Trial Outcomes & Findings for Ph 3 Efficacy and Safety of B-VEC for the Treatment of DEB (NCT NCT04491604)
NCT ID: NCT04491604
Last Updated: 2023-02-17
Results Overview
The primary wound was defined as a responder wound that met either of the following conditions: * Complete wound healing on Week 22 and Week 24, or * Complete wound healing on Week 24 and Week 26. For subjects with missing primary wound healing data, a multiple imputation approach (10 repliates) was used. The total numbers of primary wounds with complete healing for B-VEC and Placebo presented below were the average of those from the multiple imputation replicates, and therefore, they would not be whole numbers (integers).
COMPLETED
PHASE3
31 participants
26 weeks post-baseline
2023-02-17
Participant Flow
Unit of analysis: Wounds
Participant milestones
| Measure |
All Participants ("Topical Beremagene Geperpavec (B-VEC)", and "Placebo")
Each subject provided one pair of primary target wounds, with one wound from each pair randomized to be treated with B-VEC and the other wound with placebo.
|
|---|---|
|
Overall Study
STARTED
|
31 62
|
|
Overall Study
B-VEC
|
31 31
|
|
Overall Study
Placebo
|
31 31
|
|
Overall Study
COMPLETED
|
28 56
|
|
Overall Study
NOT COMPLETED
|
3 6
|
Reasons for withdrawal
| Measure |
All Participants ("Topical Beremagene Geperpavec (B-VEC)", and "Placebo")
Each subject provided one pair of primary target wounds, with one wound from each pair randomized to be treated with B-VEC and the other wound with placebo.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
Baseline Characteristics
Ph 3 Efficacy and Safety of B-VEC for the Treatment of DEB
Baseline characteristics by cohort
| Measure |
All Participants ("Topical Beremagene Geperpavec (B-VEC)", and "Placebo")
n=31 Participants
Each subject provided one pair of primary target wounds, with one wound from each pair randomized to be treated with B-VEC and the other wound with placebo.
|
|---|---|
|
Age, Continuous
|
17.2 years
STANDARD_DEVIATION 10.70 • n=5 Participants
|
|
Age, Customized
<= 12 years
|
10 Participants
n=5 Participants
|
|
Age, Customized
> 12 and <= 18 years
|
9 Participants
n=5 Participants
|
|
Age, Customized
> 18 years
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
31 participants
n=5 Participants
|
|
Primary Wound Area(cm^2) B-VEC
|
14.354 cm^2
STANDARD_DEVIATION 12.6930 • n=5 Participants
|
|
Primary Wound Area(cm^2) Placebo
|
15.565 cm^2
STANDARD_DEVIATION 12.1315 • n=5 Participants
|
PRIMARY outcome
Timeframe: 26 weeks post-baselinePopulation: The intent-to-treat (ITT) population included subjects whose primary wounds were randomized regardless of whether they received randomized treatment or not.
The primary wound was defined as a responder wound that met either of the following conditions: * Complete wound healing on Week 22 and Week 24, or * Complete wound healing on Week 24 and Week 26. For subjects with missing primary wound healing data, a multiple imputation approach (10 repliates) was used. The total numbers of primary wounds with complete healing for B-VEC and Placebo presented below were the average of those from the multiple imputation replicates, and therefore, they would not be whole numbers (integers).
Outcome measures
| Measure |
B-VEC
n=31 Wounds
Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein
|
Placebo
n=31 Wounds
Matching masked inactive topical gel
|
|---|---|---|
|
Primary Wound With Complete Wound Healing (100% Wound Closure) on Weeks 22 and 24 or Weeks 24 and 26
|
20.9 number of wounds with complete healing
|
6.7 number of wounds with complete healing
|
SECONDARY outcome
Timeframe: 12 weeks post-baselinePopulation: The intent-to-treat (ITT) population included subjects whose primary wounds were randomized regardless of whether they received randomized treatment or not.
The primary wound was defined as a responder wound that met either of the following conditions: * Complete wound healing on Week 8 and Week 10, or * Complete wound healing on Week 10 and Week 12. For subjects with missing primary wound healing data, a multiple imputation approach (10 repliates) was used. The total numbers of primary wounds with complete healing for B-VEC and Placebo presented below were the average of those from the multiple imputation replicates, and therefore, they would not be whole numbers (integers).
