Smallpox
Conditions
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.
Interventions
BIOLOGICALIMVAMUNE®
0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml
Sponsors
Bavarian Nordic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
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. 1. For men: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dl x 72) = CrCl (ml/min) 2. 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 15. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 2.5 x ULN. 16. Troponin I \< 2 x ULN at entry in the clinical trial. 17. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With SAEs | within 75 weeks | Occurrence, relationship and intensity of any serious AE (SAE) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| Number of Unsolicited Non-serious Adverse Events: Intensity | within 29 days after any vaccination | Occurrence of unsolicited non-serious AEs by Intensity |
| 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. \[Injection site erythema, injection site swelling and injection site induration--all sizes measured in diameter with max severity of: 0=0, 1 = \<30 mm, 2 = ≥30 - \<100 mm, 3 = ≥100 mm. Injection site pruritus: 0=absent, 1=mild, 2=moderate, 3=severe. Injection site pain: 0=absent, 1=painful to touch, 2=painful when limb is moved, 3=spontaneously painful/prevents normal activity.\] |
| 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. \[Body temperature: 0 = \<99.5 F (\<37.5 C), 1 = ≥99.5 - \<100.4 F (≥37.5 - \<38.0 C), 2= ≥100.4 - \<102.2 F (≥38.0 - \<39.0 C), 3= ≥102.2 - \<104.0 F (≥39.0 - \<40.0 C), 4= ≥ 104.0 F (≥40.0 C); pyrexia is defined as oral temperature ≥ 100.4 F (≥ 38.0 C).\] \[Headache, myalgia, nausea, chills and fatigue: 0 = none, 1 = mild: easily tolerated, minimal discomfort and no interference with daily activity, 2 = moderate: some interference with daily activity, 3 = severe: prevents daily activity.\] |
| CD4+ T Cell Counts | within 15 days after each vaccination | Mean CD4+ T-cell counts over time |
| 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'. |
| 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'. |
| 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'. |
| 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. |
| 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'. |
| Number of Participants With AESIs | within 75 weeks | Occurrence, relationship to the trial vaccine, and intensity of any adverse event of special interest (AESI) |
| 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'. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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'. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Subjects were screened and enrolled at 12 sites in the US
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (Standard Regimen) 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 | 27 |
| Group 2 (Double Dose Regimen) 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 | 29 |
| Group 3 (Booster Regimen) 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 | 31 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | incarcerated | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Group 2 (Double Dose Regimen) | Total | Group 1 (Standard Regimen) | Group 3 (Booster Regimen) |
|---|---|---|---|---|
| Age, Continuous | 33.1 years STANDARD_DEVIATION 6.67 | 35 years STANDARD_DEVIATION 6.68 | 35.1 years STANDARD_DEVIATION 7.66 | 36.6 years STANDARD_DEVIATION 5.43 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 18 Participants | 50 Participants | 16 Participants | 16 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants | 12 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 25 Participants | 75 Participants | 22 Participants | 28 Participants |
| Race/Ethnicity, Customized Oriental/Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White/Caucasian | 10 Participants | 34 Participants | 10 Participants | 14 Participants |
| Region of Enrollment United States | 29 participants | 87 participants | 27 participants | 31 participants |
| Sex: Female, Male Female | 5 Participants | 12 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 24 Participants | 75 Participants | 23 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 29 | 0 / 31 |
| other Total, other adverse events | 5 / 27 | 6 / 29 | 10 / 31 |
| serious Total, serious adverse events | 0 / 27 | 0 / 29 | 2 / 31 |
Outcome results
Primary
Number of Participants With SAEs
