A Randomized, Double-blind, Placebo-controlled Study on Immunogenicity and Safety of MVA-BN (IMVAMUNE™) Smallpox Vaccine in Healthy Subjects
Condition: Smallpox
MeSH terms: Smallpox
Intervention: MVA-BN® (IMVAMUNE); Placebo
Intervention description: 1x 10E8_TCID50; Tris-Buffer
Intervention MeSH terms: Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 745.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Smallpox; Vaccination; Prevention

Summary:

      The primary objective of this study is to evaluate the immune response after a single
      vaccination of pre-immune subjects compared to two vaccinations in naive subjects.

      In addition the study further investigates the cardiac safety profile of MVA-BN® in a healthy
      population compared to placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female subjects between 18 and 55 years of age.

          2. Women must have a negative serum pregnancy test at screening and a negative urine or
             serum pregnancy test within 24 hours prior to vaccination.

          3. 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. A woman is considered of childbearing potential unless
             post-menopausal or surgically sterilized. (Acceptable contraception methods are
             restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices
             or licensed hormonal products.)

          4. Lab values without clinically significant findings

          5. Electrocardiogram (ECG) without abnormal findings (e.g. any kind of atrioventricular
             or intraventricular conditions or blocks such as complete left or right bundle branch
             block, AV-node block, QTc or PR prolongation, premature atrial contractions or other
             atrial arrhythmia, sustained ventricular arrhythmia, 2 premature ventricular
             contractions (PVC) in a row, ST elevation consistent with ischemia).

        Groups 1, 2 and 3 (All vaccinia-naïve subjects) additionally:

          1. No history of known or suspected previous smallpox vaccination.

          2. No detectable vaccinia scar.

        Group 4 (All previously vaccinated subjects) additionally:

          1. History of previous smallpox vaccination (documented and/or typical vaccinia scar).

          2. Most recent smallpox vaccination ≥ 5 years.

        Exclusion Criteria:

          1. Uncontrolled serious infection i.e. not responding to antimicrobial therapy.

          2. History of or active autoimmune disease. Persons with vitiligo or thyroid disease
             taking thyroid replacement are not excluded.

          3. Known or suspected impairment of immunologic function including, but not limited to,
             clinically significant liver disease; diabetes mellitus; moderate to severe kidney
             impairment.

          4. 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.

          5. History of coronary heart disease, myocardial infarction, angina, congestive heart
             failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood
             pressure, or any other heart condition under the care of a doctor.

          6. History of an immediate family member (father, mother, brother, or sister) who died
             due to ischemic heart disease before age 50 years.

          7. 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.

          8. History of anaphylaxis or severe allergic reaction.

          9. Immune modulatory therapy.

         10. History of any serious medical condition, which in the opinion of the investigator
             would compromise the safety of the subject.

         11. History or clinical manifestation of clinically significant and severe hematological,
             renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal
             disorders.