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Trial details imported from ClinicalTrials.gov

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

2016-05-413

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Epidermolysis Bullosa Simplex

Epidermolysis Bullosa Simplex Kobner

Weber-Cockayne Syndrome

Condition category

Condition code

Neurological

Neurodegenerative diseases

Human Genetics and Inherited Disorders

Other human genetics and inherited disorders

Skin

Dermatological conditions

Skin

Other skin conditions

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

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

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

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Foot Health Status Questionnaire

Timepoint [1]

Change from Baseline to End of Treatment completion at 32 Week

Secondary outcome [1]

FitBit® / pedometer

Timepoint [1]

Baseline and through study treatment completion at 32-weeks]

Secondary outcome [2]

Plantar defect size using 3D Photography

Timepoint [2]

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]

Child Dermatological Quality of Life Questionnaire

Timepoint [3]

Baseline through study treatment completion at 32 weeks

Secondary outcome [4]

The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Disease Severity Scale

Timepoint [4]

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

Sex

Both males and females

Can healthy volunteers participate?

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

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

1/05/2016

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]

Premier Specialists - Sydney

Recruitment postcode(s) [1]

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/study/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.
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. doi: 10.1111/j.1365-2230.2004.01428.x.
Lane EB, McLean WH. Keratins and skin disorders. J Pathol. 2004 Nov;204(4):355-66. doi: 10.1002/path.1643.
Castedo M, Ferri KF, Kroemer G. Mammalian target of rapamycin (mTOR): pro- and anti-apoptotic. Cell Death Differ. 2002 Feb;9(2):99-100. doi: 10.1038/sj.cdd.4400978. No abstract available.
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. doi: 10.1038/nm0202-128.
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.
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. doi: 10.1073/pnas.121145898.
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(0 11):S229-39. doi: 10.1002/acr.20554. No abstract available.
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, Mazza 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

Dedee F Murrell, MD

Address

University of New South Wales

Country

Phone

Fax

Contact person for public queries

Name

Dedee F Murrell, MD

Address

Country

Phone

Fax

d.murrell@unsw.edu.au

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT03016715

Trial Review

Registering a new trial?

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