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Randomized, Open-label Phase II Trial to Assess the Safety and Immunogenicity of MVA-BN Smallpox Vaccine in Immunocompromised Subjects With HIV Infection

Sponsor
Bavarian Nordic (Industry)
Overall Status
Completed
CT.gov ID
NCT02038881
Collaborator
(none)
87
Enrollment
12
Locations
3
Arms
36.4
Actual Duration (Months)
7.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this clinical trial is to generate additional safety data in a highly immunocompromised population. HIV-infected persons are considered excellent candidates to represent the highly immunocompromised population for enrolment in this trial. Additionally, the immune system's response (protection against smallpox as measured by the amount of antibodies produced) following injections of MVA-BN® smallpox vaccine will be evaluated. All participants in this trial will be randomly and evenly assigned to one of three groups to receive two, three or four injections. Group 1 will receive the standard regime consisting of one dose at each vaccination time point, Group 2 will receive two doses at each vaccination time point and Group 3 will receive a booster vaccination 12 weeks after the standard vaccination schedule with MVA-BN® smallpox vaccine. Participation in the trial is scheduled to last up to 75 weeks.

Condition or Disease Intervention/Treatment Phase
  • Biological: IMVAMUNE®
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
87 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Randomized, Open-label Phase II Trial to Assess the Safety and Immunogenicity of MVA-BN Smallpox Vaccine When Increasing the Number of Injections Compared to the Standard Regimen in Immunocompromised Subjects With HIV Infection
Actual Study Start Date :
Apr 28, 2014
Actual Primary Completion Date :
May 10, 2017
Actual Study Completion Date :
May 10, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group 1 (standard regimen)

One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®)

Biological: IMVAMUNE®
0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
Other Names:
  • IMVANEX®
  • MVA-BN® smallpox vaccine

    		•
    Experimental: Group 2 (double dose regimen)

    Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®)

    Biological: IMVAMUNE®
    0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Other Names:
  • IMVANEX®
  • MVA-BN® smallpox vaccine

    		•
    Experimental: Group 3 (booster regimen)

    One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®)

    Biological: IMVAMUNE®
    0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Other Names:
  • IMVANEX®
  • MVA-BN® smallpox vaccine

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With SAEs [within 75 weeks]

      Occurrence, relationship and intensity of any serious AE (SAE)

    Secondary Outcome Measures

    1. Number of Participants With AESIs [within 75 weeks]

      Occurrence, relationship to the trial vaccine, and intensity of any adverse event of special interest (AESI)

    2. Number of Participants With Related Grade >=3 Adverse Events [within 29 days after any vaccination]

      Number of Participants with any Grade >=3 Adverse Event probably, possibly, or definitely related to the study vaccine. Pooled solicited and unsolicited AEs.

    3. Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination [within 29 days after any vaccination]

      Occurrence of unsolicited non-serious AEs by relationship to study vaccine

    4. Number of Unsolicited Non-serious Adverse Events: Intensity [within 29 days after any vaccination]

      Occurrence of unsolicited non-serious AEs by Intensity

    5. Number of Participants With Solicited Local Adverse Events [within 8 days after any vaccination]

      Number of participants with solicited local AEs (redness, swelling, induration, pruritus, and pain) by intensity. Percentages based on subjects with at least one completed diary card. [Injection site erythema, injection site swelling and injection site induration--all sizes measured in diameter with max severity of: 0=0, 1 = <30 mm, 2 = ≥30 - <100 mm, 3 = ≥100 mm. Injection site pruritus: 0=absent, 1=mild, 2=moderate, 3=severe. Injection site pain: 0=absent, 1=painful to touch, 2=painful when limb is moved, 3=spontaneously painful/prevents normal activity.]

    6. Number of Participants With Solicited General AEs [within 8 days after any vaccination]

      Number of Participants with solicited systemic/general AEs (pyrexia, headache, myalgia, nausea, fatigue, and chills) by intensity. Percentages based on subjects with at least one completed diary card. [Body temperature: 0 = <99.5 F (<37.5 C), 1 = ≥99.5 - <100.4 F (≥37.5 - <38.0 C), 2= ≥100.4 - <102.2 F (≥38.0 - <39.0 C), 3= ≥102.2 - <104.0 F (≥39.0 - <40.0 C), 4= ≥ 104.0 F (≥40.0 C); pyrexia is defined as oral temperature ≥ 100.4 F (≥ 38.0 C).] [Headache, myalgia, nausea, chills and fatigue: 0 = none, 1 = mild: easily tolerated, minimal discomfort and no interference with daily activity, 2 = moderate: some interference with daily activity, 3 = severe: prevents daily activity.]

    7. CD4+ T Cell Counts [within 15 days after each vaccination]

      Mean CD4+ T-cell counts over time

    8. Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points [within 64 weeks]

      GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.