Occurrence, relationship and intensity of any serious AE (SAE)
Time frame: within 75 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 (Standard Regimen) | Number of Participants With SAEs | Any SAE with intensity >= Grade 3 | 0 Participants |
| Group 1 (Standard Regimen) | Number of Participants With SAEs | Any SAE | 0 Participants |
| Group 1 (Standard Regimen) | Number of Participants With SAEs | Any SAE assessed as related to vaccine | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With SAEs | Any SAE with intensity >= Grade 3 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With SAEs | Any SAE | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With SAEs | Any SAE assessed as related to vaccine | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With SAEs | Any SAE | 2 Participants |
| Group 3 (Booster Regimen) | Number of Participants With SAEs | Any SAE assessed as related to vaccine | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With SAEs | Any SAE with intensity >= Grade 3 | 2 Participants |
Secondary
CD4+ T Cell Counts
Mean CD4+ T-cell counts over time
Time frame: within 15 days after each vaccination
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (Standard Regimen) | CD4+ T Cell Counts | Screening | 304.9 CD4 count (cells/µL) | Standard Deviation 104.77 |
| Group 1 (Standard Regimen) | CD4+ T Cell Counts | Week 2 | 337.4 CD4 count (cells/µL) | Standard Deviation 118.18 |
| Group 1 (Standard Regimen) | CD4+ T Cell Counts | Week 6 | 319.1 CD4 count (cells/µL) | Standard Deviation 117.91 |
| Group 1 (Standard Regimen) | CD4+ T Cell Counts | Week 14 | NA CD4 count (cells/µL) | — |
| Group 2 (Double Dose Regimen) | CD4+ T Cell Counts | Week 14 | NA CD4 count (cells/µL) | — |
| Group 2 (Double Dose Regimen) | CD4+ T Cell Counts | Screening | 295.3 CD4 count (cells/µL) | Standard Deviation 111.1 |
| Group 2 (Double Dose Regimen) | CD4+ T Cell Counts | Week 6 | 365.4 CD4 count (cells/µL) | Standard Deviation 197.04 |
| Group 2 (Double Dose Regimen) | CD4+ T Cell Counts | Week 2 | 357.0 CD4 count (cells/µL) | Standard Deviation 157.87 |
| Group 3 (Booster Regimen) | CD4+ T Cell Counts | Week 14 | 351.9 CD4 count (cells/µL) | Standard Deviation 114.53 |
| Group 3 (Booster Regimen) | CD4+ T Cell Counts | Week 2 | 335.7 CD4 count (cells/µL) | Standard Deviation 111.11 |
| Group 3 (Booster Regimen) | CD4+ T Cell Counts | Week 6 | 345.0 CD4 count (cells/µL) | Standard Deviation 96.22 |
| Group 3 (Booster Regimen) | CD4+ T Cell Counts | Screening | 349.6 CD4 count (cells/µL) | Standard Deviation 133.71 |
Secondary
ELISA GMT 2 Weeks Following the Last Vaccination
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)
Population: Per-protocol Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 (Standard Regimen) | ELISA GMT 2 Weeks Following the Last Vaccination | 552.2 Titer |
| Group 2 (Double Dose Regimen) | ELISA GMT 2 Weeks Following the Last Vaccination | 846.1 Titer |
| Group 3 (Booster Regimen) | ELISA GMT 2 Weeks Following the Last Vaccination | 1591.2 Titer |
95% CI: [0.2, 0.603]
95% CI: [0.285, 0.992]
Secondary
ELISA GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))
GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.
Time frame: Week 6
Population: Per-protocol Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 (Standard Regimen) | ELISA GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) | 644.6 Titer |
| Group 2 (Double Dose Regimen) | ELISA GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) | 846.1 Titer |
95% CI: [0.385, 1.507]
Secondary
ELISA GMT During Follow-up
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)
Population: Per-protocol Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 (Standard Regimen) | ELISA GMT During Follow-up | Week 30/38 | 34.6 Titer |
| Group 1 (Standard Regimen) | ELISA GMT During Follow-up | Week 56/64 | 25.2 Titer |
| Group 2 (Double Dose Regimen) | ELISA GMT During Follow-up | Week 30/38 | 30.8 Titer |
| Group 2 (Double Dose Regimen) | ELISA GMT During Follow-up | Week 56/64 | 27.5 Titer |
| Group 3 (Booster Regimen) | ELISA GMT During Follow-up | Week 30/38 | 143.3 Titer |
| Group 3 (Booster Regimen) | ELISA GMT During Follow-up | Week 56/64 | 116.2 Titer |
95% CI: [1.241, 13.793]
95% CI: [1.365, 15.558]
95% CI: [0.066, 0.699]
95% CI: [0.072, 0.782]
Secondary
Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points
GMTs based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.
