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

NCT ID: NCT03016715

Last Updated: 2017-10-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

8 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

: 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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Epidermolysis Bullosa Simplex Epidermolysis Bullosa Simplex Kobner Weber-Cockayne Syndrome

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Epidermolysis bullosa simplex

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment

Sirolimus, 2% topical ointment will be used during randomization

Group Type EXPERIMENTAL

Sirolimus 2%

Intervention Type DRUG

Vehicle

A placebo topical ointment will be used during randomization.

Group Type PLACEBO_COMPARATOR

Vehicle

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Sirolimus 2%

Intervention Type DRUG

Vehicle

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Placebo

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Premier Specialists, Australia

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Dedee F Murrell, MD

Role: STUDY_CHAIR

University of New South Wales

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Premier Specialists

Sydney, New South Wales, Australia

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Australia

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Dedee F Murrell, MD

Role: CONTACT

Email: [email protected]

Charmaine Peras

Role: CONTACT

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Charmaine Peras

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 24690439 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14987264 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 15495218 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11840159 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11821896 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25769191 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11416184 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19699613 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22588747 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24355263 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24075228 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19681875 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19995367 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25789630 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2016-05-413

Identifier Type: -

Identifier Source: org_study_id