Clinical trial NCT00723489: Immune Response to Yellow Fever Vaccination in Adults With Atopic Dermatitis
Official title: A Study of the Systemic and Cutaneous Immune Responses to Yellow Fever Vaccination in Atopic Dermatitis Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Atopic Dermatitis
Keywords: Yellow Fever Vaccine
Scarification Method
Atopic Dermatitis
IgG antibodies
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2008-07-28
Enrollment: 82
Sex: ALL
Minimum age (years): 27
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)
measure: 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
timeFrame: 30 days after YF immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after Yellow Fever immunization)
measure: 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
timeFrame: 30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)
measure: 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
timeFrame: 30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)
Secondary outcomes:
measure: Comparison of Count of Seroconverters: YFV-17D TC- (AD) Participants Compared to YFV-17D TC - (Non-AD) Participants
timeFrame: Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35)
measure: Comparison of Count of Seroconverters: YFV-17D SC - (AD) Participants Compared to YFV-17D SC - (Non-AD) Participants
timeFrame: Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35)
measure: 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
timeFrame: Day 30 (Day 28-35)
measure: 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
timeFrame: Day 30 (Day 28-35)
measure: 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
timeFrame: Day 30 (Day 28-35)
measure: 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
timeFrame: Day 30 (Day 28-35)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Jon Hanifin, M.D.
role: STUDY_CHAIR
affiliation: Oregon Health and Science University
name: Mark Slifka, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Oregon Health and Science University
name: Eric Simpson, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Jewish Health
name: Henry Milgrom, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Richard Gallo, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Slifka MK, Leung DY, Hammarlund E, Raue HP, Simpson EL, Tofte S, Baig-Lewis S, David G, Lynn H, Woolson R, Hata T, Milgrom H, Hanifin J. Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis. J Allergy Clin Immunol. 2014 Feb;133(2):439-47. doi: 10.1016/j.jaci.2013.10.037. Epub 2013 Dec 10.