Time frame: within 64 weeks
Population: Per-protocol Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 (Standard Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 4 | 40.0 Titer |
| Group 1 (Standard Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 14 | NA Titer |
| Group 1 (Standard Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 12 | NA Titer |
| Group 1 (Standard Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 0 | 1.5 Titer |
| Group 1 (Standard Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 56/64 | 25.2 Titer |
| Group 1 (Standard Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 30/38 | 34.6 Titer |
| Group 1 (Standard Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 6 | 552.2 Titer |
| Group 2 (Double Dose Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 12 | NA Titer |
| Group 2 (Double Dose Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 0 | 1.2 Titer |
| Group 2 (Double Dose Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 4 | 47.1 Titer |
| Group 2 (Double Dose Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 6 | 846.1 Titer |
| Group 2 (Double Dose Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 14 | NA Titer |
| Group 2 (Double Dose Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 30/38 | 30.8 Titer |
| Group 2 (Double Dose Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 56/64 | 27.5 Titer |
| Group 3 (Booster Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 14 | 1591.2 Titer |
| Group 3 (Booster Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 4 | 41.8 Titer |
| Group 3 (Booster Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 56/64 | 116.2 Titer |
| Group 3 (Booster Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 30/38 | 143.3 Titer |
| Group 3 (Booster Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 12 | 193.1 Titer |
| Group 3 (Booster Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 6 | 726.1 Titer |
| Group 3 (Booster Regimen) | Geometric Mean Titers (GMT) Measured by Enzyme-linked Immunosorbent Assay (ELISA) at All Immunogenicity Sampling Points | Week 0 | 1.8 Titer |
95% CI: [0.258, 2.8]
95% CI: [0.319, 1.333]
95% CI: [0.291, 4.352]
95% CI: [0.22, 3.819]
95% CI: [0.292, 3.741]
95% CI: [0.598, 2.892]
Secondary
GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points
GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.
Time frame: within 64 weeks
Population: Per-protocol Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 (Standard Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 6 | 78.9 Titer |
| Group 1 (Standard Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 56/64 | 6.2 Titer |
| Group 1 (Standard Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 14 | NA Titer |
| Group 1 (Standard Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 12 | NA Titer |
| Group 1 (Standard Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 4 | 3.9 Titer |
| Group 1 (Standard Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 0 | NA Titer |
| Group 1 (Standard Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 30/38 | 6.2 Titer |
| Group 2 (Double Dose Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 56/64 | 10.6 Titer |
| Group 2 (Double Dose Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 0 | NA Titer |
| Group 2 (Double Dose Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 4 | 4.8 Titer |
| Group 2 (Double Dose Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 6 | 100.3 Titer |
| Group 2 (Double Dose Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 12 | NA Titer |
| Group 2 (Double Dose Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 14 | NA Titer |
| Group 2 (Double Dose Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 30/38 | 11.5 Titer |
| Group 3 (Booster Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 0 | 1.2 Titer |
| Group 3 (Booster Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 14 | 281.1 Titer |
| Group 3 (Booster Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 4 | 10.1 Titer |
| Group 3 (Booster Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 56/64 | 45.3 Titer |
| Group 3 (Booster Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 30/38 | 41.5 Titer |
| Group 3 (Booster Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 12 | 35.5 Titer |
| Group 3 (Booster Regimen) | GMTs Measured by Plaque Reduction Neutralization Test (PRNT) at All Immunogenicity Sampling Points | Week 6 | 95.9 Titer |
95% CI: [0.333, 2.038]
95% CI: [0.41, 1.508]
95% CI: [0.187, 1.536]
95% CI: [0.203, 1.716]
95% CI: [0.972, 6.731]
95% CI: [0.612, 2.412]
Secondary
Number of Participants With AESIs
Occurrence, relationship to the trial vaccine, and intensity of any adverse event of special interest (AESI)
Time frame: within 75 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 (Standard Regimen) | Number of Participants With AESIs | Any AESI with intensity >= Grade 3 | 0 Participants |
| Group 1 (Standard Regimen) | Number of Participants With AESIs | Any AESI | 0 Participants |
| Group 1 (Standard Regimen) | Number of Participants With AESIs | Any AESI assessed as related to vaccine | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With AESIs | Any AESI with intensity >= Grade 3 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With AESIs | Any AESI | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With AESIs | Any AESI assessed as related to vaccine | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With AESIs | Any AESI | 1 Participants |
| Group 3 (Booster Regimen) | Number of Participants With AESIs | Any AESI assessed as related to vaccine | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With AESIs | Any AESI with intensity >= Grade 3 | 0 Participants |
Secondary
Number of Participants With Related Grade >=3 Adverse Events
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
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Standard Regimen) | Number of Participants With Related Grade >=3 Adverse Events | 4 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Related Grade >=3 Adverse Events | 5 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Related Grade >=3 Adverse Events | 3 Participants |
Secondary
Number of Participants With Solicited General AEs
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
