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

October 22, 2017 updated by: Premier Specialists, Australia

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)

: 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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

8

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2217
        • Recruiting
        • Premier Specialists
        • Contact:
        • Principal Investigator:
          • Dedee F Murrell, MD
        • Sub-Investigator:
          • Charlotte E Gollins, MBChB
        • Sub-Investigator:
          • Anes Yang
        • Sub-Investigator:
          • Melissa Radjenovic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
Sirolimus, 2% topical ointment will be used during randomization
Drug: Sirolimus 2%
Placebo Comparator: Vehicle
A placebo topical ointment will be used during randomization.
Drug: Vehicle
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Change from Baseline to End of Treatment completion at 32 Week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
FitBit® / pedometer
Time Frame: Baseline and through study treatment completion at 32-weeks]
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.
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
Child Dermatological Quality of Life Questionnaire
Time Frame: Baseline through study treatment completion at 32 weeks
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
Baseline and through study treatment completion at 32-weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Premier Specialists, Australia

Investigators

  • Study Chair: Dedee F Murrell, MD, University of New South Wales

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2016

Primary Completion (Anticipated)

June 1, 2019

Study Registration Dates

First Submitted

January 9, 2017

First Submitted That Met QC Criteria

January 9, 2017

First Posted (Estimate)

January 10, 2017

Study Record Updates

Last Update Posted (Actual)

October 24, 2017

Last Update Submitted That Met QC Criteria

October 22, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-05-413

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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