Phase 2
N=8
Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study
Epidermolysis Bullosa Simplex · Epidermolysis Bullosa Simplex Kobner · Weber-Cockayne Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT02960997 ↗Enrolled (actual)
8
Serious AEs
0.0%
Results posted
Jan 2020
Primary outcome: Primary: Foot Health Status Questionnaire, Foot Function Domain Score — 61.7; 49.3; 60.2; 56.3 score on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Sirolimus, 2% (Drug); Vehicle (Drug)
- Age
- Pediatric, Adult, Older Adult · 4+ yrs
- Sex
- All
- Sponsor
- Stanford University
- Primary completion
- Dec 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Foot Health Status Questionnaire, Foot Function Domain Score |
61.7; 49.3; 60.2; 56.3 | — |
| PRIMARY Foot Health Status Questionnaire, Physical Activity Domain Score |
69.4; 54.2; 70.8; 61.8 | — |
| PRIMARY Trough Concentration of Sirolimus |
NA | — |
| SECONDARY Average Steps Per Day Assessed by FitBit® / Pedometer |
6624; 7130 | — |
| SECONDARY Child Dermatological Quality of Life Questionnaire Score |
14.1; 6.6; 14.5; 13.3 | — |
| SECONDARY Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Disease Severity Scale Score |
2.6; 3.5; 2.9; 2.5 | — |
| SECONDARY 5-D Pruritus Scale Score |
12.8; 11.5; 12.5; 11.8 | — |
| SECONDARY Plantar Defect Size Using 3D Photography |
— | — |
| SECONDARY Foot Plantar Pressure Measurements |
— | — |
| SECONDARY Change in mTOR Pathway Inhibition |
— | — |
Summary
Epidermolysis bullosa (EB) simplex is a rare orphan disease caused by a mutation in DNA leading to abnormal dominant keratins in the skin. Patients with EB simplex develop lifelong painful thick soles on their feet, and current standard of care is supportive. This pilot study will target the dominant mutant keratin proteins in the skin to ameliorate the severity of EB simplex. The purpose is to improve the function of EB simplex feet with an application of topical sirolimus, 2%. The investigators plan on inhibiting the mTOR pathway to down regulate the translation of defective keratin proteins and work through anti proliferative pathways.
Eligibility Criteria
Inclusion Criteria
Subjects must:
- Be capable of understanding the purpose and risks of the study and sign a written Informed Consent Form (ICF); Legally authorized representative of subjects willing and able to give consent for children 4-18 yo.
- Be male or female with a diagnosis of EBS
- Minimum EBDASI feet activity score of 2/10
- Age - 4 years or older
- Ability to complete 12 study visits within a 40-week period, each for approximately 30-60 minutes.
- Anticipated life expectancy ≥52 weeks.
- Males and females of childbearing potential should be using an effective means of contraception.
- Laboratory values within the range of normal for the participating institution unless the PI feels they are not clinically relevant
- Be able to comply with all study requirements
Exclusion Criteria
- Allergy to sirolimus or components of the vehicle ointment
- Pregnancy, breast feeding
- Prior history of liver disease
- Serious known concurrent medical illness or infection, which could potentially present a safety risk and/or prevent compliance with the requirements of the treatment program.
- Known immunodeficiency virus or syndrome including those with:
- Acquired Immunodeficiency Syndrome (AIDS)
- Human Immunodeficiency Virus (HIV)
- Hepatitis B
- Prior history of grafting surgeries or other surgeries in the dermatologic treatment area
- History of significant condition in the dermatologic treatment area such as trauma, which could impair evaluation for the treatment of EBS or non-healing chronic wound.
- Use of other investigational drugs within 30 days of the screening visit and/or has not recovered from any side effects of prior investigational drugs or procedure in the affected area (e.g., a biopsy).
- Use of acitretin within the last 1 month
- Use of Roaccutane within last 3 months
- Botox injections to the feet within the last 6 months.
- Participant is planning extra physical activities within the next 3 months.
- Amputated foot
Data sourced from ClinicalTrials.gov (NCT02960997). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.