Outcome measures
| Measure |
B-VEC
n=31 Wounds
Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein
|
Placebo
n=31 Wounds
Matching masked inactive topical gel
|
|---|---|---|
|
Primary Wound With Complete Wound Healing (100% Wound Closure) on Weeks 8 and 10 or Weeks 10 and 12
|
21.9 number of wounds with complete healing
|
6.1 number of wounds with complete healing
|
SECONDARY outcome
Timeframe: 26 weeks post-baselinePopulation: The intent-to-treat (ITT) population included subjects whose primary wounds were randomized regardless of whether they received randomized treatment or not. For pain severity, only subjects ages 6 and above were evaluated (n=27). The analyses were based on observed data where missing data were not imputed, therefore the numbers of available data for analyses could be less than the total.
Changes from baseline at Weeks 22, 24, and 26 in primary wound pain severity (visual analog scale (VAS)) for ages 6 and above subjects. The Visual Analog Scale scores from 0 (no pain) to 10 (the worst possible pain). Negative values in changes from baseline mean improvement in pain severity.
Outcome measures
| Measure |
B-VEC
n=27 Participants
Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein
|
Placebo
n=27 Participants
Matching masked inactive topical gel
|
|---|---|---|
|
Primary Wound Pain Severity (Visual Analog Scale (VAS)) Change for Ages 6 and Above Subjects at Weeks 22, 24, and 26.
Week 22
|
-0.88 score on a scale of 0 to 10
Standard Deviation 2.346
|
-0.71 score on a scale of 0 to 10
Standard Deviation 2.476
|
|
Primary Wound Pain Severity (Visual Analog Scale (VAS)) Change for Ages 6 and Above Subjects at Weeks 22, 24, and 26.
Week 24
|
-0.64 score on a scale of 0 to 10
Standard Deviation 2.325
|
-0.08 score on a scale of 0 to 10
Standard Deviation 2.548
|
|
Primary Wound Pain Severity (Visual Analog Scale (VAS)) Change for Ages 6 and Above Subjects at Weeks 22, 24, and 26.
Week 26
|
-0.63 score on a scale of 0 to 10
Standard Deviation 2.123
|
-0.38 score on a scale of 0 to 10
Standard Deviation 2.871
|
Adverse Events
All Participants ("Topical Beremagene Geperpavec (B-VEC)", and "Placebo")
Serious adverse events
| Measure |
All Participants ("Topical Beremagene Geperpavec (B-VEC)", and "Placebo")
n=31 participants at risk
Each subject provided one pair of primary target wounds, with one wound from each pair randomized to be treated with B-VEC and the other wound with placebo. Due to the 'split-person'/intrasubject design, each subject received both B-VEC and Placebo. Therefore, the safety assessments were reported at subject level, but not per intervention.
|
|---|---|
|
Infections and infestations
Cellulitis
|
3.2%
1/31 • Number of events 1 • 6 months
|
|
Gastrointestinal disorders
Diarrhoea
|
3.2%
1/31 • Number of events 1 • 6 months
|
|
Blood and lymphatic system disorders
Anaemia
|
3.2%
1/31 • Number of events 2 • 6 months
|
|
Investigations
Blood culture positive
|
3.2%
1/31 • Number of events 1 • 6 months
|
Other adverse events
| Measure |
All Participants ("Topical Beremagene Geperpavec (B-VEC)", and "Placebo")
n=31 participants at risk
Each subject provided one pair of primary target wounds, with one wound from each pair randomized to be treated with B-VEC and the other wound with placebo. Due to the 'split-person'/intrasubject design, each subject received both B-VEC and Placebo. Therefore, the safety assessments were reported at subject level, but not per intervention.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.7%
3/31 • Number of events 4 • 6 months
|
|
Skin and subcutaneous tissue disorders
Erythema
|
6.5%
2/31 • Number of events 2 • 6 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.5%
2/31 • Number of events 2 • 6 months
|
|
General disorders
Chills
|
9.7%
3/31 • Number of events 3 • 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
9.7%
3/31 • Number of events 4 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.5%
2/31 • Number of events 2 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.5%
2/31 • Number of events 2 • 6 months
|
Additional Information
Dr. Hubert Chen, MD, Senior Vice President of Clinical Development
Krystal Biotech
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place