Immune Response to Yellow Fever Vaccination in Adults With Atopic Dermatitis

Atopic Dermatitis Clinical Trial

Official title:

A Study of the Systemic and Cutaneous Immune Responses to Yellow Fever Vaccination in Atopic Dermatitis Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00723489
• Other study ID #: DAIT ADVN YF08
• Secondary ID: HHSN266200400029
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 25, 2008
• Last updated: December 11, 2013
• Start date: August 2008
• Est. completion date: April 2011

Study information

• Verified date: December 2013
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The main objective of the Atopic Dermatitis and Vaccinia Immunization Network (ADVN) is to reduce the risk of the fatal reaction, eczema vaccinatum (EV), to the smallpox vaccination in those with atopic dermatitis (AD). Since vaccination with live vaccinia virus (VV) in individuals with AD increases the risk of EV, a yellow fever vaccine was chosen. The purpose of this study is to determine the immune response to a yellow fever vaccine in adults with AD.

Description:

AD is a chronic inflammatory skin disorder characterized by recurrent viral skin infections. The purpose of this study is to understand the immune response to a yellow fever vaccine in adults with AD. This study will provide substantial information about normal and defective cutaneous immunity in participants with AD in response to a live virus vaccine, which is critical for understanding the EV reaction.

An individual's participation in the study will last up to 13 weeks. Participants will be randomized into one of two arms. The first experimental arm will consist of 20 adults with AD and 20 healthy adults. They will receive one dose of YFV-17D by subcutaneous administration in the right deltoid and receive one dose of YFV-17D placebo by transcutaneous administration in the left deltoid. The second arm will consist of 20 adults with AD and 20 healthy adults. They will receive one dose of YFV-17D placebo by subcutaneous administration in the right deltoid and receive one dose of YFV-17D vaccine transcutaneously in the left deltoid.

This study will consist of 6 follow-up visits over a 35 day period after study entry.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 27 Years to 43 Years

Eligibility

Inclusion Criteria:

• Diagnosis of Atopic Dermatitis or Non-atopic control

• Born and currently residing in the United States

• Weight of at least 110 lbs at the Screening Visit

• Not previously vaccinated for YFV, tick-borne encephalitis (TBEV), Japanese encephalitis virus (JEV), or dengue fever

• Agree to use adequate contraception 30 days prior to and until their participation in the study is completed. More information on this criterion can be found in the protocol.

Exclusion Criteria:

• AD subjects with exfoliative erythroderma or lacking a minimum 10 cm diameter area of normal appearing skin on the deltoid or thigh vaccination sites

• Have a body mass index (BMI) of 30 or greater at the Screening Visit

• Known history of infection with YFV, dengue fever, TBEV, JEV, or West Nile Virus (WNV)

• A family history of severe reactions to the yellow fever vaccine

• Traveled to Africa or South America (including participants who plan to travel to these areas prior to completion of the study)

• History of egg allergy or have a positive egg allergy skin prick test that is administered at the Screening visit

• History of acute hypersensitivity reaction to any components of the yellow fever vaccine (including gelatin)

• Have latex allergy

• Have lidocaine allergy

• Are allergic or hypersensitive to TegadermTM

• Received systemic immunosuppressants within 30 days prior to receiving the vaccination

• Received systemic corticosteroids, anti inflammatory biologics (e.g., alefacept, etanercept, etc.), or calcineurin inhibitors within 30 days prior to receiving the vaccination

• Received systemic antibiotics or antivirals within 7 days of receiving the vaccination

• Received greater than 440 mcg of inhaled steroids per day within 6 months prior to receiving the vaccination

• Received Xolair (Omalizumab) within 1 year prior to receiving the vaccination

• Received immunotherapy within 30 days prior to receiving the vaccination

• Received any vaccine within 30 days prior to randomization or expected receipt 30 days after randomization

• Received topical antibiotics, antivirals, immune enhancers (e.g., imiquimod), or calcineurin inhibitors within 7 days prior to receiving the vaccination

• Received topical corticosteroids within 7 days prior to receiving the vaccination

• Received phototherapy (e.g., ultraviolet light B [UVB], psoralen plus ultraviolet light A [PUVA]) within 30 days prior to receiving the vaccination

• Acute febrile illness or active fungal, bacterial, or viral infections (subjects may be reconsidered for enrollment once the condition has resolved)

• Skin disease other than AD that might compromise the stratum corneum barrier (e.g., clinically evident ichthyosis, bullous disease, psoriasis)

• Current or past history of malignancy or of autoimmune or immunodeficiency diseases. More information on this criterion can be found in the protocol.

