Lyophilized IMVAMUNE® (1x10^8 TCID50) Versus Liquid IMVAMUNE® (1x10^8 TCID50) Administered Subcutaneously and a Lower Dose Liquid IMVAMUNE® (2x10^7 TCID50) Administered Intradermally
Condition: Smallpox
MeSH terms: Smallpox
Intervention: MVA Smallpox Vaccine; MVA Smallpox Vaccine; MVA Smallpox Vaccine
Intervention description: Vaccinia vaccine liquid formulation delivered by subcutaneous (SC) route at 1x10^8 TCID50 per 0.5 mL dose on Days 0 and 28.; Vaccinia vaccine liquid formulation delivered at lower dose [2x10^7 tissue culture infectious dose 50 (TCID50) per 0.1 mL dose] by intradermal (ID) route on Days 0 and 28.; Vaccinia vaccine lyophilized formulation delivered by subcutaneous (SC) route at 1x10^8 TCID50 per 0.5 mL dose on Days 0 and 28.
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 523.0
Sex: All
Minimum age: 18 Years
Maximum age: 38 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: IMVAMUNE®, smallpox, vaccine

Summary:

      Due to recent concern of biowarfare and bioterrorism, the US government is making efforts to
      improve its ability to protect citizens against the smallpox virus. This study will evaluate
      safety of IMVAMUNE®, an investigational smallpox vaccine, and its ability to stimulate the
      immune system (the body's defense system). Two vaccine preparations have the same name but
      one is a liquid and one is a powder that has liquid added just before it is given. The
      vaccine that comes as a liquid will be injected (given as a shot) just under the skin
      (subcutaneously) or injected between the layers of the skin (intradermally). The powder
      formulation is only injected just under the skin. Approximately 495 adults, age 18 older born
      after 1971, which have not had smallpox vaccine before, may participate in the study for
      about 7 months.
    

Eligibility criteria:

        Inclusion Criteria:

        Inclusion criteria that must be met prior to the initial vaccination:

          -  At least 18 years of age and born after 1971.

          -  Read, signed, and dated informed consent document.

          -  Available for follow-up for the planned duration of the study (6 months after last
             immunization).

          -  Acceptable medical history by screening evaluation and limited physical assessment.

          -  If the subject is female and of childbearing potential, negative serum pregnancy test
             at screening and negative urine or serum pregnancy test within 24 hours prior to
             vaccination.

          -  If the subject is female and of childbearing potential, she agrees to use acceptable
             contraception, and not become pregnant for 28 days following the last vaccination:

               1. A woman is considered of childbearing potential unless post-menopausal (greater
                  than or equal to 1 year) or surgically sterilized (tubal ligation, bilateral
                  oophorectomy, or hysterectomy).

               2. Acceptable contraception methods are restricted to effective devices
                  [intrauterine devices (IUD)s, NuvaRing®] or licensed hormonal products with use
                  of method for a minimum of 30 days prior to vaccination, abstinence from sexual
                  intercourse with men (vaginal penetration by a penis, coitus), and monogamous
                  relationship with a vasectomized partner.

          -  Negative enzyme linked immunosorbent assay (ELISA) for human immunodeficiency virus
             (HIV).

          -  Alanine aminotransferase (ALT) <1.25 times institutional upper limit of normal.

          -  Negative hepatitis B surface antigen and negative antibody to hepatitis C virus.

          -  Negative urine glucose and urine protein <1 plus by dipstick or urinalysis.

          -  Adequate renal function is defined as a serum creatinine not exceeding the
             institution's upper limit of normal.

          -  Electrocardiogram (ECG) in absence of clinical significance (e.g., complete left or
             right bundle branch block, incomplete left bundle branch block or sustained
             ventricular arrhythmia, or 2 premature ventricular contraction's (PVC)'s in a row, or
             sympathetic tonus (ST) elevation consistent with ischemia).

          -  The following blood parameters:

               1. Hemoglobin equal or above the lower limit of institutional normal (sex-specific);

               2. White blood cells greater than 2,500 and less than 11,000/mm^3;

               3. Platelets greater than or equal to 140,000/mm^3.

          -  Weight: greater than or equal to 110 pounds.

        Inclusion Criteria that must be met prior to the second vaccination:

          -  Acceptable medical history.

          -  If the subject is female and of childbearing potential, negative urine or serum
             pregnancy test within 24 hours prior to vaccination.

          -  If the subject is female and of childbearing potential, she agrees to use acceptable
             contraception, and not become pregnant for 28 days following the last vaccination:

               1. A woman is considered of childbearing potential unless post-menopausal (greater
                  than or equal to 1 year) or surgically sterilized (tubal ligation, bilateral
                  oophorectomy, or hysterectomy).

               2. Acceptable contraception methods are restricted to effective devices (IUDs,
                  NuvaRing®) or licensed hormonal products with use of method for a minimum of 30
                  days prior to vaccination, abstinence from sexual intercourse with men (vaginal
                  penetration by a penis, coitus), and monogamous relationship with a vasectomized
                  partner.

