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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03016715




Registration number
NCT03016715
Ethics application status
Date submitted
9/01/2017
Date registered
10/01/2017
Date last updated
24/10/2017

Titles & IDs
Public title
Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study
Scientific 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)
Secondary ID [1] 0 0
2016-05-413
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epidermolysis Bullosa Simplex 0 0
Epidermolysis Bullosa Simplex Kobner 0 0
Weber-Cockayne Syndrome 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sirolimus 2%
Treatment: Drugs - Vehicle

Experimental: Treatment - Sirolimus, 2% topical ointment will be used during randomization

Placebo Comparator: Vehicle - A placebo topical ointment will be used during randomization.


Treatment: Drugs: Sirolimus 2%


Treatment: Drugs: Vehicle


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Change from Baseline to End of Treatment completion at 32 Week
Secondary outcome [1] 0 0
FitBit® / pedometer
Timepoint [1] 0 0
Baseline and through study treatment completion at 32-weeks]
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Child Dermatological Quality of Life Questionnaire
Timepoint [3] 0 0
Baseline through study treatment completion at 32 weeks
Secondary outcome [4] 0 0
The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Disease Severity Scale
Timepoint [4] 0 0
Baseline and through study treatment completion at 32-weeks

Eligibility
Key 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
Minimum age
5 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Premier Specialists - Sydney
Recruitment postcode(s) [1] 0 0
2217 - Sydney

Funding & Sponsors
Primary sponsor type
Other
Name
Premier Specialists, Australia
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03016715
Trial related presentations / publications
Fine JD, Bruckner-Tuderman L, Eady RA, Bauer EA, Bauer JW, Has C, Heagerty A, Hintner H, Hovnanian A, Jonkman MF, Leigh I, Marinkovich MP, Martinez AE, McGrath JA, Mellerio JE, Moss C, Murrell DF, Shimizu H, Uitto J, Woodley D, Zambruno G. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014 Jun;70(6):1103-26. doi: 10.1016/j.jaad.2014.01.903. Epub 2014 Mar 29. Review.
Fine JD, Johnson LB, Weiner M, Suchindran C. Assessment of mobility, activities and pain in different subtypes of epidermolysis bullosa. Clin Exp Dermatol. 2004 Mar;29(2):122-7.
Lane EB, McLean WH. Keratins and skin disorders. J Pathol. 2004 Nov;204(4):355-66. Review.
Castedo M, Ferri KF, Kroemer G. Mammalian target of rapamycin (mTOR): pro- and anti-apoptotic. Cell Death Differ. 2002 Feb;9(2):99-100.
Guba M, von Breitenbuch P, Steinbauer M, Koehl G, Flegel S, Hornung M, Bruns CJ, Zuelke C, Farkas S, Anthuber M, Jauch KW, Geissler EK. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med. 2002 Feb;8(2):128-35.
Fogel AL, Hill S, Teng JM. Advances in the therapeutic use of mammalian target of rapamycin (mTOR) inhibitors in dermatology. J Am Acad Dermatol. 2015 May;72(5):879-89. doi: 10.1016/j.jaad.2015.01.014. Epub 2015 Mar 11. Review.
Raught B, Gingras AC, Sonenberg N. The target of rapamycin (TOR) proteins. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7037-44. Review.
Hickerson RP, Leake D, Pho LN, Leachman SA, Kaspar RL. Rapamycin selectively inhibits expression of an inducible keratin (K6a) in human keratinocytes and improves symptoms in pachyonychia congenita patients. J Dermatol Sci. 2009 Nov;56(2):82-8. doi: 10.1016/j.jdermsci.2009.07.008. Epub 2009 Aug 21.
Riskowski JL, Hagedorn TJ, Hannan MT. Measures of foot function, foot health, and foot pain: American Academy of Orthopedic Surgeons Lower Limb Outcomes Assessment: Foot and Ankle Module (AAOS-FAM), Bristol Foot Score (BFS), Revised Foot Function Index (FFI-R), Foot Health Status Questionnaire (FHSQ), Manchester Foot Pain and Disability Index (MFPDI), Podiatric Health Questionnaire (PHQ), and Rowan Foot Pain Assessment (ROFPAQ). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S229-39. doi: 10.1002/acr.20554. Review.
Loh CC, Kim J, Su JC, Daniel BS, Venugopal SS, Rhodes LM, Intong LR, Law MG, Murrell DF. Development, reliability, and validity of a novel Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI). J Am Acad Dermatol. 2014 Jan;70(1):89-97.e1-13. doi: 10.1016/j.jaad.2013.09.041.
Venugopal SS, Yan W, Frew JW, Cohn HI, Rhodes LM, Tran K, Melbourne W, Nelson JA, Sturm M, Fogarty J, Marinkovich MP, Igawa S, Ishida-Yamamoto A, Murrell DF. A phase II randomized vehicle-controlled trial of intradermal allogeneic fibroblasts for recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol. 2013 Dec;69(6):898-908.e7. doi: 10.1016/j.jaad.2013.08.014. Epub 2013 Sep 24.
Frew JW, Martin LK, Nijsten T, Murrell DF. Quality of life evaluation in epidermolysis bullosa (EB) through the development of the QOLEB questionnaire: an EB-specific quality of life instrument. Br J Dermatol. 2009 Dec;161(6):1323-30. doi: 10.1111/j.1365-2133.2009.09347.x. Epub 2009 Jun 11. Erratum in: Br J Dermatol. 2010 Mar;162(3):701.
Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of pruritus. Br J Dermatol. 2010 Mar;162(3):587-93. doi: 10.1111/j.1365-2133.2009.09586.x. Epub 2009 Dec 1.
Storm FA, Heller BW, Mazzà C. Step detection and activity recognition accuracy of seven physical activity monitors. PLoS One. 2015 Mar 19;10(3):e0118723. doi: 10.1371/journal.pone.0118723. eCollection 2015.
Public notes

Contacts
Principal investigator
Name 0 0
Dedee F Murrell, MD
Address 0 0
University of New South Wales
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Dedee F Murrell, MD
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
d.murrell@unsw.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03016715