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Headache, Grade 2 | 1 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Pyrexia, Grade 2 | 1 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Pyrexia, Grade 3 | 0 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Headache, Grade 1 | 8 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Pyrexia, Grade 1 | 0 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Headache, Grade 3 | 0 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Myalgia, Grade 1 | 6 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Myalgia, Grade 2 | 2 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Myalgia, Grade 3 | 1 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Chills, Grade 1 | 4 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Chills, Grade 2 | 2 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Chills, Grade 3 | 1 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Nausea, Grade 1 | 3 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Nausea, Grade 2 | 3 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Nausea, Grade 3 | 0 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Fatigue, Grade 1 | 5 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Fatigue, Grade 2 | 2 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited General AEs | Fatigue, Grade 3 | 2 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Fatigue, Grade 3 | 2 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Pyrexia, Grade 1 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Chills, Grade 1 | 4 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Nausea, Grade 1 | 4 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Pyrexia, Grade 2 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Nausea, Grade 3 | 2 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Fatigue, Grade 1 | 4 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Pyrexia, Grade 3 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Chills, Grade 2 | 2 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Fatigue, Grade 2 | 5 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Headache, Grade 1 | 5 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Myalgia, Grade 3 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Nausea, Grade 2 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Headache, Grade 2 | 3 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Myalgia, Grade 2 | 6 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Chills, Grade 3 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Headache, Grade 3 | 2 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited General AEs | Myalgia, Grade 1 | 6 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Headache, Grade 3 | 1 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Myalgia, Grade 1 | 8 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Myalgia, Grade 2 | 4 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Nausea, Grade 3 | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Myalgia, Grade 3 | 1 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Fatigue, Grade 3 | 1 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Chills, Grade 1 | 5 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Chills, Grade 2 | 1 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Fatigue, Grade 1 | 5 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Chills, Grade 3 | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Pyrexia, Grade 1 | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Pyrexia, Grade 2 | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Nausea, Grade 1 | 4 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Pyrexia, Grade 3 | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Headache, Grade 1 | 6 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Headache, Grade 2 | 3 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Nausea, Grade 2 | 2 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited General AEs | Fatigue, Grade 2 | 5 Participants |
Secondary
Number of Participants With Solicited Local Adverse Events
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
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Induration, Grade 1 | 7 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Erythema, Grade 3 | 0 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pruritus, Grade 1 | 7 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Swelling, Grade 3 | 0 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Swelling, Grade 2 | 1 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pruritus, Grade 3 | 1 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pain, Grade 3 | 2 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Swelling, Grade 1 | 9 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pruritus, Grade 2 | 4 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Induration, Grade 3 | 0 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Erythema, Grade 1 | 7 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pain, Grade 2 | 10 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Induration, Grade 2 | 1 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Erythema, Grade 2 | 1 Participants |
| Group 1 (Standard Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pain, Grade 1 | 5 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Induration, Grade 3 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pain, Grade 1 | 4 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pain, Grade 2 | 11 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pain, Grade 3 | 4 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Erythema, Grade 1 | 11 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Erythema, Grade 2 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Erythema, Grade 3 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pruritus, Grade 3 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Swelling, Grade 1 | 9 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Swelling, Grade 2 | 1 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Swelling, Grade 3 | 0 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Induration, Grade 1 | 5 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Induration, Grade 2 | 1 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pruritus, Grade 2 | 2 Participants |
