A Study to Determine Serum and Skin Biopsy Biomarkers in Patients Receiving Topical Corticosteroid (TCS) and Following TCS Withdrawal

Dermatitis, Atopic Clinical Trial

— GNE-AD  

Official title:

A Study in Atopic Dermatitis to Determine Serum and Skin Biopsy Biomarkers in Patients Receiving Topical Corticosteroid (TCS) and Following TCS Withdrawal

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02317276
• Other study ID #: GNE AD 431
• Status: Terminated
• Phase: Phase 4
• Start date: December 2014
• Est. completion date: April 6, 2017

Study information

• Verified date: January 2019
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the differential expression of AD biomarkers in serum, plasma, and skin biopsies from both lesional and non-lesional skin in moderate to severe AD patients in the presence of TCS and after withdrawal from TCS.

Description:

This exploratory study consists of four visits to the investigator site post screening: at Weeks 0 (baseline), 2, 6 and 8 (Figure 1). At the first visit (baseline), patients who have met the screening eligibility criteria will be started on a stable TCS regimen for a total of two weeks. At the second visit (Week 2) following two weeks of therapy on stable TCS, patients will stop TCS and blood, serum, plasma and two 6mm punch biopsies (one lesional (L) and one non-lesional (NL) skin) will be obtained. At the third visit (Week 6), after four weeks receiving no TCS, the same sample collections will be repeated and the patients will then enter a two week safety follow up. At the end of the safety follow up (last visit, Week 8) and after obtaining written informed consent by the patient, blood, serum and plasma samples mav be collected.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: April 6, 2017
• Est. primary completion date: April 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male or female patients 18-75 years of age

2. AD diagnosed by the Rajka/Hanifin criteria at the time of screening and that has been present for at least 1 year

3. History of inadequate response to a stable regimen of TCS for 1 month (in the 3 months immediately preceding the screening visit) as treatment for their AD

4. Eczema Area and Severity Index (EASI) score = 14 at the screening and baseline visits

5. Investigator's Global Assessment (IGA; 5-point) score = 3 at the screening and baseline visits

6. =10% body surface area involvement by AD

7. A washout period prior to screening for those patients who have previously received the following medications:

• Cyclosporine/Oral Steroids/Imuran/Mycophenolate Mofetil/Other systemic immunosuppressants: 4 weeks

• Phototherapy: 4 weeks

• Biologics: 5 half lives of the drug

Exclusion Criteria:

1. Evidence of other concomitant skin conditions (e.g., psoriasis or contact dermatitis)

2. Use of topical calcineurin inhibitors within 4 weeks of screening

3. Hypersensitivity to TCS or to any other ingredients contained by the emollient or TCS product used during the study

4. Evidence of active skin infection at screening or baseline visit

5. Evidence or history of active or latent infections such as tuberculosis or hepatitis C

6. Patient clinical condition is not appropriate for treatment with protocol prescribed TCS

7. Use of an investigational agent within 4 weeks prior to screening or within 5 half-lives of the investigational agent, whichever is longer

8. Use of a tanning booth/parlor within 4 weeks before the baseline visit

9. Use of any anti-histamine medication within 4 weeks before the baseline visit.

10. History of any condition (e.g. bleeding diathesis) that may predispose the patient to complications associated with the planned skin biopsy procedures

11. Known current malignancy or current evaluation for a potential malignancy, including basal or squamous cell carcinoma of the skin or carcinoma in situ

12. Other clinically significant medical disease that is uncontrolled despite treatment that is likely, in the opinion of the investigator, to impact the patient's ability to participate in the study or to impact the study pharmacodynamic (PD), or safety assessments

13. Unwillingness or inability to comply with the study protocol for any other reason.

Related Conditions & MeSH terms

• Dermatitis
• Dermatitis, Atopic

Intervention

Drug:
• Triamcinolone 0.1%
Topical ointment

Locations

Country	Name	City	State
United States	UCSF Dermatology	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (7)

Bieber T. Atopic dermatitis. N Engl J Med. 2008 Apr 3;358(14):1483-94. doi: 10.1056/NEJMra074081. — View Citation

Choy DF, Hsu DK, Seshasayee D, Fung MA, Modrusan Z, Martin F, Liu FT, Arron JR. Comparative transcriptomic analyses of atopic dermatitis and psoriasis reveal shared neutrophilic inflammation. J Allergy Clin Immunol. 2012 Dec;130(6):1335-43.e5. doi: 10.101 — View Citation

Gittler JK, Shemer A, Suárez-Fariñas M, Fuentes-Duculan J, Gulewicz KJ, Wang CQ, Mitsui H, Cardinale I, de Guzman Strong C, Krueger JG, Guttman-Yassky E. Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute — View Citation

Ring J, Alomar A, Bieber T, Deleuran M, Fink-Wagner A, Gelmetti C, Gieler U, Lipozencic J, Luger T, Oranje AP, Schäfer T, Schwennesen T, Seidenari S, Simon D, Ständer S, Stingl G, Szalai S, Szepietowski JC, Taïeb A, Werfel T, Wollenberg A, Darsow U; Europ — View Citation

Schneider L, Tilles S, Lio P, Boguniewicz M, Beck L, LeBovidge J, Novak N, Bernstein D, Blessing-Moore J, Khan D, Lang D, Nicklas R, Oppenheimer J, Portnoy J, Randolph C, Schuller D, Spector S, Tilles S, Wallace D. Atopic dermatitis: a practice parameter — View Citation

Simpson EL. Atopic dermatitis: a review of topical treatment options. Curr Med Res Opin. 2010 Mar;26(3):633-40. doi: 10.1185/03007990903512156. Review. — View Citation

Williams DL, Ozment-Skelton T, Li C. Modulation of the phosphoinositide 3-kinase signaling pathway alters host response to sepsis, inflammation, and ischemia/reperfusion injury. Shock. 2006 May;25(5):432-9. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Blood and Tissue Levels of Biomarkers Following Treatment of Atopic Dermatitis With Topical Corticosteroids.	The blood and skin biomarkers to be evaluated include but are not limited to eosinophils, Immunoglobulin E (IgE), Interleukin 13 (IL-13), Chemokine ligand 13 (CCL-13), and Chemokine ligand 17 (CCL-17). These biomarkers will be evaluated for differential gene expression and protein levels in samples obtained from atopic dermatitis patients on and off topical corticosteroid treatment.	Baseline to Week 8