Smallpox
Conditions
Brief summary
The study was preformed to evaluate the persistence of antibodies following vaccination with MVA-BN and to assess the immunological memory response induced by a booster vaccination with MVA-BN in subjects two years after their participation in trial POX-MVA-005 (NCT00316524) in which they had received one or two doses of MVA-BN.
Interventions
BIOLOGICALIMVAMUNE
1x 10E8\_TCID50
PROCEDUREBlood Draw Only
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Bavarian Nordic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Groups 1 and 2 (first consenting 75 subjects in each group to be vaccinated) * Male and female subjects having participated in Group 1 or 2 of the study POX-MVA-005 who completed the trial according to protocol. * Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine or serum pregnancy test within 24 hours prior to vaccination. * Women of childbearing potential must have used an acceptable method of contraception for 30 days prior to the vaccination, must agree to use an acceptable method of contraception during the study, and must not become pregnant for at least 28 days after the vaccination. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products.) * Read, signed and dated informed consent document after being advised of the risks and benefits of the study in a language understood by the subject signed, and prior to performance of any study specific procedure. * Troponin I within normal institutional limits. * White blood cells ≥ 2,500/mm3 and \<= 11,000/mm3. * Absolute neutrophil count within normal limits. * Negative urine glucose by dipstick or urinalysis. * Hemoglobin within the laboratory reference ranges (unless the investigator considers the deviation to be not clinically significant). * Platelets 100 - 440/nL. * Adequate renal function defined as: 1. Serum creatinine without clinically significant findings. 2. Urine protein \<= 30 mg/dL or none or trace proteinuria (by urinalysis or dip stick). * Adequate hepatic function defined as: 1. Total bilirubin \<= 1.5 x upper limit of normal (ULN) in the absence of other evidence of significant liver disease (healthy subjects without clinical disease; Morbus Meulengracht can be included). 2. AST (SGOT), ALT (SGPT), alkaline phosphatase without clinically significant findings. * Electrocardiogram (ECG) without clinically relevant abnormal 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). Group 4 (all subjects) and Groups 1 and 2 (subjects N \> 75): blood draw only * Male and female subjects having participated in the study POX-MVA-005 who completed the trial according to protocol. * Read, signed and dated informed consent document after being advised of the risks and benefits of the blood draw in a language understood by the subject signed, and prior to performance of the blood draw.
Exclusion criteria
Groups 1 and 2 (first consenting 75 subjects in each group to be vaccinated) * Participation in another study with a smallpox vaccine after the POX-MVA-005 study. * Pregnant or breast-feeding women. * Uncontrolled serious infection i.e. not responding to antimicrobial therapy. * History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject. * History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid replacement are not excluded. * Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment. * History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure. Subjects with history of skin cancer must not be vaccinated at the previous site of cancer. * History or clinical manifestation of clinically significant and severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders. * Clinically significant mental disorder not adequately controlled by medical treatment. * Any condition which might interfere with study objectives or would limit the subject's ability to complete the study or to be compliant in the opinion of the investigator. * History of coronary heart disease, myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor. * History of an immediate family member (father, mother, brother, or sister) who died due to ischemic heart disease before age 50 years. * Twenty percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool. (http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof). * History of intravenous drug abuse. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. tris (hydroxymethyl)-amino methane, chicken embryo fibroblast proteins, aminoglycosides (gentamycin). * History of any anaphylactic shock or severe allergic reaction requiring immediate treatment. * Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior or after study vaccination. * Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior or after study vaccination. * Chronic administration (defined as more than 14 days) of \> 5 mg prednisone (or equivalent) per day or any other immune-modifying drugs during a period starting from three months prior to administration of the vaccine and ending at study conclusion (Visit 4). * Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy. * Administration or planned administration of immunoglobulins and/or any blood products during a period starting from 3 months prior to administration of the vaccine and ending at study conclusion. * Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding administration of the study vaccine, or planned administration of such a drug during the study period. Group 4 (all subjects) and Groups 1 and 2 (subjects N \> 75): blood draw only * Participation in another study with a smallpox vaccine after the POX-MVA-005 study. * Any condition which might interfere with a blood draw.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Individual Peak Booster Rate by ELISA (Percentage of Participants) | within 4 weeks | Booster rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual Peak booster rate is based on the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Percentages based on number of subjects with data available. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ELISA GMT | within 26 weeks | Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Individual peak is defined as the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Titers below the detection limit are included with a value of '1'. |