    9. ELISA GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) [Week 6]

      GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.

    10. ELISA GMT 2 Weeks Following the Last Vaccination [Week 6 (Groups 1 and 2), Week 14 (Group 3)]

      GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.

    11. ELISA GMT During Follow-up [Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)]

      GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'. Participants discontinued prior to the follow-up visits are excluded.

    12. GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points [within 64 weeks]

      GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.

    13. PRNT GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) [Week 6]

      GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.

    14. PRNT GMT 2 Weeks Following the Last Vaccination [Week 6 (Groups 1 and 2), Week 14 (Group 3)]

      GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.

    15. PRNT GMT During Follow-up [Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)]

      GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'. Participants discontinued prior to the follow-up visits are excluded.

    16. Percentage of Participants With Seroconversion by ELISA [within 64 weeks]

      SC rate based on ELISA. SC is defined as the appearance of antibody titers >= detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.

    17. Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) [Week 6]

      SC rate based on ELISA. SC is defined as the appearance of antibody titers >= detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.

    18. Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Last Vaccination [Week 6 (Groups 1 and 2), Week 14 (Group 3)]

      SC rate based on ELISA. SC is defined as the appearance of antibody titers >= detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.

    19. Percentage of Participants With Seroconversion by ELISA During Follow-up [Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)]

      SC rate based on ELISA. SC is defined as the appearance of antibody titers >= detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.

    20. Percentage of Participants With Seroconversion by PRNT [within 64 weeks]

      SC rate based on PRNT. SC is defined as the appearance of antibody titers >= detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.

    21. Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) [Week 6]

      SC rate based on PRNT. SC is defined as the appearance of antibody titers >= detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.

    22. Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Last Vaccination [Week 6 (Groups 1 and 2), Week 14 (Group 3)]

      SC rate based on PRNT. SC is defined as the appearance of antibody titers >= detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.

    23. Percentage of Participants With Seroconversion by PRNT During Follow-up [Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)]

      SC rate based on PRNT. SC is defined as the appearance of antibody titers >= detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Male and female subjects aged between 18-45 years, vaccinia-naïve.

    2. HIV-1 infection documented by ELISA and confirmed by Western blot at any time prior to study entry. HIV-1 deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), HIV-1 culture, HIV-1 antigen, plasma HIV-1 ribonucleic acid (RNA), or a second antibody test other than ELISA is acceptable as an alternative test at any time prior to study entry.

    3. On stable antiretroviral therapy (ART) i.e. Combination ART for at least 6 months. Subject must be on the same ART regimen for at least 12 weeks with no change prior to enrollment in this clinical trial.

    4. Screening HIV-1 RNA < 200 copies/ml by US Food and Drug Administration (FDA) approved PCR assay within 45 days prior to study entry.

    5. Current CD4 counts ≥ 100 cells/µl ≤ 500 cells/µl.

    6. Documented nadir CD4 count < 200 cells/µl at any time prior to enrollment.

    7. Hemoglobin ≥ 9.0 g/dl for female subjects, ≥ 10.0 g/dl or male subjects.

    8. Platelets ≥ 100,000/mm3.

    9. Ability and willingness of subject to provide written informed consent.

    10. Body Mass Index (BMI) ≥ 18.5 and < 35 kg/m2.

    11. 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 (defined as ≥ 12 months without a menstrual period) or surgically sterilized. Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products).

    12. WOCBP must have a negative serum pregnancy test at screening (SCR) and a negative urine pregnancy test within 24 hours prior to each vaccination.

    13. Absolute neutrophil count cells ≥ 750/mm3.

    14. Adequate renal function defined as a calculated Creatinine Clearance (CrCl) > 60 ml/min as estimated by the Cockcroft-Gault equation.

    15. For men: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dl x 72) = CrCl (ml/min)

    16. For women: multiply the result by 0.85 = CrCl (ml/min).Adequate hepatic function defined as: Total bilirubin ≤ 2 x upper limit normal (ULN) in the absence of other evidence of significant liver disease

    17. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 2.5 x ULN.

    18. Troponin I < 2 x ULN at entry in the clinical trial.

    19. 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. Pregnant or breast-feeding women.

    2. Typical vaccinia scar.

    3. Known or suspected history of smallpox vaccination.

    4. History of vaccination with any poxvirus-based vaccine.

    5. Uncontrolled serious infection, i.e. not responding to antimicrobial therapy.

    6. 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 including uncontrolled diabetes as according to the 'Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events' Version 1.0, December 2004, Clarification August 2009.

    7. History of or active autoimmune disease, persons with vitiligo or thyroid disease taking thyroid replacement are not excluded.

    8. Known or suspected impairment of immunologic function except those defined in the inclusion criteria, including, but not limited to clinically significant liver disease, diabetes mellitus type I and moderate to severe kidney impairment.

    9. 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.

