Trial Outcomes & Findings for Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study (NCT NCT02960997)
NCT ID: NCT02960997
Last Updated: 2022-03-09
Results Overview
Foot function was assessed utilizing the validated Foot Health Status Questionnaire (FHSQ). Low Score (0) means severely limited in performing a broad range of physical activities. High Score (100) means can perform all desired physical activities. Data are reported per intervention.
COMPLETED
PHASE2
8 participants
Week 0 and week 12 of the respective treatment period
2022-03-09
Participant Flow
Participant milestones
| Measure |
Sirolimus, Then Placebo
Participants will receive Sirolimus, 2% topical ointment for 12 weeks followed by placebo to match sirolimus for 12 weeks.
|
Placebo, Then Sirolimus
Participants will receive placebo to match sirolimus for 12 weeks followed by Sirolimus, 2% topical ointment for 12 weeks.
|
|---|---|---|
|
First Intervention, 12 Weeks
STARTED
|
4
|
4
|
|
First Intervention, 12 Weeks
COMPLETED
|
4
|
4
|
|
First Intervention, 12 Weeks
NOT COMPLETED
|
0
|
0
|
|
Washout Period, 4 Weeks
STARTED
|
4
|
4
|
|
Washout Period, 4 Weeks
COMPLETED
|
4
|
4
|
|
Washout Period, 4 Weeks
NOT COMPLETED
|
0
|
0
|
|
Second Treatment, 12 Weeks
STARTED
|
4
|
4
|
|
Second Treatment, 12 Weeks
COMPLETED
|
4
|
4
|
|
Second Treatment, 12 Weeks
NOT COMPLETED
|
0
|
0
|
|
Follow-up Period, 4 Weeks
STARTED
|
4
|
4
|
|
Follow-up Period, 4 Weeks
COMPLETED
|
4
|
4
|
|
Follow-up Period, 4 Weeks
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study
Baseline characteristics by cohort
| Measure |
Sirolimus, Then Placebo
n=4 Participants
Participants will receive Sirolimus, 2% topical ointment for 12 weeks followed by placebo to match sirolimus for 12 weeks.
|
Placebo, Then Sirolimus
n=4 Participants
Participants will receive placebo to match sirolimus for 12 weeks followed by Sirolimus, 2% topical ointment for 12 weeks.
|
Total
n=8 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Foot Health Status Questionnaire, Foot Function
|
51.6 score on a scale
STANDARD_DEVIATION 11.16 • n=5 Participants
|
51.6 score on a scale
STANDARD_DEVIATION 20.90 • n=7 Participants
|
51.6 score on a scale
STANDARD_DEVIATION 16.76 • n=5 Participants
|
|
Foot Health Status Questionnaire, Physical Activity
|
63.9 score on a scale
STANDARD_DEVIATION 25.00 • n=5 Participants
|
54.2 score on a scale
STANDARD_DEVIATION 22.35 • n=7 Participants
|
59.0 score on a scale
STANDARD_DEVIATION 24.21 • n=5 Participants
|
|
Child Dermatological Quality of Life Questionnaire
|
18.0 score on a scale
STANDARD_DEVIATION 10.17 • n=5 Participants
|
17.3 score on a scale
STANDARD_DEVIATION 4.60 • n=7 Participants
|
17.6 score on a scale
STANDARD_DEVIATION 7.90 • n=5 Participants
|
|
Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Disease Severity Scale
|
2.8 score on a scale
STANDARD_DEVIATION 0.43 • n=5 Participants
|
3.5 score on a scale
STANDARD_DEVIATION 0.87 • n=7 Participants
|
3.1 score on a scale
STANDARD_DEVIATION 0.78 • n=5 Participants
|
|
5-D Pruritus Score
|
15.0 score on a scale
STANDARD_DEVIATION 1.87 • n=5 Participants
|
11.0 score on a scale
STANDARD_DEVIATION 2.35 • n=7 Participants
|
13.0 score on a scale
STANDARD_DEVIATION 2.92 • n=5 Participants
|
PRIMARY outcome
Timeframe: Week 0 and week 12 of the respective treatment periodFoot function was assessed utilizing the validated Foot Health Status Questionnaire (FHSQ). Low Score (0) means severely limited in performing a broad range of physical activities. High Score (100) means can perform all desired physical activities. Data are reported per intervention.