| Booster Rate by PRNT (Percentage of Participants) | within 26 weeks | Booster rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (6) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual Peak booster rate is based on the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Percentages based on number of subjects with data available. |
| PRNT GMT | within 26 weeks | Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Individual peak is defined as the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Titers below the detection limit are included with a value of '1'. |
| Correlation PRNT vs ELISA Titers | within 26 weeks | Pearson Correlation Coefficient between the log10 transformed PRNT titers and the log10 transformed ELISA titers |
| Booster Rate by ELISA (Percentage of Participants) | within 26 weeks | Booster rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available. |
| Number of Participants With Unsolicited Non-serious Adverse Events | within 29 days after any vaccination | Number of participants with any, grade \>=3, and related non-serious unsolicited adverse events |
| Number of Participants With Related Grade >= 3 Unsolicited Adverse Events | within 29 days after vaccination | Number of participants with Grade \>=3 Unsolicited Adverse Event probably, possibly, or definitely related to the study vaccine |
| Number of Participants With Solicited Local Adverse Events | within 8 days after vaccination | Number of participants with and intensity of solicited local AEs (pain, erythema, swelling, induration, and pruritis). Percentages based on subjects with a completed diary card. |
| Number of Participants With Solicited General Adverse Events | within 8 days after vaccination | Number of participants with solicited general AEs (body temperature increased, headache, myalgia, nausea, and fatigue): Intensity and relationship to vaccination. Percentages based on subjects with a completed diary card. |
| Number of Participants With Related Serious Adverse Events | within 26 weeks | Number of participants with Serious Adverse Events (SAEs) probably, possibly or definitely related to the trial vaccine |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose Group 1 Initially Vaccinia Naive Subjects 2 doses of MVA-BN in prior study (POX-MVA-005)
1 booster dose of MVA-BN (POX-MVA-023) IMVAMUNE: 1x 10E8\_TCID50 | 92 |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose Group 2 Initially Vaccinia Naive Subjects 1 dose of MVA-BN and 1x Placebo in prior study (POX-MVA-005)
1 booster dose of MVA-BN (POX-MVA-023) IMVAMUNE: 1x 10E8\_TCID50 | 91 |
| Vaccinia Experienced, Boosted, Blood Draw Only Group 4 Vaccinia Experienced
1 booster dose of MVA-BN in prior study (POX-MVA-005) Blood draw, Screening Visit only (POX-MVA-023) | 121 |
| Total | 304 |
Baseline characteristics
| Characteristic | Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Vaccinia Experienced, Boosted, Blood Draw Only | Total |
|---|---|---|---|---|
| Age, Continuous | 27.7 years STANDARD_DEVIATION 5.8 | 27.7 years STANDARD_DEVIATION 4.5 | 44.9 years STANDARD_DEVIATION 6.6 | 34.6 years STANDARD_DEVIATION 10.2 |
| ELISA Long-Term Persistence | 23.33 Titer | 6.20 Titer | 134.65 Titer | 31.52 Titer |
| PRNT Long-Term Persistence | 1.26 Titer | 1.05 Titer | 10.28 Titer | 2.75 Titer |
| Sex: Female, Male Female | 50 Participants | 55 Participants | 67 Participants | 172 Participants |
| Sex: Female, Male Male | 42 Participants | 36 Participants | 54 Participants | 132 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 77 |
| other Total, other adverse events | 35 / 75 | 25 / 77 |
| serious Total, serious adverse events | 2 / 75 | 0 / 77 |
Outcome results
Primary
Individual Peak Booster Rate by ELISA (Percentage of Participants)
Booster rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual Peak booster rate is based on the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Percentages based on number of subjects with data available.
Time frame: within 4 weeks
Population: Full Analysis Set/ Booster Set i.e., all subjects having received a booster dose in POX-MVA-023. Thus, Group 4 is not included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Individual Peak Booster Rate by ELISA (Percentage of Participants) | 100.0 percentage of subjects |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Individual Peak Booster Rate by ELISA (Percentage of Participants) | 100.0 percentage of subjects |
Secondary
Booster Rate by ELISA (Percentage of Participants)
Booster rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Time frame: within 26 weeks
Population: Full Analysis Set/ Booster Set i.e., all subjects having received a booster dose in POX-MVA-023. Thus, Group 4 is not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Booster Rate by ELISA (Percentage of Participants) | Week 1 | 100.0 percentage of subjects |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Booster Rate by ELISA (Percentage of Participants) | Week 2 | 100.0 percentage of subjects |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Booster Rate by ELISA (Percentage of Participants) | Week 4 | 100.0 percentage of subjects |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Booster Rate by ELISA (Percentage of Participants) | Week 26 | 98.6 percentage of subjects |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Booster Rate by ELISA (Percentage of Participants) | Week 26 | 100.0 percentage of subjects |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Booster Rate by ELISA (Percentage of Participants) | Week 1 | 98.7 percentage of subjects |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Booster Rate by ELISA (Percentage of Participants) | Week 4 | 100.0 percentage of subjects |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Booster Rate by ELISA (Percentage of Participants) | Week 2 | 100.0 percentage of subjects |
Secondary
Booster Rate by PRNT (Percentage of Participants)
Booster rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT) is defined as the percentage of subjects with an appearance of antibody titers ≥ detection limit (6) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual Peak booster rate is based on the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Percentages based on number of subjects with data available.