    10. History or clinical manifestation of clinically significant and severe hematological, pulmonary, central nervous, cardiovascular or gastrointestinal disorders (except HIV infection, chronic or active Hepatitis-B-Virus or Hepatitis-C-Virus infection).

    11. Clinically significant psychiatric disorder not adequately controlled by medical treatment.

    12. 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.

    13. Known history of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before age 50 years.

    14. 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.

    15. Current alcohol abuse (40 g/day for at least 6 month) and/or intravenous and/or intranasal drug abuse (within the past 6 months).

    16. Known allergy to MVA-BN® vaccine or any of its constituents, e.g. tris (hydroxymethyl)-amino methane, including known allergy to egg or aminoglycosides.

    17. History of anaphylaxis or severe allergic reaction to any vaccine.

    18. Acute disease (illness with or without a fever) at the time of enrollment.

    19. Body temperature ≥ 100.4°F (≥ 38.0°C) at the time of enrollment.

    20. Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior to or after trial vaccination.

    21. Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior to or after trial vaccination.

    22. Use of immunosuppressant or immunomodulatory agents including systemic glucocorticoids (excluding nasal or inhaled steroids), tacrolimus, sirolimus, rapamycin, mycophenolate, cyclosporine, TNF-alpha blockers or antagonists, azathioprine, interferon, growth factors, or intravenous immunoglobulin in the 60 days prior to enrollment in this clinical trial.

    23. Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy.

    24. 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.

    25. 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.

    26. Trial personnel.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294
    2 Health for Life Clinic Little Rock Little Rock Arkansas United States 72207
    3 Quest Clinical Research San Francisco California United States 94115
    4 Dupont Circle Physicians Group Washington District of Columbia United States 20009
    5 Infectious Disease Associats of NW Florida Center for Prevention and Treatment of Infections Infectious Diseases Associates of NW FL Pensacola Florida United States 32504
    6 Rowan Tree Medical Wilton Manors Florida United States 33305
    7 University of Illinois - Chicago Chicago Illinois United States 60612
    8 University of Iowa Departments of Internal Medicine and Microbiology University of Iowa Iowa City Iowa United States 52242
    9 Washington University School of Medicine Saint Louis Missouri United States 63110
    10 University of Pennsylvania Clinical Trials Unit Philadelphia Pennsylvania United States 19104
    11 Clinical Research Puerto Rico, Inc. San Juan Puerto Rico 009091711
    12 Fundacion de Investigacion San Juan Puerto Rico 00927

    Sponsors and Collaborators

    • Bavarian Nordic

    Investigators

    • Principal Investigator: Edgar T Overton, MD, University of Alabama at Birmingham

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Bavarian Nordic
    ClinicalTrials.gov Identifier:
    NCT02038881
    Other Study ID Numbers:
    • POX-MVA-037
    First Posted:
    Jan 17, 2014
    Last Update Posted:
    Apr 2, 2020
    Last Verified:
    Mar 1, 2020
    Additional relevant MeSH terms:
    HIV Infections
    Smallpox
    Vaccines

    Study Results

    Participant Flow

    Recruitment Details Subjects were screened and enrolled at 12 sites in the US
    Pre-assignment Detail
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Period Title: Overall Study
    STARTED 27 29 31
    COMPLETED 24 29 30
    NOT COMPLETED 3 0 1

    Baseline Characteristics

    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen) Total
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Total of all reporting groups
    Overall Participants 27 29 31 87
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    35.1
    (7.66)
    33.1
    (6.67)
    36.6
    (5.43)
    35
    (6.68)
    Sex: Female, Male (Count of Participants)
    Female
    4
    14.8%
    5
    17.2%
    3
    9.7%
    12
    13.8%
    Male
    23
    85.2%
    24
    82.8%
    28
    90.3%
    75
    86.2%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaskan Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Oriental/Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black/African American
    16
    59.3%
    18
    62.1%
    16
    51.6%
    50
    57.5%
    Native Hawaiian/Other Pacific Islander
    0
    0%
    0
    0%
    1
    3.2%
    1
    1.1%
    White/Caucasian
    10
    37%
    10
    34.5%
    14
    45.2%
    34
    39.1%
    Other
    1
    3.7%
    1
    3.4%
    0
    0%
    2
    2.3%
    Hispanic or Latino
    5
    18.5%
    4
    13.8%
    3
    9.7%
    12
    13.8%
    Not Hispanic or Latino
    22
    81.5%
    25
    86.2%
    28
    90.3%
    75
    86.2%
    Region of Enrollment (participants) [Number]
    United States
    27
    100%
    29
    100%
    31
    100%
    87
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With SAEs
    Description Occurrence, relationship and intensity of any serious AE (SAE)
    Time Frame within 75 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 27 29 31
    Any SAE
    0
    0%
    0
    0%
    2
    6.5%
    Any SAE with intensity >= Grade 3
    0
    0%
    0
    0%
    2
    6.5%
    Any SAE assessed as related to vaccine
    0
    0%
    0
    0%
    0
    0%
    2. Secondary Outcome
    Title Number of Participants With AESIs
    Description Occurrence, relationship to the trial vaccine, and intensity of any adverse event of special interest (AESI)
    Time Frame within 75 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 27 29 31
    Any AESI
    0
    0%
    0
    0%
    1
    3.2%
    Any AESI with intensity >= Grade 3
    0
    0%
    0
    0%
    0
    0%
    Any AESI assessed as related to vaccine
    0
    0%
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Number of Participants With Related Grade >=3 Adverse Events
    Description Number of Participants with any Grade >=3 Adverse Event probably, possibly, or definitely related to the study vaccine. Pooled solicited and unsolicited AEs.
    Time Frame within 29 days after any vaccination

