An Open-Label Phase II Study to Evaluate Immunogenicity and Safety of a Single IMVAMUNE Booster Vaccination Two Years After the Last IMVAMUNE Vaccination in Former POX-MVA-005 Vaccinees
Condition: Smallpox
MeSH terms: Smallpox
Intervention: IMVAMUNE; IMVAMUNE; Blood Draw Only
Intervention description: 1x 10E8_TCID50; 1x 10E8_TCID50
Intervention MeSH terms: Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 304.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The study was preformed to evaluate the persistence of antibodies following vaccination with
      MVA-BN and to assess the immunological memory response induced by a booster vaccination with
      MVA-BN in subjects two years after their participation in trial POX-MVA-005 (NCT00316524) in
      which they had received one or two doses of MVA-BN.
    

Eligibility criteria:

        Inclusion Criteria:

        Groups 1 and 2 (first consenting 75 subjects in each group to be vaccinated)

          -  Male and female subjects having participated in Group 1 or 2 of the study POX-MVA-005
             who completed the trial according to protocol.

          -  Women of childbearing potential 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 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 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.)

          -  Read, signed and dated informed consent document after being advised of the risks and
             benefits of the study in a language understood by the subject signed, and prior to
             performance of any study specific procedure.

          -  Troponin I within normal institutional limits.

          -  White blood cells ≥ 2,500/mm3 and <= 11,000/mm3.

          -  Absolute neutrophil count within normal limits.

          -  Negative urine glucose by dipstick or urinalysis.

          -  Hemoglobin within the laboratory reference ranges (unless the investigator considers
             the deviation to be not clinically significant).

          -  Platelets 100 - 440/nL.

          -  Adequate renal function defined as:

               1. Serum creatinine without clinically significant findings.

               2. Urine protein <= 30 mg/dL or none or trace proteinuria (by urinalysis or dip
                  stick).

          -  Adequate hepatic function defined as:

               1. Total bilirubin <= 1.5 x upper limit of normal (ULN) in the absence of other
                  evidence of significant liver disease (healthy subjects without clinical disease;
                  Morbus Meulengracht can be included).

               2. AST (SGOT), ALT (SGPT), alkaline phosphatase without clinically significant
                  findings.

          -  Electrocardiogram (ECG) without clinically relevant 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, two
             premature ventricular contractions (PVC) in a row, ST elevation consistent with
             ischemia).

        Group 4 (all subjects) and Groups 1 and 2 (subjects N > 75): blood draw only

          -  Male and female subjects having participated in the study POX-MVA-005 who completed
             the trial according to protocol.

          -  Read, signed and dated informed consent document after being advised of the risks and
             benefits of the blood draw in a language understood by the subject signed, and prior
             to performance of the blood draw.

        Exclusion Criteria:

        Groups 1 and 2 (first consenting 75 subjects in each group to be vaccinated)

          -  Participation in another study with a smallpox vaccine after the POX-MVA-005 study.

          -  Pregnant or breast-feeding women.

          -  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. 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 must not be vaccinated at the previous site of cancer.

          -  History or clinical manifestation of clinically significant and severe hematological,
             renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal
             disorders.

          -  Clinically significant mental disorder not adequately controlled by medical treatment.

          -  Any condition which might interfere with study objectives or would limit the subject's
             ability to complete the study or to be compliant in the opinion of the investigator.

          -  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.

          -  History of an immediate family member (father, mother, brother, or sister) who died
             due to ischemic heart disease before age 50 years.

          -  Twenty 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).

          -  History of intravenous drug abuse.

          -  History of allergic disease or reactions likely to be exacerbated by any component of
             the vaccine, e.g. tris (hydroxymethyl)-amino methane, chicken embryo fibroblast
             proteins, aminoglycosides (gentamycin).

          -  History of any anaphylactic shock or severe allergic reaction requiring immediate
             treatment.

          -  Having received any vaccinations or planned vaccinations with a live vaccine within 30
             days prior or after study vaccination.

          -  Having received any vaccinations or planned vaccinations with a killed vaccine within
             14 days prior or after study vaccination.

          -  Chronic administration (defined as more than 14 days) of > 5 mg prednisone (or
             equivalent) per day or any other immune-modifying drugs during a period starting from
             three months prior to administration of the vaccine and ending at study conclusion
             (Visit 4).

          -  Post organ transplant subjects whether or not receiving chronic immunosuppressive
             therapy.

          -  Administration or planned administration of immunoglobulins and/or any blood products
             during a period starting from 3 months prior to administration of the vaccine and
             ending at study conclusion.

          -  Use of any investigational or non-registered drug or vaccine other than the study
             vaccine within 30 days preceding administration of the study vaccine, or planned
             administration of such a drug during the study period.

        Group 4 (all subjects) and Groups 1 and 2 (subjects N > 75): blood draw only

          -  Participation in another study with a smallpox vaccine after the POX-MVA-005 study.

          -  Any condition which might interfere with a blood draw.