage of participants
Baseline 0 0
Treatment Week 01 2.3 3.3
Treatment Week 02 8.4 7.4
Treatment Week 03 13.7 18.2
Treatment Week 04 22.1 25.6
Treatment Week 05 26.7 33.9
Treatment Week 06 29.8 38.0
Treatment Week 07 32.8 39.7
Treatment Week 08 37.4 39.7
Treatment Week 09 38.9 43.8
Treatment Week 10 40.5 46.3
Treatment Week 11 41.2 47.9
Treatment Week 12 48.1 53.7
Week 12 - Primary Endpoint 46.6 50.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .6194
Comments Treatment Week 01
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .7930
Comments Treatment Week 02
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3362
Comments Treatment Week 03
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5263
Comments Treatment Week 04
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1997
Comments Treatment Week 05
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1617
Comments Treatment Week 06
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2611
Comments Treatment Week 07
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7232
Comments Treatment Week 08
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4405
Comments Treatment Week 09
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3516
Comments Treatment Week 10
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2821
Comments Treatment Week 11
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3722
Comments Treatment Week 12
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5348
Comments Week 12 - Primary Endpoint
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
5.Secondary Outcome
Title Number of Subjects With Durable Wound Healing Over the 3 Months Following Complete Wound Closure
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 134 132
Measure Type: Number
Unit of Measure: participants
Follow-up Visit 1 (wounds remained closed) 45 52
Follow-up Visit 1 (wounds reopened) 4 2
Follow-up Visit 2 (wounds remained closed) 51 47
Follow-up Visit 2 (wounds reopened) 6 10
6.Secondary Outcome
Title Change From Baseline in Pain Associated With the Target Wound at Each of the 12 Double Blind Treatment Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 131 121
Least Squares Mean (Standard Error)
Unit of Measure: mm
Baseline 29.40  (28.5) 26.30  (28.3)
Week 01 -8.6  (2) -7.5  (2.1)
Week 02 -10.4  (2.2) -11.0  (2.3)
Week 03 -14.0  (2.3) -10.7  (2.4)
Week 04 -14.3  (2.3) -12.1  (2.3)
Week 05 -17.2  (2.1) -13.6  (2.2)
Week 06 -17.8  (2.2) -15.4  (2.2)
Week 07 -18.5  (2.0) -17.5  (2.1)
Week 08 -20.0  (2.0) -17.1  (2.1)
Week 09 -19.7  (2.1) -17.9  (2.1)
Week 10 -18.9  (2.0) -18.4  (2.1)
Week 11 -19.4  (2.0) -19.7  (2.1)
Week 12 -20.0  (2.0) -20.1  (2.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5909
Comments Week 01
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8234
Comments Week 02
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1556
Comments Week 03
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3487
Comments Week 04
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1064
Comments Week 05
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2888
Comments Week 06
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6095
Comments Week 07
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1566
Comments Week 08
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4216
Comments Week 09
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8166
Comments Week10
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9114
Comments Week 11
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9733
Comments Week 12
Method ANCOVA
Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Pain Associated With the Target Leg at Each of the 12 Double Blind Treatment Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 131 121
Least Squares Mean (Standard Error)
Unit of Measure: mm
Baseline 24.18  (27.0) 22.35  (16.0)
Week 01 -4.1  (2.3) -4.9  (2.4)
Week 02 -2.2  (2.3) -1.3  (2.4)
Week 03 -9.2  (2.2) -5.3  (2.3)
Week 04 -10.1  (2.2) -8.8  (2.2)
Week 05 -9.7  (2.3) -8.6  (2.3)
Week 06 -12.2  (2.0) -9.1  (2.1)
Week 07 -13.1  (2.2) -8.9  (2.2)
Week 08 -14.2  (2.1) -9.0  (2.1)
Week 09 -10.1  (2.2) -6.3  (2.3)
Week 10 -12.7  (2.1) -11.1  (2.2)
Week 11 -12.9  (2.0) -11.8  (2.1)
Week 12 -14.3  (2.0) -12.2  (2.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7439
Comments Week 01
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6992
Comments Week 02
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0867
Comments Week 03
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5739
Comments Week 04
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6497
Comments Week 05
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1427
Comments Week 06
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0682
Comments Week 07
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0161
Comments Week 08
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0973
Comments Week 09
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4661
Comments Week 10
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6010
Comments Week 11
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection HP802-247 Plus Compression Therapy, HP802-247 Vehicle Plus Compression Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3369
Comments Week 12
Method ANCOVA
Comments [Not Specified]
Time Frame Up to 19 Weeks or subjects who completed 12 weeks of treatment and the post-treatment follow up. For subjects who had wound closure, collection time included the treatment period and the post-treatment period
Adverse Event Reporting Description All subjects randomized to treatment were questioned about adverse events and were included in the number of participants assessed for safety. The first assessments at each weekly visit were about changes in general health and concomitant medications and the occurrence of adverse events.
 
Arm/Group Title HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Hide Arm/Group 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 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.

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.