Time frame: within 26 weeks
Population: Full Analysis Set/ Booster Set i.e., all subjects having received a booster dose in POX-MVA-023. Thus, Group 4 is not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Booster Rate by PRNT (Percentage of Participants) | Week 2 | 98.7 percentage of subjects |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Booster Rate by PRNT (Percentage of Participants) | Individual peak | 98.7 percentage of subjects |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Booster Rate by PRNT (Percentage of Participants) | Week 4 | 94.6 percentage of subjects |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Booster Rate by PRNT (Percentage of Participants) | Week 26 | 88.7 percentage of subjects |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Booster Rate by PRNT (Percentage of Participants) | Week 1 | 92.0 percentage of subjects |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Booster Rate by PRNT (Percentage of Participants) | Week 26 | 76.6 percentage of subjects |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Booster Rate by PRNT (Percentage of Participants) | Week 1 | 85.7 percentage of subjects |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Booster Rate by PRNT (Percentage of Participants) | Week 2 | 96.1 percentage of subjects |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Booster Rate by PRNT (Percentage of Participants) | Week 4 | 90.9 percentage of subjects |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Booster Rate by PRNT (Percentage of Participants) | Individual peak | 98.7 percentage of subjects |
Secondary
Correlation PRNT vs ELISA Titers
Pearson Correlation Coefficient between the log10 transformed PRNT titers and the log10 transformed ELISA titers
Time frame: within 26 weeks
Population: Full Analysis Set/ Booster Set i.e., all subjects having received a booster dose in POX-MVA-023. Thus, Group 4 is not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Correlation PRNT vs ELISA Titers | Week 1 | 0.591 Pearson correlation coefficient |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Correlation PRNT vs ELISA Titers | Week 2 | 0.491 Pearson correlation coefficient |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Correlation PRNT vs ELISA Titers | Week 4 | 0.476 Pearson correlation coefficient |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Correlation PRNT vs ELISA Titers | Week 26 | 0.568 Pearson correlation coefficient |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Correlation PRNT vs ELISA Titers | Week 26 | 0.550 Pearson correlation coefficient |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Correlation PRNT vs ELISA Titers | Week 1 | 0.690 Pearson correlation coefficient |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Correlation PRNT vs ELISA Titers | Week 4 | 0.592 Pearson correlation coefficient |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Correlation PRNT vs ELISA Titers | Week 2 | 0.655 Pearson correlation coefficient |
Secondary
ELISA GMT
Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Individual peak is defined as the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Titers below the detection limit are included with a value of '1'.
Time frame: within 26 weeks
Population: Full Analysis Set/ Booster Set i.e., all subjects having received a booster dose in POX-MVA-023. Thus, Group 4 is not included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | ELISA GMT | Screening | 24.23 Titer |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | ELISA GMT | Week 1 | 737.93 Titer |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | ELISA GMT | Week 2 | 1688.20 Titer |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | ELISA GMT | Week 4 | 1255.21 Titer |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | ELISA GMT | Individual peak | 1821.57 Titer |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | ELISA GMT | Week 26 | 461.78 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | ELISA GMT | Individual peak | 1723.74 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | ELISA GMT | Screening | 5.89 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | ELISA GMT | Week 4 | 1210.59 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | ELISA GMT | Week 1 | 490.33 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | ELISA GMT | Week 26 | 382.91 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | ELISA GMT | Week 2 | 1608.89 Titer |
Secondary
Number of Participants With Related Grade >= 3 Unsolicited Adverse Events
Number of participants with Grade \>=3 Unsolicited Adverse Event probably, possibly, or definitely related to the study vaccine
Time frame: within 29 days after vaccination
Population: Full Analysis Set/ Booster Set i.e., all subjects having received a booster dose in POX-MVA-023. Subjects from Group 4 had a blood draw at Screening only, did not receive a booster dose and adverse events were not monitored/assessed for this group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Related Grade >= 3 Unsolicited Adverse Events | 1 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Related Grade >= 3 Unsolicited Adverse Events | 0 Participants |
Secondary
Number of Participants With Related Serious Adverse Events
Number of participants with Serious Adverse Events (SAEs) probably, possibly or definitely related to the trial vaccine
Time frame: within 26 weeks
Population: Full Analysis Set/ Booster Set i.e., all subjects having received a booster dose in POX-MVA-023. Subjects from Group 4 had a blood draw at Screening only, did not receive a booster dose and adverse events were not monitored/assessed for this group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Related Serious Adverse Events | 0 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Related Serious Adverse Events | 0 Participants |
Secondary
Number of Participants With Solicited General Adverse Events
Number of participants with solicited general AEs (body temperature increased, headache, myalgia, nausea, and fatigue): Intensity and relationship to vaccination. Percentages based on subjects with a completed diary card.
