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Immune Response to Yellow Fever Vaccination in Adults With Atopic Dermatitis

Primary Purpose

Atopic Dermatitis

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Live Yellow Fever Vaccine (YFV-17D)

YFV-17D Placebo

About this trial

This is an interventional basic science trial for Atopic Dermatitis focused on measuring Yellow Fever Vaccine, Scarification Method, Atopic Dermatitis, IgG antibodies

Eligibility Criteria

27 Years - 43 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

University of California, San Diego
National Jewish Health
Oregon Health & Science University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

YFV-17D (Right Deltoid)

YFV-17D (Left Deltoid)

Arm Description

Participants will be randomized within each atopic dermatitis (AD) severity subgroup or as non-atopic controls to either subcutaneous (SC) or transcutaneous (TC) vaccine administration. In this arm, participants will receive a standard vaccine dose (5.5x10^4 Plaque Forming Units) of YFV-17D administered subcutaneously in the right deltoid and placebo vaccination transcutaneously (then covered with a semi-occlusive dressing) in the left deltoid. The site pharmacist will maintain the blind and an unblinded (i.e., masked) site coordinator will administer assigned treatment: investigators, participants and assessors remain blinded to treatment assignments throughout the duration of the trial.

Participants will be randomized within each atopic dermatitis (AD) severity subgroup or as non-atopic controls to either subcutaneous (SC) or transcutaneous (TC) vaccination. In this arm, participants will receive YFV-17D vaccination (1x10^3 Plaque Forming Units) by transcutaneous administration (then covered with a semi-occlusive dressing to optimize YFV-17D absorption) in the left deltoid and placebo by subcutaneous administration in the right deltoid. The site pharmacist will maintain the blind and an unblinded (i.e., masked) site coordinator will administered treatment: investigators, participants and assessors remain blinded to treatment assignments throughout the duration of the trial.

Outcomes

Primary Outcome Measures

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.

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

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.

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

Secondary Outcome Measures

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.

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.

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).

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.

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.

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.

Full Information

NCT ID

NCT00723489

First Posted

July 25, 2008

Last Updated

December 11, 2013

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT00723489

Brief Title

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

2. Study Status

Record Verification Date

December 2013

Overall Recruitment Status

Completed

Study Start Date

August 2008 (undefined)

Primary Completion Date

April 2011 (Actual)

Study Completion Date

April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atopic Dermatitis

Keywords

Yellow Fever Vaccine, Scarification Method, Atopic Dermatitis, IgG antibodies

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

82 (Actual)

8. Arms, Groups, and Interventions

Arm Title

YFV-17D (Right Deltoid)

Arm Type

Experimental

Arm Description

Arm Title

YFV-17D (Left Deltoid)

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Live Yellow Fever Vaccine (YFV-17D)

Intervention Type

Drug

Intervention Name(s)

YFV-17D Placebo

Primary Outcome Measure Information:

Title

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

Description

Time Frame

30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)

Title

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

Description

Time Frame

30 days after YF immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after Yellow Fever immunization)

Title

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

Description

Time Frame

30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)

Title

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

Description

Time Frame

30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)

Secondary Outcome Measure Information:

Title

Comparison of Count of Seroconverters: YFV-17D TC- (AD) Participants Compared to YFV-17D TC - (Non-AD) Participants

Description

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.

Time Frame

Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35)

Title

Comparison of Count of Seroconverters: YFV-17D SC - (AD) Participants Compared to YFV-17D SC - (Non-AD) Participants

Description

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.

Time Frame

Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35)

Title

Description

Time Frame

Day 30 (Day 28-35)

Title

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

Description

Time Frame

Day 30 (Day 28-35)

Title

Description

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.

Time Frame

Day 30 (Day 28-35)

Title

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

Description

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.

Time Frame

Day 30 (Day 28-35)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

27 Years

Maximum Age & Unit of Time

43 Years

Accepts Healthy Volunteers

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

Overall Study Officials: