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

NCT03016715 | Unknown Phase 2

• 1 other identifier: 2016-05-413
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Epidermolysis bullosa simplex

Outcome Measures

Primary Outcomes (1)

• 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.

  Change from Baseline to End of Treatment completion at 32 Week

Secondary Outcomes (4)

• FitBit® / pedometer

  Baseline and through study treatment completion at 32-weeks]

• Plantar defect size using 3D Photography

  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

  Baseline through study treatment completion at 32 weeks

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

  Baseline and through study treatment completion at 32-weeks

Study Arms (2)

Treatment

EXPERIMENTAL

Sirolimus, 2% topical ointment will be used during randomization

Drug: Sirolimus 2%

Vehicle

PLACEBO COMPARATOR

A placebo topical ointment will be used during randomization.

Drug: Vehicle

Interventions

Sirolimus 2% DRUG

Treatment

Vehicle DRUG

Also known as: Placebo

Vehicle

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Premier Specialists, Australia: lead

Study Sites (1)

Premier Specialists

Sydney, New South Wales, 2217, Australia

RECRUITING

Related Publications (14)

• 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.

  PMID: 24690439 BACKGROUND

• 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.

  PMID: 14987264 BACKGROUND

• Lane EB, McLean WH. Keratins and skin disorders. J Pathol. 2004 Nov;204(4):355-66. doi: 10.1002/path.1643.

  PMID: 15495218 BACKGROUND

• 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.

  PMID: 11840159 BACKGROUND

• 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.

  PMID: 11821896 BACKGROUND

• 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.

  PMID: 25769191 BACKGROUND

• 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.

  PMID: 11416184 BACKGROUND

• 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.

  PMID: 19699613 BACKGROUND

• 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.

  PMID: 22588747 BACKGROUND

• 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.

  PMID: 24355263 BACKGROUND

• 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.

  PMID: 24075228 BACKGROUND

• 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.

  PMID: 19681875 BACKGROUND

• 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.

  PMID: 19995367 BACKGROUND

• 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.

  PMID: 25789630 BACKGROUND

MeSH Terms

Conditions

Epidermolysis Bullosa Simplex

Condition Hierarchy (Ancestors)

Epidermolysis Bullosa; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vesiculobullous

Study Officials

• Dedee F Murrell, MD

  University of New South Wales

  STUDY CHAIR

Central Study Contacts

Dedee F Murrell, MD

CONTACT

d.murrell@unsw.edu.au

Charmaine Peras

CONTACT

premierspecnurse@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2017
• First Posted: January 10, 2017
• Study Start: May 1, 2016
• Primary Completion: June 1, 2019
• Last Updated: October 24, 2017

Record last verified: 2017-10

Locations

AU (1)