A Phase II Trial to Compare a Liquid-frozen and a Freeze-dried Formulation of IMVAMUNE (MVA-BN®) Smallpox Vaccine in Vaccinia-naïve Healthy Subjects
Condition: Smallpox
MeSH terms: Vaccinia; Smallpox
Intervention: LF formulation of IMVAMUNE®; FD formulation of IMVAMUNE®
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: 651.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      A randomized, double-blind, multicenter Phase II trial to compare the immunogenicity and
      safety of a liquid-frozen and a freeze-dried formulation of IMVAMUNE (MVA-BN®) smallpox
      vaccine in vaccinia-naïve healthy subjects
    

Eligibility criteria:

        Inclusion criteria

          1. Male and female subjects, 18-55 years of age

          2. The subject has read, signed and dated 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 and has signed the Health Insurance
             Portability and Accountability Act (HIPAA) authorization form

          3. Body Mass Index (BMI) ≥ 18.5 and < 35

          4. 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)

          5. WOCBP must have a negative serum pregnancy test at screening (SCR) and a negative
             urine pregnancy test within 24 hours prior to each vaccination

          6. White blood cells ≥ 2500/mm3 and < ULN

          7. Absolute neutrophil count (ANC) within normal limits

          8. Hemoglobin within normal limits

          9. Platelets within normal limits

         10. 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)

         11. Adequate hepatic function defined as:

               -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN) in the absence of other
                  evidence of significant liver disease

               -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline
                  phosphatase < 1.5 x ULN

         12. Troponin I < 2 x ULN

         13. 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 (PVC) in a row, ST elevation consistent with
             ischemia

        Exclusion criteria

          1. Typical vaccinia scar

          2. Known or suspected history of smallpox vaccination

          3. History of vaccination with any poxvirus-based vaccine

          4. US Military service before 1991 or after January 2003

          5. Pregnant or breast-feeding women

          6. Uncontrolled serious infection, i.e. not responding to antimicrobial therapy

          7. 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 in the opinion of the investigator

          8. History of or active autoimmune disease, persons with vitiligo or thyroid disease
             taking thyroid hormone replacement are not excluded

          9. Known or suspected impairment of immunologic function including, but not limited to,
             clinically significant liver disease, diabetes mellitus, moderate to severe kidney
             impairment

         10. 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

         11. History or clinical manifestation of clinically significant and severe hematological,
             pulmonary, central nervous, cardiovascular or gastrointestinal disorders

         12. Clinically significant mental disorder not adequately controlled by medical treatment

         13. 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

         14. History of an immediate family member (father, mother, brother, or sister) who has had
             onset of ischemic heart disease before the age of 50 years

         15. 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 NOTE: This criterion
             applies only to subjects 20 years of age and older

         16. Active or history of chronic alcohol abuse and/or intravenous and/or nasal drug abuse
             (within the past 6 months)

         17. Known allergy to IMVAMUNE® vaccine and its constituents, e.g.
             tris(hydroxymethyl)-amino methane, including known allergy to egg or aminoglycoside
             (gentamycin)

         18. History of anaphylaxis or severe allergic reaction to any vaccine

         19. Acute disease (illness with or without a fever) at the time of enrollment

         20. Body Temperature ≥ 100.4°F (38.0°C) at the time of enrollment

         21. Having received any vaccinations or planned vaccinations with a live vaccine within 30
             days prior or after trial vaccination

         22. Having received any vaccinations or planned vaccinations with a killed vaccine within
             14 days prior or after trial vaccination

         23. 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 (Visit 5)

         24. Post organ transplant subjects whether or not receiving chronic immunosuppressive
             therapy

         25. 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 (Visit 5)

         26. 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 (with the day of the FU call
             being considered the last day of the trial period).

         27. Trial personnel