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 27 29 31
    Count of Participants [Participants]
    4
    14.8%
    5
    17.2%
    3
    9.7%
    4. Secondary Outcome
    Title Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination
    Description Occurrence of unsolicited non-serious AEs by relationship to study vaccine
    Time Frame within 29 days after any vaccination

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 27 29 31
    Unrelated/None
    4
    4
    13
    Unlikely
    1
    2
    1
    Possible
    1
    1
    0
    Probable
    0
    0
    1
    Definite
    0
    0
    0
    5. Secondary Outcome
    Title Number of Unsolicited Non-serious Adverse Events: Intensity
    Description Occurrence of unsolicited non-serious AEs by Intensity
    Time Frame within 29 days after any vaccination

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 27 29 31
    Mild
    4
    7
    9
    Moderate
    1
    0
    6
    Severe
    1
    0
    0
    6. Secondary Outcome
    Title Number of Participants With Solicited Local Adverse Events
    Description Number of participants with solicited local AEs (redness, swelling, induration, pruritus, and pain) by intensity. Percentages based on subjects with at least one completed diary card. [Injection site erythema, injection site swelling and injection site induration--all sizes measured in diameter with max severity of: 0=0, 1 = <30 mm, 2 = ≥30 - <100 mm, 3 = ≥100 mm. Injection site pruritus: 0=absent, 1=mild, 2=moderate, 3=severe. Injection site pain: 0=absent, 1=painful to touch, 2=painful when limb is moved, 3=spontaneously painful/prevents normal activity.]
    Time Frame within 8 days after any vaccination

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 27 29 31
    Injection Site Pain, Grade 1
    5
    18.5%
    4
    13.8%
    11
    35.5%
    Injection Site Pain, Grade 2
    10
    37%
    11
    37.9%
    10
    32.3%
    Injection Site Pain, Grade 3
    2
    7.4%
    4
    13.8%
    1
    3.2%
    Injection Site Erythema, Grade 1
    7
    25.9%
    11
    37.9%
    15
    48.4%
    Injection Site Erythema, Grade 2
    1
    3.7%
    0
    0%
    3
    9.7%
    Injection Site Erythema, Grade 3
    0
    0%
    0
    0%
    0
    0%
    Injection Site Swelling, Grade 1
    9
    33.3%
    9
    31%
    9
    29%
    Injection Site Swelling, Grade 2
    1
    3.7%
    1
    3.4%
    4
    12.9%
    Injection Site Swelling, Grade 3
    0
    0%
    0
    0%
    0
    0%
    Injection Site Induration, Grade 1
    7
    25.9%
    5
    17.2%
    9
    29%
    Injection Site Induration, Grade 2
    1
    3.7%
    1
    3.4%
    1
    3.2%
    Injection Site Induration, Grade 3
    0
    0%
    0
    0%
    0
    0%
    Injection Site Pruritus, Grade 1
    7
    25.9%
    6
    20.7%
    15
    48.4%
    Injection Site Pruritus, Grade 2
    4
    14.8%
    2
    6.9%
    3
    9.7%
    Injection Site Pruritus, Grade 3
    1
    3.7%
    0
    0%
    0
    0%
    7. Secondary Outcome
    Title Number of Participants With Solicited General AEs
    Description Number of Participants with solicited systemic/general AEs (pyrexia, headache, myalgia, nausea, fatigue, and chills) by intensity. Percentages based on subjects with at least one completed diary card. [Body temperature: 0 = <99.5 F (<37.5 C), 1 = ≥99.5 - <100.4 F (≥37.5 - <38.0 C), 2= ≥100.4 - <102.2 F (≥38.0 - <39.0 C), 3= ≥102.2 - <104.0 F (≥39.0 - <40.0 C), 4= ≥ 104.0 F (≥40.0 C); pyrexia is defined as oral temperature ≥ 100.4 F (≥ 38.0 C).] [Headache, myalgia, nausea, chills and fatigue: 0 = none, 1 = mild: easily tolerated, minimal discomfort and no interference with daily activity, 2 = moderate: some interference with daily activity, 3 = severe: prevents daily activity.]
    Time Frame within 8 days after any vaccination

