A Phase II Study on Immunogenicity and Safety of MVA-BN® (IMVAMUNE™) Smallpox Vaccine in Subjects With Atopic Dermatitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the immunogenicity and safety of an investigational smallpox vaccine in subjects with atopic dermatitis to healthy volunteers.

Official Title
-----------------
A Multicenter, Open-label, Controlled Phase II Study to Evaluate Immunogenicity and Safety of MVA-BN® (IMVAMUNE™) Smallpox Vaccine in 18-40 Year Old Subjects With Diagnosed Atopic Dermatitis

Conditions
-----------------
Atopic Dermatitis

Intervention / Treatment
-----------------
* Biological: IMVAMUNE


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Group 1 (Healthy Participants): Subjects without present or history of any kind of atopy. Group 2 (Atopic Dermatitis Participants): Subjects with diagnosed atopic dermatitis. All study subjects: Male and female subjects between 18 and 40 years of age without history of smallpox vaccination. Women must have a negative serum pregnancy test at screening and a negative urine or serum pregnancy test within 24 hours prior to vaccination. Women of childbearing potential must have used an acceptable method of contraception for 30 days prior to the first vaccination, must agree to use an acceptable method of contraception during the study, and must not become pregnant for at least 28 days after the last vaccination. Lab values without clinically significant findings. Electrocardiogram (ECG) without clinically significant findings. Exclusion Criteria: Pregnant or breast-feeding women. Uncontrolled serious infection i.e. not responding to antimicrobial therapy. History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid replacement are not excluded. Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment. History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure. Subjects with history of skin cancer at the vaccination site are excluded. History of coronary heart disease, myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure. History of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before age 50 years. Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool: (http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof) NOTE: This criterion applies only to volunteers 20 years of age and older. History of anaphylaxis or severe allergic reaction. Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy. Administration of immunomodulatory substances.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Participants<br>Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE) | Biological: IMVAMUNE<br>* Subjects receiving two subcutaneous vaccinations<br>* Other names: MVA-BN;|
| Experimental: Atopic Dermatitis Participants<br>Vaccinia naive subjects with diagnosed Atopic Dermatitis. Diagnosed AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] <= 30), receiving two doses of MVA-BN (IMVAMUNE) | Biological: IMVAMUNE<br>* Subjects receiving two subcutaneous vaccinations<br>* Other names: MVA-BN;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Seroconversion by ELISA | Seroconversion rate based on Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available. | week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Seroconversion by ELISA | Seroconversion rate based on Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available. | within 32 weeks | 
| ELISA GMT | Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Titers below the detection limit are included with a value of '1'. | within 32 weeks | 
| Percentage of Participants With Seroconversion by PRNT | Seroconversion rate based on Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (15) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available. | within 32 weeks | 
| PRNT GMT | Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Titers below the detection limit are included with a value of '1'. | within 32 weeks | 
| ELISPOT IFN-γ Values | Number of interferon gamma (IFN-γ) secreting peripheral blood mononuclear cells (PBMC) per 10^6 PBMC in response to restimulation with MVA-BN detected by ELISPOT assay | within 6 weeks | 
| Number of Participants With SAEs | Occurrence, relationship and intensity of any serious AE (SAE) | within 32 weeks | 
| Number of Participants With Related Grade >=3 Adverse Events | Number of Participants with any Grade >=3 Adverse Event probably, possibly, or definitely related to the study vaccine. Pooled solicited (general) and unsolicited AEs. | within 29 days after vaccination | 
| Number of Participants With Solicited Local Adverse Events | Number of Participants with and Intensity of solicited local AEs (erythema, swelling and pain). Percentages based on subjects with at least one completed diary card. | within 8 days after any vaccination | 
| Number of Participants With Solicited General AEs | Number of Participants with solicited systemic/general AEs (elevated body temperature, headache, myalgia, nausea, fatigue and chills): Intensity and relationship to vaccination. Percentages based on subjects with at least one completed diary card. | within 8 days after any vaccination | 
| Number of Unsolicited Non-serious Adverse Events: Intensity | Occurrence of unsolicited non-serious AEs by Intensity | within 29 days after any vaccination | 
| Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Occurrence of unsolicited non-serious AEs by relationship to study vaccine | within 29 days after any vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Atopic dermatitis, Smallpox, Vaccination