Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study
Condition: Epidermolysis Bullosa Simplex; Epidermolysis Bullosa Simplex Kobner; Weber-Cockayne Syndrome
MeSH terms: Cockayne Syndrome; Epidermolysis Bullosa; Epidermolysis Bullosa Simplex
Intervention: Sirolimus, 2%; Vehicle
Intervention MeSH terms: Sirolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 8.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: epidermolysis bullosa simplex

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