Outcome measures
| Measure |
Sirolimus
n=8 Participants
Sirolimus, 2% topical ointment for 12 weeks
|
Placebo
n=8 Participants
Placebo to match sirolimus for 12 weeks
|
|---|---|---|
|
Foot Health Status Questionnaire, Foot Function Domain Score
Week 0
|
61.7 score on a scale
Standard Deviation 26.48
|
49.3 score on a scale
Standard Deviation 20.83
|
|
Foot Health Status Questionnaire, Foot Function Domain Score
Week 12
|
60.2 score on a scale
Standard Deviation 23.37
|
56.3 score on a scale
Standard Deviation 24.09
|
PRIMARY outcome
Timeframe: Week 0 and week 12 of the respective treatment periodPhysical Activity was assessed utilizing the validated Foot Health Status Questionnaire (FHSQ). Low Score (0) means severely limited in performing a broad range of physical activities. High Score (100) means can perform all desired physical activities. Data are reported per intervention.
Outcome measures
| Measure |
Sirolimus
n=8 Participants
Sirolimus, 2% topical ointment for 12 weeks
|
Placebo
n=8 Participants
Placebo to match sirolimus for 12 weeks
|
|---|---|---|
|
Foot Health Status Questionnaire, Physical Activity Domain Score
Week 0
|
69.4 score on a scale
Standard Deviation 24.37
|
54.2 score on a scale
Standard Deviation 21.65
|
|
Foot Health Status Questionnaire, Physical Activity Domain Score
Week 12
|
70.8 score on a scale
Standard Deviation 20.37
|
61.8 score on a scale
Standard Deviation 24.91
|
PRIMARY outcome
Timeframe: Week 12Population: Trough concentration of sirolimus was collected during Sirolimus treatment only, so the Placebo group is not presented in this outcome measure.
Trough measurements were taken prior to topical sirolimus administration at the week 12 study visit.
Outcome measures
| Measure |
Sirolimus
n=8 Participants
Sirolimus, 2% topical ointment for 12 weeks
|
Placebo
Placebo to match sirolimus for 12 weeks
|
|---|---|---|
|
Trough Concentration of Sirolimus
|
NA ng/mL
Standard Deviation NA
All measurements were below the lower limit of quantitation (\<2 ng/mL).
|
—
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: One participant had no Fitbit data during placebo treatment and is excluded from the analysis. Three participants lost their Fitbit devices for week 12 reporting during sirolimus treatment; their data through week 8 are included in the analysis.
Average number of steps walked per day from baseline to the end of each treatment.
Outcome measures
| Measure |
Sirolimus
n=8 Participants
Sirolimus, 2% topical ointment for 12 weeks
|
Placebo
n=7 Participants
Placebo to match sirolimus for 12 weeks
|
|---|---|---|
|
Average Steps Per Day Assessed by FitBit® / Pedometer
|
6624 steps
Standard Deviation 1847
|
7130 steps
Standard Deviation 3025
|
SECONDARY outcome
Timeframe: Week 0 and week 12 of the respective treatment periodQuality of Life-Epidermolysis Bullosa (QOLEB) Questionnaire specifically designed for people with EB. The QOLEB can be used to identify everyday life occurrences negatively affected by EB. It assesses change in quality of life over time, an important measure when assessing the success of new treatments for EB. Scores from 0 to 51, with higher scores indicate greater impact of EB on quality of life. Data are reported per intervention.
Outcome measures
| Measure |
Sirolimus
n=8 Participants
Sirolimus, 2% topical ointment for 12 weeks
|
Placebo
n=8 Participants
Placebo to match sirolimus for 12 weeks
|
|---|---|---|
|
Child Dermatological Quality of Life Questionnaire Score
Week 0
|
14.1 score on a scale
Standard Deviation 9.37
|
6.6 score on a scale
Standard Deviation 8.79
|
|
Child Dermatological Quality of Life Questionnaire Score
Week 12
|
14.5 score on a scale
Standard Deviation 10.14
|
13.3 score on a scale
Standard Deviation 9.32
|
SECONDARY outcome
Timeframe: Week 0 and week 12 of the respective treatment periodThe EBDASI is a validated scoring system that objectively quantifies the severity of EB affecting the entire body. It has been designed to evaluate the response to new therapies for the treatment of EB. Scores range from 0 (absent of EB) to 10 (entire area involved). Data are reported per intervention.
Outcome measures
| Measure |
Sirolimus
n=8 Participants
Sirolimus, 2% topical ointment for 12 weeks
|
Placebo
n=8 Participants
Placebo to match sirolimus for 12 weeks
|
|---|---|---|
|
Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Disease Severity Scale Score
Week 0
|
2.6 score on a scale
Standard Deviation 1.32
|
3.5 score on a scale
Standard Deviation 1.22
|
|
Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Disease Severity Scale Score
Week 12
|
2.9 score on a scale
Standard Deviation 1.54
|
2.5 score on a scale
Standard Deviation 1.41
|
SECONDARY outcome
Timeframe: Week 0 and week 12 of the respective treatment periodThe 5-D Pruritus Scale is a 1-page, 5-question tool used in clinical trials to assess 5 dimensions of background itch: degree, duration, direction, disability, and distribution. Each question corresponds to 1 of the 5 dimensions of itch; participants were to rate their symptoms over the preceding 2-week period on a 1 to 5 scale, with 5 being the most affected. After the summation of individual score, the total score ranges from 5 (least affected) to 25 (most affected). Data are reported per intervention.
