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

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

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.

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.

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.