| Group 2 (Double Dose Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pruritus, Grade 1 | 6 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Induration, Grade 3 | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Swelling, Grade 3 | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Erythema, Grade 2 | 3 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pain, Grade 2 | 10 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Induration, Grade 1 | 9 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Erythema, Grade 1 | 15 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pain, Grade 1 | 11 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Induration, Grade 2 | 1 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pruritus, Grade 3 | 0 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pain, Grade 3 | 1 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Swelling, Grade 1 | 9 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pruritus, Grade 2 | 3 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Pruritus, Grade 1 | 15 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Swelling, Grade 2 | 4 Participants |
| Group 3 (Booster Regimen) | Number of Participants With Solicited Local Adverse Events | Injection Site Erythema, Grade 3 | 0 Participants |
Secondary
Number of Unsolicited Non-serious Adverse Events: Intensity
Occurrence of unsolicited non-serious AEs by Intensity
Time frame: within 29 days after any vaccination
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (Standard Regimen) | Number of Unsolicited Non-serious Adverse Events: Intensity | Severe | 1 events |
| Group 1 (Standard Regimen) | Number of Unsolicited Non-serious Adverse Events: Intensity | Moderate | 1 events |
| Group 1 (Standard Regimen) | Number of Unsolicited Non-serious Adverse Events: Intensity | Mild | 4 events |
| Group 2 (Double Dose Regimen) | Number of Unsolicited Non-serious Adverse Events: Intensity | Severe | 0 events |
| Group 2 (Double Dose Regimen) | Number of Unsolicited Non-serious Adverse Events: Intensity | Mild | 7 events |
| Group 2 (Double Dose Regimen) | Number of Unsolicited Non-serious Adverse Events: Intensity | Moderate | 0 events |
| Group 3 (Booster Regimen) | Number of Unsolicited Non-serious Adverse Events: Intensity | Severe | 0 events |
| Group 3 (Booster Regimen) | Number of Unsolicited Non-serious Adverse Events: Intensity | Moderate | 6 events |
| Group 3 (Booster Regimen) | Number of Unsolicited Non-serious Adverse Events: Intensity | Mild | 9 events |
Secondary
Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination
Occurrence of unsolicited non-serious AEs by relationship to study vaccine
Time frame: within 29 days after any vaccination
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (Standard Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Probable | 0 events |
| Group 1 (Standard Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Unlikely | 1 events |
| Group 1 (Standard Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Definite | 0 events |
| Group 1 (Standard Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Unrelated/None | 4 events |
| Group 1 (Standard Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Possible | 1 events |
| Group 2 (Double Dose Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Unrelated/None | 4 events |
| Group 2 (Double Dose Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Probable | 0 events |
| Group 2 (Double Dose Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Possible | 1 events |
| Group 2 (Double Dose Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Definite | 0 events |
| Group 2 (Double Dose Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Unlikely | 2 events |
| Group 3 (Booster Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Definite | 0 events |
| Group 3 (Booster Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Unlikely | 1 events |
| Group 3 (Booster Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Possible | 0 events |
| Group 3 (Booster Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Probable | 1 events |
| Group 3 (Booster Regimen) | Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination | Unrelated/None | 13 events |
Secondary
Percentage of Participants With Seroconversion by ELISA
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
Population: Per-protocol Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 30/38 | 77.8 percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 56/64 | 66.7 percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 12 | NA percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 4 | 75.0 percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 14 | NA percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 6 | 100.0 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 4 | 82.6 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 30/38 | 72.7 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 6 | 100.0 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 12 | NA percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 56/64 | 68.2 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 14 | NA percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 56/64 | 83.3 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 4 | 69.2 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 6 | 92.3 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 12 | 84.6 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 14 | 100.0 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by ELISA | Week 30/38 | 83.3 percentage of subjects |
95% CI: [-32.8, 22.2]
95% CI: [-25.1, 10.1]
95% CI: [-34.1, 17.9]
95% CI: [-16.8, 16.3]
95% CI: [-24.5, 32.6]
95% CI: [-31.5, 29.2]
Secondary
Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Last Vaccination
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)
Population: Per-protocol Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Last Vaccination | 100.0 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Last Vaccination | 100.0 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Last Vaccination | 100.0 percentage of subjects |
95% CI: [-17.1, 13.4]
95% CI: [-16.2, 13.4]
Secondary
Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))
