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

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02317276
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 11
• Location: 1
• Arm: 1
• Duration (Months): 28.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Dermatitis, Atopic	Drug: Triamcinolone 0.1%	Phase 4

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Open label
• Primary Purpose: Treatment
• Official Title: A Study in Atopic Dermatitis to Determine Serum and Skin Biopsy Biomarkers in Patients Receiving Topical Corticosteroid (TCS) and Following TCS Withdrawal
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Apr 6, 2017
• Actual Study Completion Date: Apr 6, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Topical Triamcinolone 0.1% ointment will be provided for twice daily application, during treatment periods.	Drug: Triamcinolone 0.1%; Topical ointment; Other Names: Triamcinolone 0.1% ointment

Outcome Measures

Primary Outcome Measures

1. Change in Blood and Tissue Levels of Biomarkers Following Treatment of Atopic Dermatitis With Topical Corticosteroids. [Baseline to Week 8]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Dermatology	San Francisco	California	United States	94115

Sponsors and Collaborators

• University of California, San Francisco
• Genentech, Inc.

Investigators

• Principal Investigator: Sarah Arron, MD, PhD, University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 5, 2016

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02317276
• Other Study ID Numbers: GNE AD 431
• First Posted: Dec 15, 2014
• Last Update Posted: Jan 24, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate

Study Results

Participant Flow

Recruitment Details	For this study we recruited participants from UCSF Dermatology Clinic, and by posting advertisements online
Pre-assignment Detail	There was 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

Arm/Group Title	Treatment
Arm/Group Description	Topical Triamcinolone 0.1% ointment will be provided for twice daily application, during treatment periods. Triamcinolone 0.1%: Topical ointment
Period Title: Overall Study
STARTED	11
COMPLETED	5
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	Topical Triamcinolone 0.1% ointment will be provided for twice daily application, during treatment periods. Triamcinolone 0.1%: Topical ointment
Overall Participants	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32 (11)
Sex: Female, Male (Count of Participants)
Female	5 45.5%
Male	6 54.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	11 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	4 36.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 18.2%
White	4 36.4%
More than one race	1 9.1%
Unknown or Not Reported	0 0%
Eczema Area and Severity Index (EASI) (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	19.7 (6.7)
Investigator's Global Assessment (IGA) (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	3.1 (0.3)

Outcome Measures

1. Primary Outcome

Title	Change in Blood and Tissue Levels of Biomarkers Following Treatment of Atopic Dermatitis With Topical Corticosteroids.
Description	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.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

No samples were analyzed for the primary outcome measure of change in blood and tissue levels. Since the study was terminated, the blood and tissue samples were not analyzed as planned.

Arm/Group Title	Treatment
Arm/Group Description	Topical Triamcinolone 0.1% ointment will be provided for twice daily application, during treatment periods. Triamcinolone 0.1%: Topical ointment
Measure Participants	0

Adverse Events

Time Frame	Adverse events were collected for 1 year, during the duration of the study.
Arm/Group Title	Treatment
Arm/Group Description	Topical Triamcinolone 0.1% ointment will be provided for twice daily application, during treatment periods. Triamcinolone 0.1%: Topical ointment
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	0/11 (0%)

Limitations/Caveats

Due to our inability to meet the sponsor's recruitment goals, the study was terminated and no data was analyzed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.