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 27 29 31
    Pyrexia, Grade 1
    0
    0%
    0
    0%
    0
    0%
    Pyrexia, Grade 2
    1
    3.7%
    0
    0%
    0
    0%
    Pyrexia, Grade 3
    0
    0%
    0
    0%
    0
    0%
    Headache, Grade 1
    8
    29.6%
    5
    17.2%
    6
    19.4%
    Headache, Grade 2
    1
    3.7%
    3
    10.3%
    3
    9.7%
    Headache, Grade 3
    0
    0%
    2
    6.9%
    1
    3.2%
    Myalgia, Grade 1
    6
    22.2%
    6
    20.7%
    8
    25.8%
    Myalgia, Grade 2
    2
    7.4%
    6
    20.7%
    4
    12.9%
    Myalgia, Grade 3
    1
    3.7%
    0
    0%
    1
    3.2%
    Chills, Grade 1
    4
    14.8%
    4
    13.8%
    5
    16.1%
    Chills, Grade 2
    2
    7.4%
    2
    6.9%
    1
    3.2%
    Chills, Grade 3
    1
    3.7%
    0
    0%
    0
    0%
    Nausea, Grade 1
    3
    11.1%
    4
    13.8%
    4
    12.9%
    Nausea, Grade 2
    3
    11.1%
    0
    0%
    2
    6.5%
    Nausea, Grade 3
    0
    0%
    2
    6.9%
    0
    0%
    Fatigue, Grade 1
    5
    18.5%
    4
    13.8%
    5
    16.1%
    Fatigue, Grade 2
    2
    7.4%
    5
    17.2%
    5
    16.1%
    Fatigue, Grade 3
    2
    7.4%
    2
    6.9%
    1
    3.2%
    8. Secondary Outcome
    Title CD4+ T Cell Counts
    Description Mean CD4+ T-cell counts over time
    Time Frame within 15 days after each vaccination

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 27 29 31
    Screening
    304.9
    (104.77)
    295.3
    (111.10)
    349.6
    (133.71)
    Week 2
    337.4
    (118.18)
    357.0
    (157.87)
    335.7
    (111.11)
    Week 6
    319.1
    (117.91)
    365.4
    (197.04)
    345.0
    (96.22)
    Week 14
    NA
    (NA)
    NA
    (NA)
    351.9
    (114.53)
    9. Secondary Outcome
    Title Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points
    Description GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.
    Time Frame within 64 weeks

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 20 23 26
    Week 0
    1.5
    1.2
    1.8
    Week 4
    40.0
    47.1
    41.8
    Week 6
    552.2
    846.1
    726.1
    Week 12
    NA
    NA
    193.1
    Week 14
    NA
    NA
    1591.2
    Week 30/38
    34.6
    30.8
    143.3
    Week 56/64
    25.2
    27.5
    116.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 1 / Group 2) at Week 4
    Estimated Value 0.851
    Confidence Interval (2-Sided) 95%
    0.258 to 2.800
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 1 / Group 2) at Week 6
    Estimated Value 0.653
    Confidence Interval (2-Sided) 95%
    0.319 to 1.333
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 1 / Group 2) at Week 30
    Estimated Value 1.126
    Confidence Interval (2-Sided) 95%
    0.291 to 4.352
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 1 / Group 2) at Week 56
    Estimated Value 0.916
    Confidence Interval (2-Sided) 95%
    0.220 to 3.819
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 3 / Group 1) at Week 4
    Estimated Value 1.045
    Confidence Interval (2-Sided) 95%
    0.292 to 3.741
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 3 / Group 1) at Week 6
    Estimated Value 1.315
    Confidence Interval (2-Sided) 95%
    0.598 to 2.892
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title ELISA GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))
    Description GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.
    Time Frame Week 6

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 and 3 Combined Group 2
    Arm/Group Description Pooling of Groups 1 and 3 (same dose/regimen before booster vaccination in Group 3) Double dose regimen
    Measure Participants 46 23
    Geometric Mean (95% Confidence Interval) [Titer]
    644.6
    846.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 1+3 [pooled] / Group 2)
    Estimated Value 0.762
    Confidence Interval (2-Sided) 95%
    0.385 to 1.507
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title ELISA GMT 2 Weeks Following the Last Vaccination
    Description GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.
    Time Frame Week 6 (Groups 1 and 2), Week 14 (Group 3)

