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

Primary Purpose

Epidermolysis Bullosa Simplex, Epidermolysis Bullosa Simplex Kobner, Weber-Cockayne Syndrome

Status
Unknown status
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Sirolimus 2%
Vehicle
Sponsored by
Premier Specialists, Australia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epidermolysis Bullosa Simplex focused on measuring Epidermolysis bullosa simplex

Eligibility Criteria

5 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Premier SpecialistsRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment

Vehicle

Arm Description

Sirolimus, 2% topical ointment will be used during randomization

A placebo topical ointment will be used during randomization.

Outcomes

Primary Outcome Measures

Foot Health Status Questionnaire
Foot function utilizing the validated Foot Health Status Questionnaire (FHSQ) as a change from baseline to the end of each treatment.

Secondary Outcome Measures

FitBit® / pedometer
Plantar defect size using 3D Photography
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
The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Disease Severity Scale

Full Information

First Posted
January 9, 2017
Last Updated
October 22, 2017
Sponsor
Premier Specialists, Australia
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1. Study Identification

Unique Protocol Identification Number
NCT03016715
Brief Title
Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Unknown status
Study Start Date
May 2016 (undefined)
Primary Completion Date
June 2019 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Premier Specialists, Australia

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epidermolysis Bullosa Simplex, Epidermolysis Bullosa Simplex Kobner, Weber-Cockayne Syndrome
Keywords
Epidermolysis bullosa simplex

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
8 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
Sirolimus, 2% topical ointment will be used during randomization
Arm Title
Vehicle
Arm Type
Placebo Comparator
Arm Description
A placebo topical ointment will be used during randomization.
Intervention Type
Drug
Intervention Name(s)
Sirolimus 2%
Intervention Type
Drug
Intervention Name(s)
Vehicle
Other Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Foot Health Status Questionnaire
Description
Foot function utilizing the validated Foot Health Status Questionnaire (FHSQ) as a change from baseline to the end of each treatment.
Time Frame
Change from Baseline to End of Treatment completion at 32 Week
Secondary Outcome Measure Information:
Title
FitBit® / pedometer
Time Frame
Baseline and through study treatment completion at 32-weeks]
Title
Plantar defect size using 3D Photography
Description
Plantar defect size measurements using 3D photography (% change in total defect area) from baseline to the end of each treatment.
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
Title
Child Dermatological Quality of Life Questionnaire
Time Frame
Baseline through study treatment completion at 32 weeks
Title
The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Disease Severity Scale
Time Frame
Baseline and through study treatment completion at 32-weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dedee F Murrell, MD
Email
d.murrell@unsw.edu.au
First Name & Middle Initial & Last Name or Official Title & Degree
Charmaine Peras
Email
premierspecnurse@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dedee F Murrell, MD
Organizational Affiliation
University of New South Wales
Official's Role
Study Chair
Facility Information:
Facility Name
Premier Specialists
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charmaine Peras
Phone
61 02 9598 5800
Email
premierspecnurse@gmail.com
First Name & Middle Initial & Last Name & Degree
Dedee F Murrell, MD
First Name & Middle Initial & Last Name & Degree
Charlotte E Gollins, MBChB
First Name & Middle Initial & Last Name & Degree
Anes Yang
First Name & Middle Initial & Last Name & Degree
Melissa Radjenovic

12. IPD Sharing Statement

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

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