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
Population: Per-protocol Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) | 95.7 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by ELISA 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) | 100.0 percentage of subjects |
95% CI: [-15.2, 11.6]
Secondary
Percentage of Participants With Seroconversion by ELISA During Follow-up
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)
Population: Per-protocol Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by ELISA During Follow-up | Week 30/38 | 77.8 percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by ELISA During Follow-up | Week 56/64 | 66.7 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by ELISA During Follow-up | Week 30/38 | 72.7 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by ELISA During Follow-up | Week 56/64 | 68.2 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by ELISA During Follow-up | Week 30/38 | 83.3 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by ELISA During Follow-up | Week 56/64 | 83.3 percentage of subjects |
95% CI: [-19.6, 33]
95% CI: [-11, 44.4]
95% CI: [-35.6, 14.3]
95% CI: [-40.5, 10.5]
Secondary
Percentage of Participants With Seroconversion by PRNT
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
Population: Per-protocol Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 4 | 60.0 percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 6 | 100.0 percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 12 | NA percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 14 | NA percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 30/38 | 72.2 percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 56/64 | 66.7 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 56/64 | 72.7 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 4 | 69.6 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 14 | NA percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 30/38 | 81.8 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 6 | 100.0 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 12 | NA percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 6 | 96.2 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 12 | 96.2 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 56/64 | 95.8 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 14 | 100.0 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 4 | 80.8 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by PRNT | Week 30/38 | 91.7 percentage of subjects |
95% CI: [-38.4, 20.3]
95% CI: [-16.8, 16.3]
95% CI: [-38.4, 17.6]
95% CI: [-35.6, 23.7]
95% CI: [-7.7, 47.8]
95% CI: [-20.5, 13.4]
Secondary
Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Last Vaccination
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)
Population: Per-protocol Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Last Vaccination | 100.0 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Last Vaccination | 100.0 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Last Vaccination | 100.0 percentage of subjects |
95% CI: [-17.1, 13.4]
95% CI: [-16.2, 13.4]
Secondary
Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))
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
Population: Per-protocol Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) | 97.8 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by PRNT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) | 100.0 percentage of subjects |
95% CI: [-12, 13.2]
Secondary
Percentage of Participants With Seroconversion by PRNT During Follow-up
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)
Population: Per-protocol Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by PRNT During Follow-up | Week 30/38 | 72.2 percentage of subjects |
| Group 1 (Standard Regimen) | Percentage of Participants With Seroconversion by PRNT During Follow-up | Week 56/64 | 66.7 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by PRNT During Follow-up | Week 30/38 | 81.8 percentage of subjects |
| Group 2 (Double Dose Regimen) | Percentage of Participants With Seroconversion by PRNT During Follow-up | Week 56/64 | 72.7 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by PRNT During Follow-up | Week 30/38 | 91.7 percentage of subjects |
| Group 3 (Booster Regimen) | Percentage of Participants With Seroconversion by PRNT During Follow-up | Week 56/64 | 95.8 percentage of subjects |
95% CI: [-4.5, 45.8]
95% CI: [5.8, 55.4]
95% CI: [-33, 11.7]
95% CI: [-46.7, -1]
Secondary
PRNT GMT 2 Weeks Following the Last Vaccination
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)
Population: Per-protocol Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 (Standard Regimen) | PRNT GMT 2 Weeks Following the Last Vaccination | 78.9 Titer |
| Group 2 (Double Dose Regimen) | PRNT GMT 2 Weeks Following the Last Vaccination | 100.3 Titer |
| Group 3 (Booster Regimen) | PRNT GMT 2 Weeks Following the Last Vaccination | 281.1 Titer |
95% CI: [0.146, 0.542]
95% CI: [0.178, 0.718]
Secondary
PRNT GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined))
GMTs based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.
Time frame: Week 6
Population: Per-protocol Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 (Standard Regimen) | PRNT GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) | 88.1 Titer |
| Group 2 (Double Dose Regimen) | PRNT GMT 2 Weeks Following the Second Vaccination (Group 2 Compared to Group 1 and Group 3 (Combined)) | 100.3 Titer |
95% CI: [0.48, 1.606]
Secondary
PRNT GMT During Follow-up
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)
Population: Per-protocol Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 (Standard Regimen) | PRNT GMT During Follow-up | Week 30/38 | 6.2 Titer |
| Group 1 (Standard Regimen) | PRNT GMT During Follow-up | Week 56/64 | 6.2 Titer |
| Group 2 (Double Dose Regimen) | PRNT GMT During Follow-up | Week 30/38 | 11.5 Titer |
| Group 2 (Double Dose Regimen) | PRNT GMT During Follow-up | Week 56/64 | 10.6 Titer |
| Group 3 (Booster Regimen) | PRNT GMT During Follow-up | Week 30/38 | 41.5 Titer |
| Group 3 (Booster Regimen) | PRNT GMT During Follow-up | Week 56/64 | 45.3 Titer |
95% CI: [2.493, 18.15]
95% CI: [2.693, 19.649]
95% CI: [0.115, 0.672]
95% CI: [0.1, 0.541]