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 20 23 26
    Geometric Mean (95% Confidence Interval) [Titer]
    552.2
    846.1
    1591.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 1 [W6]/ Group 3 [W14)
    Estimated Value 0.347
    Confidence Interval (2-Sided) 95%
    0.200 to 0.603
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT ratio (Group 2 [W6]/ Group 3 [W14])
    Estimated Value 0.532
    Confidence Interval (2-Sided) 95%
    0.285 to 0.992
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title ELISA GMT During Follow-up
    Description GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'. Participants discontinued prior to the follow-up visits are excluded.
    Time Frame Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 18 22 24
    Week 30/38
    34.6
    30.8
    143.3
    Week 56/64
    25.2
    27.5
    116.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 3 [W38]/ Group 1 [W30])
    Estimated Value 4.138
    Confidence Interval (2-Sided) 95%
    1.241 to 13.793
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 3 [W64]/ Group 1 [W56])
    Estimated Value 4.608
    Confidence Interval (2-Sided) 95%
    1.365 to 15.558
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 2 [W30]/ Group 3 [W38])
    Estimated Value 0.215
    Confidence Interval (2-Sided) 95%
    0.066 to 0.699
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 2 [W56]/ Group 3 [W64])
    Estimated Value 0.237
    Confidence Interval (2-Sided) 95%
    0.072 to 0.782
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Secondary Outcome
    Title GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points
    Description GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.
    Time Frame within 64 weeks

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 20 23 26
    Week 0
    NA
    NA
    1.2
    Week 4
    3.9
    4.8
    10.1
    Week 6
    78.9
    100.3
    95.9
    Week 12
    NA
    NA
    35.5
    Week 14
    NA
    NA
    281.1
    Week 30/38
    6.2
    11.5
    41.5
    Week 56/64
    6.2
    10.6
    45.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 1 / Group 2) at Week 4
    Estimated Value 0.823
    Confidence Interval (2-Sided) 95%
    0.333 to 2.038
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 1 / Group 2) at Week 6
    Estimated Value 0.787
    Confidence Interval (2-Sided) 95%
    0.410 to 1.508
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 1 / Group 2) at Week 30
    Estimated Value 0.535
    Confidence Interval (2-Sided) 95%
    0.187 to 1.536
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 1 / Group 2) at Week 56
    Estimated Value 0.590
    Confidence Interval (2-Sided) 95%
    0.203 to 1.716
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 3 / Group 1) at Week 4
    Estimated Value 2.557
    Confidence Interval (2-Sided) 95%
    0.972 to 6.731
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 3 / Group 1) at Week 6
    Estimated Value 1.215
    Confidence Interval (2-Sided) 95%
    0.612 to 2.412
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title PRNT GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))
    Description GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.
    Time Frame Week 6

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 and 3 Combined Group 2
    Arm/Group Description Pooling of Groups 1 and 3 (same dose/regimen before booster vaccination in Group 3) Double dose regimen
    Measure Participants 46 23
    Geometric Mean (95% Confidence Interval) [Titer]
    88.1
    100.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 1+3 [pooled] / Group 2)
    Estimated Value 0.878
    Confidence Interval (2-Sided) 95%
    0.480 to 1.606
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Secondary Outcome
    Title PRNT GMT 2 Weeks Following the Last Vaccination
    Description GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.
    Time Frame Week 6 (Groups 1 and 2), Week 14 (Group 3)

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 20 23 26
    Geometric Mean (95% Confidence Interval) [Titer]
    78.9
    100.3
    281.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT ratio (Group 1 [W6]/ Group 3 [W14)
    Estimated Value 0.281
    Confidence Interval (2-Sided) 95%
    0.146 to 0.542
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT ratio (Group 2 [W6]/ Group 3 [W14])
    Estimated Value 0.357
    Confidence Interval (2-Sided) 95%
    0.178 to 0.718
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    16. Secondary Outcome
    Title PRNT GMT During Follow-up
    Description GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'. Participants discontinued prior to the follow-up visits are excluded.
    Time Frame Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 18 22 24
    Week 30/38
    6.2
    11.5
    41.5
    Week 56/64
    6.2
    10.6
    45.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 3 [W38]/ Group 1 [W30])
    Estimated Value 6.727
    Confidence Interval (2-Sided) 95%
    2.493 to 18.150
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 3 [W64]/ Group 1 [W56])
    Estimated Value 7.275
    Confidence Interval (2-Sided) 95%
    2.693 to 19.649
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 2 [W30]/ Group 3 [W38])
    Estimated Value 0.278
    Confidence Interval (2-Sided) 95%
    0.115 to 0.672
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter GMT Ratio (Group 2 [W56]/ Group 3 [W64])
    Estimated Value 0.233
    Confidence Interval (2-Sided) 95%
    0.100 to 0.541
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    17. Secondary Outcome
    Title Percentage of Participants With Seroconversion by ELISA
    Description SC rate based on ELISA. SC is defined as the appearance of antibody titers >= detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
    Time Frame within 64 weeks