        Exclusion Criteria:

        Exclusion criteria that apply prior to the initial vaccination:

          -  History of immunodeficiency

          -  Typical vaccinia scar

          -  Known or suspected history of smallpox vaccination including Modified Vaccinia Ankara
             (MVA) alone or as a vector as well as other investigational smallpox vaccine

          -  Military service prior to 1991 or after January 2003

          -  Known or suspected impairment of immunologic function including, but not limited to,
             clinically significant liver disease, diabetes mellitus, or moderate to severe kidney
             impairment

          -  Malignancy not including squamous cell skin cancer or basal cell skin cancer unless at
             the vaccination site or history of skin cancer at the vaccination site

          -  Active autoimmune disease

             a. Persons with vitiligo or thyroid disease (e.g., taking thyroid hormone replacement)
             are not excluded

          -  History of myocardial infarction, angina, congestive heart failure, cardiomyopathy,
             stroke or transient ischemic attack, or other heart condition under the care of a
             doctor

          -  Systolic blood pressure greater than or equal to 150 mmHg or diastolic blood pressure
             greater than or equal to 100 mmHg

          -  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://hp2010.nhlbihin.net/atpiii/calculator.asp)

        NOTE that this criterion applies only to subjects 20 years of age and older AND only if at
        least one of the following apply:

        a. have smoked a cigarette in the past month, and/or b. have hypertension (defined as
        systolic blood pressure >140 mm Hg) or are on antihypertensive medication, and/or c. have a
        family history of coronary heart disease in male first-degree relative (father or brother)
        <55 years of age or a female first-degree relative (mother or sister) <65 years of age

          -  High-dose steroid use for greater than 2 weeks duration within three months prior to
             vaccination and current use of immunosuppressive medication

               1. Corticosteroid nasal sprays are permissible

               2. Persons who are using a topical steroid can be enrolled after their therapy is
                  completed

               3. Inhaled steroids for asthma are not permissible

          -  Medical or psychiatric condition or occupational responsibilities that preclude
             subject compliance with the protocol

          -  Any history of illegal injection drug use

          -  Receipt or planned receipt of inactivated vaccine from 14 days prior to the first
             vaccination through 14 days post second vaccination

          -  Receipt or planned receipt of any other live attenuated vaccine within 30 days prior
             to the first vaccination through 30 days post second vaccination

          -  Use of any other experimental agent within 30 days prior to vaccination and for the
             duration of the study

          -  Receipt of blood products or immunoglobulin within six months prior to vaccination

          -  Donation of a unit of blood within 56 days prior to vaccination and prior to Visit 6

          -  Acute febrile illness (greater than or equal to 100.4 degrees Fahrenheit) on the day
             of vaccination

          -  Pregnant or lactating women

          -  Eczema of any degree or history of eczema

          -  Active atopic dermatitis, active exfoliative skin disorders/conditions, current
             Varicella zoster, or any acute skin disorders of large magnitude, e.g., laceration
             requiring sutures, burn greater than 2×2 cm

          -  Any condition that, in the opinion of the investigator, might interfere with study
             objectives

          -  Known allergy to IMVAMUNE® vaccine

          -  Known allergy to egg or aminoglycoside (including gentamicin)

          -  Study personnel

        Exclusion criteria that apply prior to the second vaccination:

          -  Continued inflammation (erythema and/or induration) graded as moderate or severe at
             the site of the initial vaccination

          -  History of immunodeficiency

          -  Known or suspected impairment of immunologic function including, but not limited to,
             clinically significant liver disease, diabetes mellitus, or moderate to severe kidney
             impairment

          -  Malignancy not including squamous cell skin cancer or basal cell skin cancer unless at
             the vaccination site or history of skin cancer at the vaccination site

          -  Active autoimmune disease

             a. Persons with vitiligo or thyroid disease (e.g., taking thyroid hormone replacement)
             are not excluded

          -  History of myocardial infarction, angina, congestive heart failure, cardiomyopathy,
             stroke or transient ischemic attack, or other heart condition under the care of a
             doctor

          -  Systolic blood pressure greater than or equal to 150 mmHg or diastolic blood pressure
             greater than or equal to 100 mmHg

          -  High-dose steroid use for greater than 2 weeks duration within three months prior to
             vaccination and current use of immunosuppressive medication.

               1. Corticosteroid nasal sprays are permissible

               2. Persons who are using a topical steroid can be enrolled after their therapy is
                  completed

               3. Inhaled steroids for asthma are not permissible

          -  Medical or psychiatric condition or occupational responsibilities that preclude
             subject compliance with the protocol

          -  Any history of illegal injection drug use

          -  Receipt of or planned receipt of inactivated vaccine from 14 days prior to vaccination
             through 14 days post second vaccination

          -  Receipt of or planned receipt of any other live attenuated vaccine from 30 days prior
             to vaccination through 30 days post second vaccination

          -  Use of any other experimental agent within 30 days prior to vaccination and for the
             duration of the study

          -  Receipt of blood products or immunoglobulin within six months prior to vaccination

          -  Donation of a unit of blood within 56 days prior to vaccination and prior to Visit 6

          -  Acute febrile illness (greater than or equal to 100.4 degrees Fahrenheit) on the day
             of vaccination

          -  Pregnant or lactating women

          -  Eczema of any degree or history of eczema

          -  Active atopic dermatitis, active exfoliative skin disorders/conditions, current
             Varicella zoster, or any acute skin disorders of large magnitude, e.g., laceration
             requiring sutures, burn greater than 2×2 cm

          -  Any condition that, in the opinion of the investigator, might interfere with study
             objectives

          -  Known allergy to IMVAMUNE® vaccine

          -  Known allergy to egg or aminoglycoside (including gentamicin)