Dose-finding Study to Evaluate Immunogenicity of Three Different Dose Levels of the IMVAMUNE (MVA-BN) Smallpox Vaccine.

Study Overview
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Brief Summary
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The objective of the study is to find the optimal dose for the smallpox candidate vaccine IMVAMUNE (MVA-BN). For this purpose the study compares IMVAMUNE (MVA-BN) administered at three different dose levels.

Official Title
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Phase II, Double-blind, Randomised, Dose-finding Study to Evaluate the Immunogenicity of Three Different Doses of MVA-BN Smallpox Vaccine in 18-30 Year Old Smallpox naïve Healthy Subjects

Conditions
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Smallpox

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects, aged 18 - 30 years Signed informed consent after being advised of the risks and benefits of the study in a language able to understand, and prior to performance of any study specific procedure. Free of obvious health problems with acceptable medical history by screening evaluation and physical examination. Subject of not of child-bearing potential or all of the following: A urine/serum ß-HCG pregnancy test gives a negative result, use of adequate contraceptive precautions for 30 days before first vaccination. Exclusion Criteria: Known or suspected history of smallpox vaccination or typical vaccinia scar. Positive test result in MVA specific ELISA or PRNT at screening. Positive result in HIV or HCV antibody test at screening. HbsAG positive at screening. Pregnancy or breast-feeding. 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 autoimmune disease History of malignancy. History of chronic alcohol abuse and/or intravenous drug abuse. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. History of anaphylaxis or severe allergic reaction. Acute disease (a moderate or severe illness with or without a fever) at the time of enrolment. Any vaccinations within a period starting 30 days prior to administration of the vaccine and ending at study conclusion. Chronic administration of immuno-suppressants or other immune-modifying drugs. Administration or planned administration of immunoglobulins and/or any blood products during the study period. Use of any investigational or non-registered drug or vaccine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>healthy, vaccinia naïve subjects 2 x 10E7 TCID50 IMVAMUNE (MVA-BN), subcutaneous | Biological: IMVAMUNE (MVA-BN)<br>* Two vaccinations of 0.5 ml MVA-BN vaccine, separated by a 4 week interval.<br>|
| Active Comparator: Group 2<br>healthy, vaccinia naïve subjects 5 x 10E7 TCID50 IMVAMUNE (MVA-BN), subcutaneous | Biological: IMVAMUNE (MVA-BN)<br>* Two vaccinations of 0.5 ml MVA-BN vaccine, separated by a 4 week interval.<br>|
| Active Comparator: Group 3<br>healthy, vaccinia naïve subjects 1 x 10E8 TCID50 IMVAMUNE (MVA-BN), subcutaneous | Biological: IMVAMUNE (MVA-BN)<br>* Two vaccinations of 0.5 ml MVA-BN vaccine, separated by a 4 week interval.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ELISA seroconversion rate | Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit 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. | Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ELISA seroconversion rate | Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit 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. | Days 28, 84 | 
| 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'. | Days 28, 42, 84 | 
| PRNT seroconversion rate | Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit 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. | Days 28, 42, 84 | 
| 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'. | Days 28, 42, 84 | 
| Cytotoxic T-Lymphocyte response | The Cytotoxic T-Lymphocyte (CTL) response was determined by measuring IFNγ producing cells by Intracellular cytokine staining (ICS) | Days 28, 42, 84 | 
| Serious Adverse Events | Incidence, relationship and intensity of any Serious Adverse Event (SAE) | within 12 weeks | 
| Solicited Local Adverse Events | Incidence and intensity of solicited local AEs. Percentages based on subjects with at least one completed diary card. | within 8 days after any vaccination | 
| Solicited General Adverse Events | Incidence of solicited general AEs: Intensity and relationship to vaccination. Percentages based on subjects with at least one completed diary card. | within 8 days after any vaccination | 
| Unsolicited Non-serious Adverse Events | Occurrence of unsolicited non-serious AEs: Intensity and relationship to vaccination | within 31 days after any vaccination |