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 20 23 26
    Week 4
    75.0
    82.6
    69.2
    Week 6
    100.0
    100.0
    92.3
    Week 12
    NA
    NA
    84.6
    Week 14
    NA
    NA
    100.0
    Week 30/38
    77.8
    72.7
    83.3
    Week 56/64
    66.7
    68.2
    83.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 1 - Gr 2) at Week 4
    Estimated Value -7.6
    Confidence Interval (2-Sided) 95%
    -34.1 to 17.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 1 - Gr 2) at Week 6
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -16.8 to 16.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 1 - Gr 2) at Week 30
    Estimated Value 5.1
    Confidence Interval (2-Sided) 95%
    -24.5 to 32.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 1 - Gr 2) at Week 56
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -31.5 to 29.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 3 - Gr 1) at Week 4
    Estimated Value -5.8
    Confidence Interval (2-Sided) 95%
    -32.8 to 22.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 3 - Gr 1) at Week 6
    Estimated Value -7.7
    Confidence Interval (2-Sided) 95%
    -25.1 to 10.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    18. Secondary Outcome
    Title Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))
    Description SC rate based on ELISA. SC is defined as the appearance of antibody titers >= detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
    Time Frame Week 6

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 and 3 Combined Group 2
    Arm/Group Description Pooling of Groups 1 and 3 (same dose/regimen before booster vaccination in Group 3) Double dose regimen
    Measure Participants 46 23
    Number (95% Confidence Interval) [percentage of subjects]
    95.7
    100.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in seroconversion rates (%)
    Estimated Value -4.3
    Confidence Interval (2-Sided) 95%
    -15.2 to 11.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    19. Secondary Outcome
    Title Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Last Vaccination
    Description SC rate based on ELISA. SC is defined as the appearance of antibody titers >= detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
    Time Frame Week 6 (Groups 1 and 2), Week 14 (Group 3)

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 20 23 26
    Number (95% Confidence Interval) [percentage of subjects]
    100.0
    100.0
    100.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 1 [W6] - Gr 3 [W14])
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -17.1 to 13.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 2 [W6] - Gr 3 [W14])
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -16.2 to 13.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    20. Secondary Outcome
    Title Percentage of Participants With Seroconversion by ELISA During Follow-up
    Description SC rate based on ELISA. SC is defined as the appearance of antibody titers >= detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
    Time Frame Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 18 22 24
    Week 30/38
    77.8
    72.7
    83.3
    Week 56/64
    66.7
    68.2
    83.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr3 [W38] - Gr1 [W30])
    Estimated Value 5.6
    Confidence Interval (2-Sided) 95%
    -19.6 to 33.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr3 [W64] - Gr1 [W56])
    Estimated Value 16.7
    Confidence Interval (2-Sided) 95%
    -11.0 to 44.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr2 [W30] - Gr3 [W38])
    Estimated Value -10.6
    Confidence Interval (2-Sided) 95%
    -35.6 to 14.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr2 [W56] - Gr3 [W64])
    Estimated Value -15.2
    Confidence Interval (2-Sided) 95%
    -40.5 to 10.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    21. Secondary Outcome
    Title Percentage of Participants With Seroconversion by PRNT
    Description SC rate based on PRNT. SC is defined as the appearance of antibody titers >= detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
    Time Frame within 64 weeks

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 20 23 26
    Week 4
    60.0
    69.6
    80.8
    Week 6
    100.0
    100.0
    96.2
    Week 12
    NA
    NA
    96.2
    Week 14
    NA
    NA
    100.0
    Week 30/38
    72.2
    81.8
    91.7
    Week 56/64
    66.7
    72.7
    95.8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 1 - Gr 2) at Week 4
    Estimated Value -9.6
    Confidence Interval (2-Sided) 95%
    -38.4 to 20.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 1 - Gr 2) at Week 6
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -16.8 to 16.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 1 - Gr 2) at Week 30
    Estimated Value -9.6
    Confidence Interval (2-Sided) 95%
    -38.4 to 17.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 1 - Gr 2) at Week 56
    Estimated Value -6.1
    Confidence Interval (2-Sided) 95%
    -35.6 to 23.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 3 - Gr 1) at Week 4
    Estimated Value 20.8
    Confidence Interval (2-Sided) 95%
    -7.7 to 47.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 3 - Gr 1) at Week 6
    Estimated Value -3.8
    Confidence Interval (2-Sided) 95%
    -20.5 to 13.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    22. Secondary Outcome
    Title Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))
    Description SC rate based on PRNT. SC is defined as the appearance of antibody titers >= detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
    Time Frame Week 6

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 and 3 Combined Group 2
    Arm/Group Description Pooling of Groups 1 and 3 (same dose/regimen before booster vaccination in Group 3) Double dose regimen
    Measure Participants 46 23
    Number (95% Confidence Interval) [percentage of subjects]
    97.8
    100.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 2 (Double Dose Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in seroconversion rates (%)
    Estimated Value -2.2
    Confidence Interval (2-Sided) 95%
    -12.0 to 13.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    23. Secondary Outcome
    Title Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Last Vaccination
    Description SC rate based on PRNT. SC is defined as the appearance of antibody titers >= detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
    Time Frame Week 6 (Groups 1 and 2), Week 14 (Group 3)

