A Trial to Evaluate Immunogenicity and Safety of Three Consecutive Production Lots of IMVAMUNE® (MVA-BN®) Smallpox Vaccine in Healthy, Vaccinia-naïve Subjects
Condition: Smallpox
MeSH terms: Vaccinia; Smallpox
Intervention: IMVAMUNE®; Placebo
Intervention description: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose); 0.5 ml TBS
Intervention MeSH terms: Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 4005.0
Sex: All
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      A randomized, double-blind, placebo-controlled Phase III trial to evaluate immunogenicity and
      safety of three consecutive production lots of IMVAMUNE® (MVA-BN®) smallpox vaccine in
      healthy, vaccinia-naïve subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female subjects, 18 to 40 years of age

          -  The subject has read, signed and dated the informed consent form, having been advised
             of the risks and benefits of the trial in a language understood by the subject and
             prior to performance of any trial specific procedures

          -  BMI ≥ 18.5 and < 35

          -  Women of childbearing potential (WOCBP) 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 trial, and must avoid becoming pregnant
             for at least 28 days after the last vaccination. A woman is considered of childbearing
             potential unless post-menopausal or with a history of hysterectomy (Acceptable
             contraception methods are restricted to abstinence, barrier contraceptives,
             intrauterine contraceptive devices or licensed hormonal products)

          -  WOCBP must have a negative serum pregnancy test at screening and a negative urine
             pregnancy test within 24 hours prior to each vaccination

          -  White blood cells ≥ 2,500/mm3 < ULN

          -  Absolute neutrophil count (ANC) within normal limits

          -  Hemoglobin within normal limits

          -  Platelets within normal limits

          -  Adequate renal function defined as a calculated Creatinine Clearance (CrCl) > 60
             ml/min as estimated by the Cockcroft-Gault equation:

               -  For men: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dl
                  x 72) = CrCl (ml/min)

               -  For women: multiply the result by 0.85 = CrCl (ml/min).

          -  Adequate hepatic function defined as:

               -  a. Total bilirubin ≤ 1.5 x ULN in the absence of other evidence of significant
                  liver disease

               -  b. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline
                  phosphatase ≤ 1.5 x ULN

          -  Troponin I < 2 x ULN

          -  Electrocardiogram (ECG) without clinically significant 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 in a row, ST elevation consistent with ischemia)

        Exclusion criteria

          -  Typical vaccinia scar

          -  Known or suspected history of smallpox vaccination

          -  History of vaccination with any poxvirus-based vaccine

          -  US Military service prior to 1991 or after January 2003

          -  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 or would limit the subject's ability to
             complete the trial

          -  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,
             HIV Infection, clinically significant liver disease (including chronic active HBV or
             HCV), 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 tumor site

          -  History or clinical manifestation of clinically significant and severe hematological,
             pulmonary, central nervous, cardiovascular or gastrointestinal disorders

          -  Clinically significant mental disorder not adequately controlled by medical treatment

          -  History of coronary heart disease, myocardial infarction, angina pectoris, congestive
             heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high
             blood pressure, or any other heart condition under the care of a doctor

          -  Known history of an immediate family member (father, mother, brother, or sister) who
             has had onset of ischemic heart disease before age 50 years

          -  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 subjects 20 years of age and older

          -  Active or history of chronic alcohol abuse and/or intravenous and/or nasal drug abuse
             (within the past 6 months)

          -  Known allergy to IMVAMUNE® vaccine and its constituents, e.g. tris
             (hydroxymethyl)-amino methane, including know allergy to egg or aminoglycosides

          -  History of anaphylaxis or severe allergic reaction to any vaccine

          -  Acute disease (illness with or without a fever) at the time enrollment

          -  Body temperature ≥100.4°F (≥38.0°C) at the time of enrollment

          -  Having received any vaccinations or planned vaccinations with a live vaccine within 30
             days prior to or after trial vaccination

          -  Having received any vaccinations or planned vaccinations with a killed vaccine within
             14 days prior to or after trial vaccination

          -  Chronic systemic administration (defined as more than 14 days) of > 5 mg prednisone
             (or equivalent)/day or any other immune-modifying drugs during a period starting from
             three months prior to administration of the vaccine and ending at last physical trial
             visit (V5)

          -  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 three months prior to administration of the vaccine and
             ending at last physical trial visit (V5)

          -  Use of any investigational or non-registered drug or vaccine other than the trial
             vaccine within 30 days preceding the first dose of the trial vaccine, or planned
             administration of such a drug during the trial period

          -  Trial personnel