Safety, Tolerability and Immune Response of IMVAMUNE (MVA-BN)Smallpox Vaccine in Patients With Atopic Disorders

Study Overview
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Brief Summary
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The purpose of this study is to gather information on the safety and immunogenicity of an investigational smallpox vaccine in populations with atopic disorders.

Official Title
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An Open-label, Controlled Phase I Pilot Study to Evaluate Safety and Immunogenicity of MVA-BN® Smallpox Vaccine in 18-40 Year Old Vaccinia-naïve Subjects With Atopic Disorders

Conditions
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Dermatitis, Atopic, Hay Fever

Intervention / Treatment
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* Biological: IMVAMUNE (MVA-BN)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects Age 18-40. Read, signed and dated informed consent. Women of childbearing potential must use an acceptable method of contraception Group 1: Healthy subjects No history of atopic dermatitis as documented in the patient file No active atopic dermatitis No other atopic disorders such as asthma or allergic rhinitis. Prick test without clinical significance IgE within normal range Group 2: Subjects with history of atopic dermatitis Group 3: Subjects with mild active atopic dermatitis - SCORAD 1 - 15. Group 4: Subjects with mild allergic rhinitis At least one active allergic rhinitis phase during last year. Exclusion Criteria: Known or suspected history of smallpox vaccination or typical vaccinia scar. Positive test result in MVA specific ELISA at screening. Positive result in HIV or HCV antibody test at screening. Surface antigen of Hepatitis B Virus (HBsAg) positive at screening. Pregnant or breast-feeding women. Positive pregnancy test at screening and/or within 24 hours prior to vaccination. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the institutional upper limit of normal. Positive urine glucose by dipstick or urine analysis. Inadequate renal function defined as a serum creatinine above the institutional upper limit of normal; urine protein >30 mg/dl or trace proteinuria (by urine analysis or dipstick); and a calculated creatinine clearance <80 ml/min. Electrocardiogram (ECG) with clinical significance. Hemoglobin <11 g/dl; White blood cells less than 2,500 and more than 11,000/mm3; Platelets less than 140,000/mm3. Uncontrolled serious infection i.e. not responding to antimicrobial therapy. History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject. History of or active autoimmune disease. 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. History or clinical manifestation of clinically significant mental illness or haematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders. Any condition which might interfere with study objectives. History of immunodeficiency. History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor. Three or more of the following risk factors: High blood pressure, high blood cholesterol, diabetes mellitus or high blood sugar, a first degree relative who had a heart condition before the age of 50, smoking cigarettes. History of chronic alcohol abuse and/or intravenous drug abuse. History of allergic reactions likely to be exacerbated by any component of the vaccine. History of anaphylaxis or severe allergic reaction. Acute disease (illness with or without a fever) at the time of enrollment. Any vaccinations within a period starting 30 days prior to administration of the vaccine and ending at study conclusion. Chronic administration of immuno-suppressant or immune-modifying drugs. Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy. Administration or planned administration of immunoglobulins and/or any blood -- Use of any investigational or non-registered drug. Blood donation 8 weeks in advance or during study participation.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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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: GP 1: healthy, no AD<br>Healthy subjects without any history of, or current signs and symptoms of atopic disease, receiving two doses IMVAMUNE (MVA-BN), subcutaneous. | Biological: IMVAMUNE (MVA-BN)<br>* 1x10E08 TCID50, subcutaneous vaccination<br>|
| Experimental: GP2: prev. allerg. rhinitis<br>Subjects having documentation of at least one allergic rhinitis event during the previous year, receiving two doses IMVAMUNE (MVA-BN), subcutaneous.. | Biological: IMVAMUNE (MVA-BN)<br>* 1x10E08 TCID50, subcutaneous vaccination<br>|
| Experimental: GP3: history of AD<br>Subjects having documentation of a history of Atopic Dermatitis, receiving two doses IMVAMUNE (MVA-BN), subcutaneous.. | Biological: IMVAMUNE (MVA-BN)<br>* 1x10E08 TCID50, subcutaneous vaccination<br>|
| Experimental: GP4: active AD<br>Subjects presenting active Atopic Dermatitis and having an individual SCORAD value between 1 and 15, receiving two doses IMVAMUNE (MVA-BN), subcutaneous. | Biological: IMVAMUNE (MVA-BN)<br>* 1x10E08 TCID50, subcutaneous vaccination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence, relationship and intensity of any serious adverse event at any time during the study. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ELISA specific seroconversion rates and geometric mean titres (at all blood sampling time points). |  |  | 
| Neutralisation assay specific seroconversion rates and geometric mean titres (at all blood sampling time points). |  |  |