All-Cause Mortality
HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/131 (3.82%)      12/121 (9.92%)    
Cardiac disorders     
Angina pectoris  1  0/131 (0.00%)  0 1/121 (0.83%)  1
Arrhythmia  1  1/131 (0.76%)  1 0/121 (0.00%)  0
Cardiac arrest  1  1/131 (0.76%)  1 0/121 (0.00%)  0
Cardiac failure  1  0/131 (0.00%)  0 1/121 (0.83%)  1
Gastrointestinal disorders     
Small intestinal obstruction  1  0/131 (0.00%)  0 1/121 (0.83%)  1
General disorders     
Oedema peripheral  1  0/131 (0.00%)  0 1/121 (0.83%)  2
Infections and infestations     
Erysipelas  1  0/131 (0.00%)  0 1/121 (0.83%)  1
Gangrene  1  1/131 (0.76%)  1 0/121 (0.00%)  0
Pneumonia  1  0/131 (0.00%)  0 1/121 (0.83%)  1
Wound sepsis  1  0/131 (0.00%)  0 1/121 (0.83%)  1
Injury, poisoning and procedural complications     
Humerus fracture  1  1/131 (0.76%)  1 0/121 (0.00%)  0
Lower limb fracture  1  1/131 (0.76%)  1 0/121 (0.00%)  0
Multiple injuries  1  0/131 (0.00%)  0 2/121 (1.65%)  2
Traumatic haematoma  1  0/131 (0.00%)  0 1/121 (0.83%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastases to lung  1  1/131 (0.76%)  1 0/121 (0.00%)  0
Vulval cancer  1  1/131 (0.76%)  1 0/121 (0.00%)  0
Reproductive system and breast disorders     
Metrorrhagia  1  0/131 (0.00%)  0 1/121 (0.83%)  1
Skin and subcutaneous tissue disorders     
Dermatitis contact  1  0/131 (0.00%)  0 1/121 (0.83%)  1
Pemphigoid  1  0/131 (0.00%)  0 1/121 (0.83%)  1
Purpura  1  0/131 (0.00%)  0 1/121 (0.83%)  1
Skin ulcer  1  1/131 (0.76%)  1 0/121 (0.00%)  0
Stasis dermatitis  1  0/131 (0.00%)  0 1/121 (0.83%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v 13.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
HP802-247 Plus Compression Therapy HP802-247 Vehicle Plus Compression Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   60/131 (45.80%)      64/121 (52.89%)    
Gastrointestinal disorders     
Gastrointestinal disorders  1  5/131 (3.82%)  9 6/121 (4.96%)  8
General disorders     
General disorders and administration site conditions  1  3/131 (2.29%)  3 9/121 (7.44%)  11
Infections and infestations     
Infections and infestations  1  15/131 (11.45%)  20 19/121 (15.70%)  23
Infected skin ulcer  1  7/131 (5.34%)  9 5/121 (4.13%)  7
Injury, poisoning and procedural complications     
Injury, poisoning and procedural complications  1  18/131 (13.74%)  22 13/121 (10.74%)  13
Excoriation  1  10/131 (7.63%)  12 6/121 (4.96%)  6
Metabolism and nutrition disorders     
Metabolism and nutrition disorders  1  2/131 (1.53%)  2 4/121 (3.31%)  4
Musculoskeletal and connective tissue disorders     
Musculoskeletal and connective tissue disorders  1  9/131 (6.87%)  13 14/121 (11.57%)  19
Pain in extremity  1  5/131 (3.82%)  6 12/121 (9.92%)  15
Nervous system disorders     
Nervous system disorders  1  2/131 (1.53%)  7 4/121 (3.31%)  4
Skin and subcutaneous tissue disorders     
Skin and subcutaneous tissue disorders  1  30/131 (22.90%)  62 39/121 (32.23%)  87
Dermatitis  1  4/131 (3.05%)  6 1/121 (0.83%)  2
Erythema  1  4/131 (3.05%)  4 5/121 (4.13%)  6
Skin maceration  1  2/131 (1.53%)  3 7/121 (5.79%)  13
Skin ulcer  1  17/131 (12.98%)  34 20/121 (16.53%)  37
Venous ulcer pain  1  6/131 (4.58%)  6 3/121 (2.48%)  3
Vascular disorders     
Vascular disorders  1  5/131 (3.82%)  8 10/121 (8.26%)  11
Hypertension  1  5/131 (3.82%)  8 7/121 (5.79%)  8
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v 13.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jaime E Dickerson, PhD
Organization: Smith & Nephew, Inc
Phone: 1-817-302-3914
EMail: Jaime.Dickerson@smith-nephew.com
Layout table for additonal information
Responsible Party: Healthpoint
ClinicalTrials.gov Identifier: NCT01853384    
Other Study ID Numbers: 802-247-09-032
2012-003286-18 ( EudraCT Number )
First Submitted: May 8, 2013
First Posted: May 15, 2013
Results First Submitted: September 19, 2016
Results First Posted: October 3, 2016
Last Update Posted: October 3, 2016