Outcome measures
| Measure |
Sirolimus
n=8 Participants
Sirolimus, 2% topical ointment for 12 weeks
|
Placebo
n=8 Participants
Placebo to match sirolimus for 12 weeks
|
|---|---|---|
|
5-D Pruritus Scale Score
Week 0
|
12.8 score on a scale
Standard Deviation 3.03
|
11.5 score on a scale
Standard Deviation 1.87
|
|
5-D Pruritus Scale Score
Week 12
|
12.5 score on a scale
Standard Deviation 3.46
|
11.8 score on a scale
Standard Deviation 3.80
|
SECONDARY outcome
Timeframe: Baseline, week 12Population: Data were not collected for this outcome measure.
Plantar defect size measurements using 3D photography (% change in total defect area).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, week 12Population: Data were not collected for this outcome measure.
Foot plantar pressure measurements before and after treatment using the Podotech Elftman Foot Scanner.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, week 12Population: Data were not collected for this outcome measure
Molecular biology study of skin biopsies assayed for mTOR pathway inhibition (e.g. determination of phosphoprotein inhibition included ribosomal protein S6, S6 kinase and/or eIF-4E binding protein).
Outcome measures
Outcome data not reported
Adverse Events
Sirolimus
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sirolimus
n=8 participants at risk
Sirolimus, 2% topical ointment for 12 weeks
|
Placebo
n=8 participants at risk
Placebo to match sirolimus for 12 weeks
|
|---|---|---|
|
Immune system disorders
Allergic Reaction to antiobiotic (sulfamethoxole)
|
0.00%
0/8 • 32 weeks
|
12.5%
1/8 • 32 weeks
|
|
Skin and subcutaneous tissue disorders
Burning sensation on feet
|
12.5%
1/8 • 32 weeks
|
0.00%
0/8 • 32 weeks
|
|
Infections and infestations
Common cold
|
0.00%
0/8 • 32 weeks
|
37.5%
3/8 • 32 weeks
|
|
General disorders
Cough
|
0.00%
0/8 • 32 weeks
|
25.0%
2/8 • 32 weeks
|
|
Infections and infestations
Ear infection
|
25.0%
2/8 • 32 weeks
|
0.00%
0/8 • 32 weeks
|
|
General disorders
Feet pain
|
12.5%
1/8 • 32 weeks
|
12.5%
1/8 • 32 weeks
|
|
Injury, poisoning and procedural complications
Food poisioning
|
0.00%
0/8 • 32 weeks
|
12.5%
1/8 • 32 weeks
|
|
Infections and infestations
High fever
|
12.5%
1/8 • 32 weeks
|
0.00%
0/8 • 32 weeks
|
|
General disorders
Increased foot pain
|
0.00%
0/8 • 32 weeks
|
25.0%
2/8 • 32 weeks
|
|
Infections and infestations
Leg infected lesion
|
12.5%
1/8 • 32 weeks
|
0.00%
0/8 • 32 weeks
|
|
Gastrointestinal disorders
Loose stool
|
0.00%
0/8 • 32 weeks
|
12.5%
1/8 • 32 weeks
|
|
Renal and urinary disorders
Painful urination
|
12.5%
1/8 • 32 weeks
|
0.00%
0/8 • 32 weeks
|
|
Injury, poisoning and procedural complications
Right and left leg abrasion
|
0.00%
0/8 • 32 weeks
|
12.5%
1/8 • 32 weeks
|
|
Infections and infestations
Right footstaph infection
|
0.00%
0/8 • 32 weeks
|
12.5%
1/8 • 32 weeks
|
|
Injury, poisoning and procedural complications
Right thigh abrasion
|
0.00%
0/8 • 32 weeks
|
12.5%
1/8 • 32 weeks
|
|
Immune system disorders
Seasonal allergies
|
12.5%
1/8 • 32 weeks
|
0.00%
0/8 • 32 weeks
|
|
Infections and infestations
Sinusitis
|
0.00%
0/8 • 32 weeks
|
12.5%
1/8 • 32 weeks
|
|
Gastrointestinal disorders
Upset stomach
|
0.00%
0/8 • 32 weeks
|
12.5%
1/8 • 32 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/8 • 32 weeks
|
12.5%
1/8 • 32 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place