Smallpox
Conditions
Brief summary
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.
Interventions
BIOLOGICALIMVAMUNE (MVA-BN)
Two vaccinations of 0.5 ml MVA-BN vaccine, separated by a 4 week interval.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Bavarian Nordic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ELISA seroconversion rate | Day 42 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ELISA GMT | Days 28, 42, 84 | 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'. |
| PRNT seroconversion rate | Days 28, 42, 84 | 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. |
| PRNT GMT | Days 28, 42, 84 | 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'. |
| Cytotoxic T-Lymphocyte response | Days 28, 42, 84 | The Cytotoxic T-Lymphocyte (CTL) response was determined by measuring IFNγ producing cells by Intracellular cytokine staining (ICS) |
| ELISA seroconversion rate | Days 28, 84 | 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. |
| Solicited Local Adverse Events | within 8 days after any vaccination | Incidence and intensity of solicited local AEs. Percentages based on subjects with at least one completed diary card. |
| Solicited General Adverse Events | within 8 days after any vaccination | Incidence of solicited general AEs: Intensity and relationship to vaccination. Percentages based on subjects with at least one completed diary card. |
| Unsolicited Non-serious Adverse Events | within 31 days after any vaccination | Occurrence of unsolicited non-serious AEs: Intensity and relationship to vaccination |
| Serious Adverse Events | within 12 weeks | Incidence, relationship and intensity of any Serious Adverse Event (SAE) |
Countries
Switzerland
Outcome results
None listed