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 20 23 26
    Number (95% Confidence Interval) [percentage of subjects]
    100.0
    100.0
    100.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 1 [W6] - Gr 3 [W14])
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -17.1 to 13.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr 2 [W6] - Gr 3 [W14])
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -16.2 to 13.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    24. Secondary Outcome
    Title Percentage of Participants With Seroconversion by PRNT During Follow-up
    Description SC rate based on PRNT. SC is defined as the appearance of antibody titers >= detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
    Time Frame Weeks 30 and 56 (Groups 1 and 2), Weeks 38 and 64 (Group 3)

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Set
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    Measure Participants 18 22 24
    Week 30/38
    72.2
    81.8
    91.7
    Week 56/64
    66.7
    72.7
    95.8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr3 [W38] - Gr1 [W30])
    Estimated Value 19.4
    Confidence Interval (2-Sided) 95%
    -4.5 to 45.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Group 1 (Standard Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr3 [W64] - Gr1 [W56])
    Estimated Value 29.2
    Confidence Interval (2-Sided) 95%
    5.8 to 55.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr2 [W30] - Gr3 [W38])
    Estimated Value -9.8
    Confidence Interval (2-Sided) 95%
    -33.0 to 11.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Group 2 (Double Dose Regimen), Group 3 (Booster Regimen)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Diff in SC rate (Gr2 [W56] - Gr3 [W64])
    Estimated Value -23.1
    Confidence Interval (2-Sided) 95%
    -46.7 to -1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame within 75 weeks
    Adverse Event Reporting Description
    Arm/Group Title Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Arm/Group Description One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®) IMVAMUNE®: 0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
    All Cause Mortality
    Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/27 (0%) 0/29 (0%) 0/31 (0%)
    Serious Adverse Events
    Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/27 (0%) 0/29 (0%) 2/31 (6.5%)
    Gastrointestinal disorders
    Pancreatitis 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Psychiatric disorders
    Depression 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Other (Not Including Serious) Adverse Events
    Group 1 (Standard Regimen) Group 2 (Double Dose Regimen) Group 3 (Booster Regimen)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/27 (18.5%) 6/29 (20.7%) 10/31 (32.3%)
    Gastrointestinal disorders
    Inguinal hernia 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Vomiting 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    General disorders
    Influenza like illness 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Non-cardiac chest pain 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Hepatobiliary disorders
    Hyperbilirubinaemia 1/27 (3.7%) 1 0/29 (0%) 0 0/31 (0%) 0
    Infections and infestations
    Furuncle 1/27 (3.7%) 1 0/29 (0%) 0 0/31 (0%) 0
    Herpes zoster 1/27 (3.7%) 1 0/29 (0%) 0 0/31 (0%) 0
    Influenza 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Rhinitis 0/27 (0%) 0 1/29 (3.4%) 1 0/31 (0%) 0
    Skin bacterial infection 0/27 (0%) 0 1/29 (3.4%) 1 0/31 (0%) 0
    Upper respiratory tract infection 1/27 (3.7%) 1 0/29 (0%) 0 0/31 (0%) 0
    Injury, poisoning and procedural complications
    Human bite 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Laceration 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Ulna fracture 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Investigations
    Blood creatinine increased 0/27 (0%) 0 1/29 (3.4%) 1 1/31 (3.2%) 1
    Troponin I increased 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Myalgia 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Neck pain 0/27 (0%) 0 1/29 (3.4%) 1 0/31 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 0/27 (0%) 0 1/29 (3.4%) 1 1/31 (3.2%) 1
    Nasal congestion 0/27 (0%) 0 0/29 (0%) 0 1/31 (3.2%) 1
    Oropharyngeal pain 1/27 (3.7%) 1 0/29 (0%) 0 0/31 (0%) 0
    Productive cough 0/27 (0%) 0 1/29 (3.4%) 1 1/31 (3.2%) 1
    Sinus congestion 1/27 (3.7%) 1 0/29 (0%) 0 0/31 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash 0/27 (0%) 0 1/29 (3.4%) 1 0/31 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Program Lead, Clinical Operations
    Organization Bavarian Nordic A/S
    Phone +45 3326 ext 8383
    Email info@bavarian-nordic.com
    Responsible Party:
    Bavarian Nordic
    ClinicalTrials.gov Identifier:
    NCT02038881
    Other Study ID Numbers:
    • POX-MVA-037
    First Posted:
    Jan 17, 2014
    Last Update Posted:
    Apr 2, 2020
    Last Verified:
    Mar 1, 2020