Time frame: within 8 days after vaccination
Population: Full Analysis Set/ Booster Set i.e., all subjects having received a booster dose in POX-MVA-023. Subjects from Group 4 had a blood draw at Screening only, did not receive a booster dose and adverse events were not monitored/assessed for this group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Myalgia: Grade >=3 | 1 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Body temperature increased: Any | 3 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Myalgia: Related Grade >=3 | 1 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Headache: Grade >=3 | 2 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Nausea: Any | 6 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Nausea: Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Body temperature increased: Related Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Nausea: Related Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Headache: Related Grade >=3 | 1 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Fatigue: Any | 22 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Body temperature increased: Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Fatigue: Grade >=3 | 2 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Myalgia: Any | 17 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Fatigue: Related Grade >=3 | 2 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Headache: Any | 19 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Fatigue: Related Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Body temperature increased: Any | 4 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Body temperature increased: Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Body temperature increased: Related Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Headache: Any | 25 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Headache: Grade >=3 | 1 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Headache: Related Grade >=3 | 1 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Myalgia: Any | 19 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Myalgia: Grade >=3 | 1 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Myalgia: Related Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Nausea: Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Nausea: Related Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Fatigue: Any | 27 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Fatigue: Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited General Adverse Events | Nausea: Any | 12 Participants |
Secondary
Number of Participants With Solicited Local Adverse Events
Number of participants with and intensity of solicited local AEs (pain, erythema, swelling, induration, and pruritis). Percentages based on subjects with a completed diary card.
Time frame: within 8 days after vaccination
Population: Full Analysis Set/ Booster Set i.e., all subjects having received a booster dose in POX-MVA-023. Subjects from Group 4 had a blood draw at Screening only, did not receive a booster dose and adverse events were not monitored/assessed for this group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Pain: Any | 58 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Pain: Grade >=3 | 1 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Erythema: Any | 60 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Erythema: Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Swelling: Any | 51 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Swelling: Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Induration: Any | 58 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Induration: Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Pruritis: Any | 30 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Pruritis: Grade >=3 | 1 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Induration: Grade >=3 | 1 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Pain: Any | 64 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Swelling: Grade >=3 | 2 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Pain: Grade >=3 | 3 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Pruritis: Grade >=3 | 0 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Erythema: Any | 65 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Induration: Any | 58 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Erythema: Grade >=3 | 2 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Pruritis: Any | 36 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Solicited Local Adverse Events | Swelling: Any | 48 Participants |
Secondary
Number of Participants With Unsolicited Non-serious Adverse Events
Number of participants with any, grade \>=3, and related non-serious unsolicited adverse events
Time frame: within 29 days after any vaccination
Population: Full Analysis Set/ Booster Set i.e., all subjects having received a booster dose in POX-MVA-023. Subjects from Group 4 had a blood draw at Screening only, did not receive a booster dose and adverse events were not monitored/assessed for this group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Unsolicited Non-serious Adverse Events | Any event | 40 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Unsolicited Non-serious Adverse Events | Any event with intensity >= Grade 3 | 4 Participants |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | Number of Participants With Unsolicited Non-serious Adverse Events | Any event assessed as related to vaccine | 11 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Unsolicited Non-serious Adverse Events | Any event | 38 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Unsolicited Non-serious Adverse Events | Any event with intensity >= Grade 3 | 5 Participants |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | Number of Participants With Unsolicited Non-serious Adverse Events | Any event assessed as related to vaccine | 9 Participants |
Secondary
PRNT GMT
Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Individual peak is defined as the maximum post-Baseline antibody titer within 4 weeks (measurements at Weeks 1, 2, and 4). Titers below the detection limit are included with a value of '1'.
Time frame: within 26 weeks
Population: Full Analysis Set/ Booster Set i.e., all subjects having received a booster dose in POX-MVA-023. Thus, Group 4 is not included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | PRNT GMT | Screening | 1.23 Titer |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | PRNT GMT | Week 1 | 53.61 Titer |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | PRNT GMT | Week 2 | 125.26 Titer |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | PRNT GMT | Week 4 | 64.26 Titer |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | PRNT GMT | Individual Peak | 165.97 Titer |
| Initially Vaccinia Naive, 2 Dose Primed, 1 Booster Dose | PRNT GMT | Week 26 | 49.29 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | PRNT GMT | Individual Peak | 116.79 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | PRNT GMT | Screening | 1.06 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | PRNT GMT | Week 4 | 48.96 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | PRNT GMT | Week 1 | 28.58 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | PRNT GMT | Week 26 | 25.62 Titer |
| Initially Vaccinia Naive, 1 Dose Primed, 1 Booster Dose | PRNT GMT | Week 2 | 80.69 Titer |