• Pregnant or breastfeeding

• Have an anti-nuclear antibody (ANA) titer that is equal to or greater than 1/160 at the Screening Visit

• Have a serum immunoglobulin (Ig)G, IgM, IgA, C3, or C4 level below the normal range at the Screening Visit

• Have a manual lymphocyte count that is less than 1000 lymphocytes per microliter

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema
• Yellow Fever

Intervention

Biological:
• Live Yellow Fever Vaccine (YFV-17D)

Drug:
• YFV-17D Placebo

Locations

Country	Name	City	State
United States	National Jewish Health	Denver	Colorado
United States	Oregon Health & Science University	Portland	Oregon
United States	University of California, San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralization Index (LNI): YFV-17D TC- (AD) Participants Compared to YFV-17D TC- (Non-AD) Participants	Log10 Neutralization Index (LNI) is the Log10 difference in virus titer (measurement of amount of virus) between pre-vaccination and post-vaccination. An LNI greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus.	30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)	No
Primary	Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralization Index (LNI): YFV-17D SC - (AD) Participants Compared to YFV-17D SC- (Non-AD) Participants	Log10 Neutralization Index (LNI) is the Log10 difference in virus titer (measurement of amount of virus) between pre-vaccination and post-vaccination. An LNI greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus.	30 days after YF immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after Yellow Fever immunization)	No
Primary	Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralizing Titer 50 (NT50): YFV-17D TC - (AD) Participants Compared to YFV-17D TC - (Non - AD) Participants	Neutralization titer (NT50) is the dilution of serum (antibody) that results in a 50% reduction in the amount of virus. A higher NT50 number reflects the presence of more protective antibody levels against the Yellow Fever virus. Some studies have used an NT50 titer of 1:10 or 1:20 as the minimum level to suggest that a person has active immunity against the Yellow Fever virus.	30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)	No
Primary	Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralizing Titer 50 (NT50): YFV-17D SC - (AD) Participants Compared to YFV-17D SC - (Non-AD) Participants	Neutralization titer (NT50) is the dilution of serum (antibody) that results in a 50% reduction in the amount of virus. A higher NT50 number reflects the presence of more protective antibody levels against the Yellow Fever virus. Some studies have used an NT50 titer of 1:10 or 1:20 as the minimum level to suggest that a person has active immunity against the Yellow Fever virus.	30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)	No
Secondary	Comparison of Count of Seroconverters: YFV-17D TC- (AD) Participants Compared to YFV-17D TC - (Non-AD) Participants	Seroconversion is defined as a Log10 Neutralization Index (LNI) of 0.7 or higher. A value greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus.	Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35)	No
Secondary	Comparison of Count of Seroconverters: YFV-17D SC - (AD) Participants Compared to YFV-17D SC - (Non-AD) Participants	Seroconversion is defined as a Log10 Neutralization Index (LNI) of 0.7 or higher. A value greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus.	Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35)	No
Secondary	Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive, CD4 Positive T-cells, YFV-17D SC - (AD) Compared to YFV-17D SC - (Non- AD) Participants	Comparison by designated reporting groups: the Log10 transformed lymphocyte count of CD4 Positive T-cells expressing IFN-gamma and TNF-alpha in every 10^6 CD4 Positive T-cells on Day 30 (acceptable blood draw window: Day 28 - 35).	Day 30 (Day 28-35)	No
Secondary	Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive , CD4 Positive T-cells, YFV-17D TC - (AD) Compared to YFV-17D TC - (Non-AD) Participants	Comparison by designated reporting groups: the Log10 transformed count of CD4 Positive T-cells that express IFN-gamma and TNF-alpha in every 10^6 CD4 Positive T- Cells (Day 30). A higher count reflects a better immune response to Yellow Fever virus.	Day 30 (Day 28-35)	No
Secondary	Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive, CD8 Positive T-cells, YFV-17D SC -(AD) Compared to YFV-17D SC - (Non-AD) Participants	Comparison by designated reporting groups: the Log10 transformed lymphocyte count of CD8 Positive T-cells expressing IFN-gamma and TNF-alpha in every 10^6 CD8 Positive T-cells.	Day 30 (Day 28-35)	No
Secondary	Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive, CD8 Positive T-cells, YFV-17D TC - (AD) Compared to YFV-17D TC - (Non-AD) Participants	Comparison by designated reporting groups: the Log10 transformed count of CD8 Positive T-cells expressing IFN-gamma and TNF-alpha in every 10^6 CD8 Positive T-cells.	Day 30 (Day 28-35)	No

External Links

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