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Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03016715
Recruitment Status : Recruiting
First Posted : January 10, 2017
Last Update Posted : October 24, 2017
Information provided by (Responsible Party):
Premier Specialists, Australia

Tracking Information
First Submitted Date  ICMJE January 9, 2017
First Posted Date  ICMJE January 10, 2017
Last Update Posted Date October 24, 2017
Study Start Date  ICMJE May 2016
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 9, 2017)
Foot Health Status Questionnaire [ Time Frame: Change from Baseline to End of Treatment completion at 32 Week ]
Foot function utilizing the validated Foot Health Status Questionnaire (FHSQ) as a change from baseline to the end of each treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03016715 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2017)
  • FitBit® / pedometer [ Time Frame: Baseline and through study treatment completion at 32-weeks] ]
  • Plantar defect size using 3D Photography [ Time Frame: Change in total defect area from Baseline, clinical visits at Week 4, Week 12, Week 16, Week 28, through study treatment completion at 32-weeks ]
    Plantar defect size measurements using 3D photography (% change in total defect area) from baseline to the end of each treatment.
  • Child Dermatological Quality of Life Questionnaire [ Time Frame: Baseline through study treatment completion at 32 weeks ]
  • The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Disease Severity Scale [ Time Frame: Baseline and through study treatment completion at 32-weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study
Official Title  ICMJE A Prospective, Double-Blind, Cross-Over, Pilot Study to Assess Safety and Efficacy of Topical Sirolimus 2% in the Treatment of Plantar Blistering in Patients With Epidermolysis Bullous Simplex (EBS)
Brief 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.
Detailed Description

The proposed 40 week pilot study being conducted is a prospective, double-blind, randomized, placebo-controlled crossover study. Participants will be assigned to treat both feet with either topical sirolimus, 2% cream daily or placebo (vehicle-control) for 12 weeks, followed by a 4 week washout period, then re-treatment to both feet will occur by the cross-over intervention.

These studies will exploit the naturally occurring transcriptional regulation of keratin sequences, the known gene aberration causing EB simplex, and assess the potential for mTOR pathway inhibition in treatment of the patient's plantar lesions. The objective of this study is to assess (1) the safety of topical rapamycin for plantar lesions for the treatment of EB simplex, and 2) test if topical rapamycin to improves the clinical severity of lesional skin, including pain and itch, in subjects with EB simplex at the end of treatment versus baseline and compared to an intrasubject placebo treated control. Wound size measurement, quality of life evaluation will be assessed using epidermolysis bullosa (QOLEB), and EB disease activity and Scarring Index (EBDASI). With the results of this pilot study, physicians would be able to transition from supportive care (the current state of the art for EB simplex) to targeted molecular therapeutics, leading to improved mobility and quality of life for patients with EB simplex.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Epidermolysis Bullosa Simplex
  • Epidermolysis Bullosa Simplex Kobner
  • Weber-Cockayne Syndrome
Intervention  ICMJE
  • Drug: Sirolimus 2%
  • Drug: Vehicle
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: Treatment
    Sirolimus, 2% topical ointment will be used during randomization
    Intervention: Drug: Sirolimus 2%
  • Placebo Comparator: Vehicle
    A placebo topical ointment will be used during randomization.
    Intervention: Drug: Vehicle
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 9, 2017)
Original Estimated Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 5-18 yo
  • Be male or female with a diagnosis of EBS
  • Minimum EBDASI feet activity score of 2/10
  • Age - 5 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dedee F Murrell, MD
Contact: Charmaine Peras
Listed Location Countries  ICMJE Australia
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03016715
Other Study ID Numbers  ICMJE 2016-05-413
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Premier Specialists, Australia
Study Sponsor  ICMJE Premier Specialists, Australia
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Dedee F Murrell, MD University of New South Wales
PRS Account Premier Specialists, Australia
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP