18-42 Year Old Healthy Vaccinia-naïve Subjects
Conditions
Brief summary
To demonstrate the efficacy of MVA-BN® in terms of vaccinia-specific Plaque Reduction Neutralization Test (PRNT) antibody response and by showing that vaccination prior to administration of ACAM2000® results in an attenuated take.
Detailed description
To demonstrate the efficacy of MVA-BN® by assessing non-inferiority of MVA-BN® compared to ACAM2000® in terms of vaccinia-specific Plaque Reduction Neutralization Test (PRNT) antibody response at the Peak Visits (Day 42 for Group 1 and Day 28 for Group 2) and by showing that vaccination with MVA-BN® prior to administration of ACAM2000® results in an attenuation of take.
Interventions
BIOLOGICALMVA BN®
0.5 ml MVA BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
BIOLOGICALACAM2000®
0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.
Sponsors
US Army Medical Research Institute of Infectious Diseases
Bavarian Nordic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 42 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and female subjects, 18-42 years of age 2. The subject has read, signed and dated the Informed Consent, having been advised of the risks and benefits of the trial in a language understood by the subject and prior to performance of any trial specific procedure 3. Acceptable medical history by screening evaluation and physical examination 4. BMI greater or eaqual than 18.5 and smaller than 35 5. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at Screening and a negative urine or serum pregnancy test within 24 hours prior to each vaccination 6. WOCBP must have used an acceptable method of contraception for 28 days prior to the first vaccination, must agree to use an acceptable method of contraception during the trial, and must avoid becoming pregnant for at least 28 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products) 7. Human Immunodeficiency Virus (HIV) antibody negative, hepatitis B surface antigen negative and negative antibody test to hepatitis C virus 8. White blood cells greater or eaqual than 2500/mm3 and smaller than 11,000/mm3 9. Hemoglobin within normal limits 10. Platelets greater or eaqual than lower normal limits 11. Adequate renal function defined as a calculated Creatinine Clearance (CrCl) greater than 60 ml/min as estimated by the Cockcroft-Gault equation 12. Adequate hepatic function in the absence of other evidence of significant liver disease defined as: * Total bilirubin greater than 1.5 x Upper Limit Normal (ULN) * Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) greater than 1.5 x ULN * Alkaline Phosphatase (Alk Phos) greater than 1.5 x ULN 13. Troponin I smaller than 2 x ULN 14. 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, atrioventricular node block, QTc or PR prolongation, premature atrial contractions or other atrial arrhythmia, sustained ventricular arrhythmia, two premature ventricular contractions 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 defined as visible vaccination scar or documentation of smallpox vaccination or as reported by the subject 4. History of vaccination with any poxvirus-based vaccine 5. History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject 6. History of or active immunodeficiency or immunosuppression caused by acquired or congenital diseases or caused by ongoing treatments such as chronic (greater than 14 days) high-dose corticosteroids (smaller than 5 mg prednisone \[or equivalent\] per day applied systemically, i.e. parenterally or orally), chronic or planned treatment with steroid eye drops or ointment at time of enrollment or radiation, or immunosuppressive drugs; low-dose corticosteroid topical products and nasal sprays used sporadically, i.e. pro re nata (according to circumstances) are permissible 7. Having had radiation or X-ray treatment (not routine X-rays) within the last 3 months 8. Post organ and bone-marrow transplant subjects whether or not receiving chronic immunosuppressive therapy 9. Eye surgery within 4 weeks prior to trial vaccination 10. History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid hormone replacement are not excluded 11. Uncontrolled serious infection, i.e. not responding to antimicrobial therapy 12. History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision considered to have achieved cure. Subjects with history of skin cancer must not be vaccinated at the previous site of cancer 13. History of keloid formation 14. History or clinical manifestation of severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders 15. 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 16. Chest pain (that is diagnosed as cardiac related) or trouble breathing on exertion 17. 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 NOTE: This criterion applies only to subjects 20 years of age and older 18. History of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before the age of 50 years 19. Clinically significant psychological disorder not adequately controlled by medical treatment 20. Active or history of chronic alcohol abuse and/or intravenous and/or nasal drug abuse (within the past 6 months) 21. History of anaphylaxis or any severe allergic reaction or serious adverse reaction to a vaccine 22. Eczema of any degree or history of eczema 23. People with active atopic dermatitis (AD) \[characterized by pruritus, eczematous lesions, xerosis (dry skin), and lichenification (thickening of the skin and an increase in skin markings\] or with a history of AD 24. People with chronic exfoliative skin disorders/conditions 25. People with active current Varicella zoster, Herpes zoster, impetigo, uncontrolled acne, Darier's disease or any acute skin disorders of large magnitude, e.g., laceration requiring sutures 26. People with a tattoo that covers the vaccination injection area (preventing assessment of the area and interfering with a vaccination site photograph) 27. Having received any vaccinations or planned vaccinations with a live vaccine within 28 days prior to or after trial vaccination 28. Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior to or after trial vaccination 29. 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 trial conclusion 30. Use of any investigational or non-registered drug or vaccine other than the trial vaccines within 28 days preceding the first dose of the trial vaccine or planned administration of such a drug /vaccine during the trial period 31. Blood donation for the duration of the trial 32. Acute disease (illness with or without a fever) at the time of enrollment 33. Temperature ≥ 100.4°F (38.0°C) at the time of enrollment 34. Known household contacts with, or occupational exposure (other than minimal contact) to any of the following: * Pregnant women * Children \<12 months of age * People with eczema or a history of eczema * People with active AD or history of AD * People with chronic exfoliative skin disorders/conditions * People with active Varicella zoster, Herpes zoster, impetigo, uncontrolled acne, Darier's disease or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn with areas greater than 2×2 cm * People with active or recent immunodeficiency disease or use of immunosuppressive medications, for example: have or take medication for HIV, AIDS, leukemia, lymphoma, or chronic liver problem, have or take medication for Crohn's disease, lupus, arthritis, or other immune disease; have had radiation or X-ray treatment (not routine X-rays) within the last 3 months; have ever had a bone-marrow or organ transplant (or take medication for that ); or have another problem that requires steroids, prednisone or a cancer drug for treatment * People having had eye surgery within the last 4 weeks 35. Known allergy to MVA-BN® vaccine or any of its constituents, e.g. tris(hydroxymethyl)-amino methane, including known allergy to egg or aminoglycoside (gentamycin) 36. Known allergies to ACAM2000® and its diluents including polymyxin B sulfate, neomycin sulfate, and phenol 37. Known allergies to vaccinia immunoglobulin (VIG) including thimerosal or previous allergic reaction to immunoglobulins 38. Known allergies to cidofovir, sulfa drugs, or probenecid 39. Trial personnel
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT) at the Peak Visits | Day 42 for Group 1 and Day 28 for Group 2 | GMT based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of 1. |
| Maximum Lesion Area (MLA) in mm2 After Scarification With ACAM2000® | Day 6-8, 13-15 after 3rd Vaccination for Group 1 and Day 6-8, 13-15 after 1st vaccination for Group 2 | The MLA was defined as the maximum of two measurements: the lesion area measured on Day 6-8 (after scarification) or the lesion area measured on Day 13-15 (after scarification). This was measured using the SilhouetteConnect camera system, and confirmed by the Independent Take Review Committee (ITRC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-measured Lesion Diameter in mm at Day 13-15 After Scarification With ACAM2000 | Day 13-15 after ACAM2000 scarification | The lesion diameter at Day 13-15 was defined as the major lesion diameter measured on Day 13-15 (after scarification) |
| Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC) | Day 6-8 visit following ACAM2000 vaccination | Take was assessed as either full, partial, or absent take by the ITRC based on Day 6-8 evaluations following ACAM2000 vaccination using subject profiles that contained supportive data up to Day 14 following ACAM2000 vaccination (in accordance with the ITRC Charter). |
| Lesion Area in mm2 at Day 6-8 After Scarification With ACAM2000 | Day 6-8 after ACAM2000 scarification | Lesion area was measured by the Investigator using the SilhouetteConnect camera system and confirmed by the blinded ITRC. |
| Lesion Area in mm2 at Day 13-15 After Scarification With ACAM2000 | Day 13-15 after ACAM2000 scarification | Lesion area was measured by the Investigator using the SilhouetteConnect camera system and confirmed by the blinded ITRC. |
| Relationship to Vaccine of Any Serious Adverse Event (SAE) | Within 38 weeks for Group 1 and 30 weeks for Group 2 | Presentation of SAEs by relationship to study vaccine |
| Intensity of Any Serious Adverse Event (SAE) | Within 38 weeks for Group 1 and 30 weeks for Group 2 | Presentation of SAEs by intensity |
| Incidence of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis, i.e. Adverse Events of Special Interest (AESIs) | Within 38 weeks for Group 1 and 30 weeks for Group 2 | In this clinical trial, an AESI was defined as any cardiac sign or symptom developed since the first vaccination, any ECG changes determined to be clinically significant, or any cardiac enzyme results of Troponin I ≥ 2 x ULN. |
| Related Grade >=3 Adverse Events | within 29 days after vaccination | Incidence of any Grade 3 or 4 adverse events (AEs) possibly, probably, or definitely related to the vaccine. Pooled solicited (general only) and unsolicited AEs. |
| Relationship to Vaccine of Any Non-serious AEs | within 29 days after vaccination | Presentation of non-serious AEs by relationship to study vaccine |
| Intensity of Any Non-serious AEs | within 29 days after vaccination | Presentation of non-serious AEs by intensity |
| Investigator-measured Maximum Lesion Diameter (MLD) in mm After Scarification With ACAM2000 | Day 6-8 and Day 13-15 after ACAM2000 scarification | The MLD was defined as the largest major diameter measured across the lesion on Day 6-8 (after scarification) or Day 13-15 (after scarification) |
| Incidence of Lymphadenopathy | within 29 days after vaccination | Incidence of events of Lymphadenopathy. Pooled solicited and unsolicited events. |
| Solicited Local AEs: Intensity | within 15 days after vaccination | Incidence of solicited local AEs (pain, redness \[erythema\], swelling, induration, itching \[pruritus\]) |
| Major Lesion Size, Major Erythema, and Major Induration Diameter | Within 15 days after scarification with ACAM2000 | Daily measurement of major lesion size, major erythema, and major induration diameter (mm) based on physical appearance of vaccination site as documented in the memory aid. If the shape of the lesion, erythema \[excludes lymphangitis\], and induration observed was not round but rather asymmetrical, then the largest \[or major\] cross-sectional measurement was recorded. |
| GMTs at the Peak Visits and Individual Peak Measured by Vaccinia-specific ELISA | within 8 weeks (for both groups) | Peak Visit was defined as Day 42 for Group 1 and Day 28 for Group 2. Individual Peak was the maximum titer per subject from Visit 1 to Visit 7 (Week 8) in Group 1 and maximum titer from Visit 1 to Visit 6 (Week 8) in Group 2. Titers below the detection limit are included with a value of 1. |
| GMTs at the Individual Peak Measured by Vaccinia-specific PRNT | within 8 weeks (for both groups) | Individual Peak was the maximum titer per subject from Visit 1 to Visit 7 (Week 8) in Group 1 and maximum titer from Visit 1 to Visit 6 (Week 8) in Group 2. Titers below the detection limit are included with a value of 1. |
| GMTs as Measured by Vaccinia-specific ELISA | within 12 weeks | GMT based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'. |
| GMTs as Measured by Vaccinia-specific PRNT | within 12 weeks | GMT based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'. |
| PRNT Seroconversion Rates at Peak Visits | Group 1 at Week 6; Group 2 at Week 4 | Seroconversion rate based on PRNT. Seroconversion is defined as the appearance of antibody titers greater than or equal 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. |
| ELISA Seroconversion Rates at Peak Visits | Group 1 at Week 6; Group 2 at Week 4 | Seroconversion rate based on ELISA. Seroconversion is defined as the appearance of antibody titers greater than or equal 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. |
| Solicited General AEs | within 15 days after vaccination | Occurrence, intensity and relationship of solicited general AEs (body temperature \[fever\], headache, myalgia \[muscle pain\], chills, nausea, fatigue, malaise) |
| Investigator-measured Lesion Diameter in mm at Day 6-8 After Scarification With ACAM2000 | Day 6-8 after ACAM2000 scarification | The lesion diameter at Day 6-8 was defined as the major lesion diameter measured on Day 6-8 (after scarification) |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Two vaccinations; MVA BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA BN® vaccination (Day 56).
MVA BN®: 0.5 ml MVA BN® with a nominal titre of 1x10E8 TCID50, administered as a subcutaneous injection
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle. | 220 |
| Group 2 A single vaccination of ACAM2000® will be administered at Day 0.
ACAM2000®: 0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle. | 213 |
| Total | 433 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | multiple reasons | 10 | 7 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Withdrawal by Subject | 20 | 6 |
Baseline characteristics
| Characteristic | Group 1 | Total | Group 2 |
|---|---|---|---|
| Age, Continuous | 23.5 years STANDARD_DEVIATION 4.77 | 23.5 years STANDARD_DEVIATION 4.67 | 23.4 years STANDARD_DEVIATION 4.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 54 Participants | 94 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 166 Participants | 339 Participants | 173 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 14 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 26 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 48 Participants | 88 Participants | 40 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants | 35 Participants | 16 Participants |
| Race (NIH/OMB) White | 126 Participants | 262 Participants | 136 Participants |
| Region of Enrollment South Korea | 220 participants | 433 participants | 213 participants |
| Sex: Female, Male Female | 39 Participants | 68 Participants | 29 Participants |
| Sex: Female, Male Male | 181 Participants | 365 Participants | 184 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 220 | 0 / 208 | 0 / 196 | 0 / 213 |
| other Total, other adverse events | 95 / 220 | 63 / 208 | 79 / 196 | 88 / 213 |
| serious Total, serious adverse events | 2 / 220 | 0 / 208 | 3 / 196 | 3 / 213 |
Outcome results
Primary
Maximum Lesion Area (MLA) in mm2 After Scarification With ACAM2000®
The MLA was defined as the maximum of two measurements: the lesion area measured on Day 6-8 (after scarification) or the lesion area measured on Day 13-15 (after scarification). This was measured using the SilhouetteConnect camera system, and confirmed by the Independent Take Review Committee (ITRC).
Time frame: Day 6-8, 13-15 after 3rd Vaccination for Group 1 and Day 6-8, 13-15 after 1st vaccination for Group 2
Population: Per-protocol Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Maximum Lesion Area (MLA) in mm2 After Scarification With ACAM2000® | 0.0 mm2 |
| Group 2 | Maximum Lesion Area (MLA) in mm2 After Scarification With ACAM2000® | 76.0 mm2 |
95% CI: [96.6, 98.3]
Primary
Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT) at the Peak Visits
GMT based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of 1.
Time frame: Day 42 for Group 1 and Day 28 for Group 2
Population: Per-protocol Set for Immunogenicity
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 | Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT) at the Peak Visits | 153.5 Titer |
| Group 2 | Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT) at the Peak Visits | 79.3 Titer |
95% CI: [1.562, 2.397]
Secondary
ELISA Seroconversion Rates at Peak Visits
Seroconversion rate based on ELISA. Seroconversion is defined as the appearance of antibody titers greater than or equal 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: Group 1 at Week 6; Group 2 at Week 4
Population: Per-protocol Set for Immunogenicity
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | ELISA Seroconversion Rates at Peak Visits | 100 percentage of subjects |
| Group 2 | ELISA Seroconversion Rates at Peak Visits | 96.8 percentage of subjects |
Secondary
GMTs as Measured by Vaccinia-specific ELISA
GMT based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.
Time frame: within 12 weeks
Population: Per-protocol Set for Immunogenicity
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 | GMTs as Measured by Vaccinia-specific ELISA | Week 2 | 104.9 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific ELISA | Week 6 | 1076.9 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific ELISA | Week 1 | 1.6 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific ELISA | Week 8 | 671.9 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific ELISA | Week 4 | 129.8 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific ELISA | Week 12 | 550.5 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific ELISA | Week 0 | 1.2 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific ELISA | Week 12 | NA Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific ELISA | Week 0 | 1.2 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific ELISA | Week 1 | 1.2 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific ELISA | Week 2 | 21.9 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific ELISA | Week 4 | 194.6 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific ELISA | Week 6 | 149.2 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific ELISA | Week 8 | 113.7 Titer |
Secondary
GMTs as Measured by Vaccinia-specific PRNT
GMT based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.
Time frame: within 12 weeks
Population: Per-protocol Set for Immunogenicity
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 | GMTs as Measured by Vaccinia-specific PRNT | Week 2 | 16.2 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific PRNT | Week 6 | 153.5 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific PRNT | Week 1 | 1.1 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific PRNT | Week 8 | 118.2 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific PRNT | Week 4 | 16.9 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific PRNT | Week 12 | 96.5 Titer |
| Group 1 | GMTs as Measured by Vaccinia-specific PRNT | Week 0 | 1.0 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific PRNT | Week 12 | NA Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific PRNT | Week 0 | 1.0 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific PRNT | Week 1 | 1.0 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific PRNT | Week 2 | 16.2 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific PRNT | Week 4 | 79.3 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific PRNT | Week 6 | 64.7 Titer |
| Group 2 | GMTs as Measured by Vaccinia-specific PRNT | Week 8 | 67.1 Titer |
Secondary
GMTs at the Individual Peak Measured by Vaccinia-specific PRNT
Individual Peak was the maximum titer per subject from Visit 1 to Visit 7 (Week 8) in Group 1 and maximum titer from Visit 1 to Visit 6 (Week 8) in Group 2. Titers below the detection limit are included with a value of 1.
Time frame: within 8 weeks (for both groups)
Population: Per-protocol Set for Immunogenicity
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 | GMTs at the Individual Peak Measured by Vaccinia-specific PRNT | 201.5 Titer |
| Group 2 | GMTs at the Individual Peak Measured by Vaccinia-specific PRNT | 117.8 Titer |
Secondary
GMTs at the Peak Visits and Individual Peak Measured by Vaccinia-specific ELISA
Peak Visit was defined as Day 42 for Group 1 and Day 28 for Group 2. Individual Peak was the maximum titer per subject from Visit 1 to Visit 7 (Week 8) in Group 1 and maximum titer from Visit 1 to Visit 6 (Week 8) in Group 2. Titers below the detection limit are included with a value of 1.
Time frame: within 8 weeks (for both groups)
Population: Per-protocol Set for Immunogenicity
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 | GMTs at the Peak Visits and Individual Peak Measured by Vaccinia-specific ELISA | Peak Visit | 1076.9 Titer |
| Group 1 | GMTs at the Peak Visits and Individual Peak Measured by Vaccinia-specific ELISA | Individual Peak | 1105.2 Titer |
| Group 2 | GMTs at the Peak Visits and Individual Peak Measured by Vaccinia-specific ELISA | Peak Visit | 194.6 Titer |
| Group 2 | GMTs at the Peak Visits and Individual Peak Measured by Vaccinia-specific ELISA | Individual Peak | 214.0 Titer |
Secondary
Incidence of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis, i.e. Adverse Events of Special Interest (AESIs)
In this clinical trial, an AESI was defined as any cardiac sign or symptom developed since the first vaccination, any ECG changes determined to be clinically significant, or any cardiac enzyme results of Troponin I ≥ 2 x ULN.
Time frame: Within 38 weeks for Group 1 and 30 weeks for Group 2
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Incidence of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis, i.e. Adverse Events of Special Interest (AESIs) | 2 Participants |
| Group 2 | Incidence of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis, i.e. Adverse Events of Special Interest (AESIs) | 2 Participants |
| Group 1, Period 3 | Incidence of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis, i.e. Adverse Events of Special Interest (AESIs) | 3 Participants |
| Group 2 | Incidence of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis, i.e. Adverse Events of Special Interest (AESIs) | 4 Participants |
Secondary
Incidence of Lymphadenopathy
Incidence of events of Lymphadenopathy. Pooled solicited and unsolicited events.
Time frame: within 29 days after vaccination
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Incidence of Lymphadenopathy | 24 Participants |
| Group 2 | Incidence of Lymphadenopathy | 15 Participants |
| Group 1, Period 3 | Incidence of Lymphadenopathy | 17 Participants |
| Group 2 | Incidence of Lymphadenopathy | 109 Participants |
Secondary
Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC)
Take was assessed as either full, partial, or absent take by the ITRC based on Day 6-8 evaluations following ACAM2000 vaccination using subject profiles that contained supportive data up to Day 14 following ACAM2000 vaccination (in accordance with the ITRC Charter).
Time frame: Day 6-8 visit following ACAM2000 vaccination
Population: Per-protocol Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC) | Full Take | 23.0 percentage of subjects |
| Group 1 | Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC) | Partial Take | 23.0 percentage of subjects |
| Group 1 | Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC) | Absent Take | 53.9 percentage of subjects |
| Group 1 | Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC) | Missing | 0 percentage of subjects |
| Group 2 | Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC) | Missing | 1.2 percentage of subjects |
| Group 2 | Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC) | Full Take | 92.5 percentage of subjects |
| Group 2 | Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC) | Absent Take | 1.9 percentage of subjects |
| Group 2 | Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC) | Partial Take | 4.3 percentage of subjects |
Secondary
Intensity of Any Non-serious AEs
Presentation of non-serious AEs by intensity
Time frame: within 29 days after vaccination
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Intensity of Any Non-serious AEs | Mild | 233 Events |
| Group 1 | Intensity of Any Non-serious AEs | Severe | 4 Events |
| Group 1 | Intensity of Any Non-serious AEs | Moderate | 20 Events |
| Group 2 | Intensity of Any Non-serious AEs | Mild | 141 Events |
| Group 2 | Intensity of Any Non-serious AEs | Severe | 1 Events |
| Group 2 | Intensity of Any Non-serious AEs | Moderate | 16 Events |
| Group 1, Period 3 | Intensity of Any Non-serious AEs | Moderate | 18 Events |
| Group 1, Period 3 | Intensity of Any Non-serious AEs | Mild | 143 Events |
| Group 1, Period 3 | Intensity of Any Non-serious AEs | Severe | 5 Events |
| Group 2 | Intensity of Any Non-serious AEs | Mild | 163 Events |
| Group 2 | Intensity of Any Non-serious AEs | Severe | 7 Events |
| Group 2 | Intensity of Any Non-serious AEs | Moderate | 25 Events |
Secondary
Intensity of Any Serious Adverse Event (SAE)
Presentation of SAEs by intensity
Time frame: Within 38 weeks for Group 1 and 30 weeks for Group 2
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Intensity of Any Serious Adverse Event (SAE) | Mild: routine daily activity not impaired | 0 participants |
| Group 1 | Intensity of Any Serious Adverse Event (SAE) | Moderate: routine daily activity impaired | 0 participants |
| Group 1 | Intensity of Any Serious Adverse Event (SAE) | Severe: prevents routine daily activities | 1 participants |
| Group 1 | Intensity of Any Serious Adverse Event (SAE) | Life threatening | 4 participants |
| Group 2 | Intensity of Any Serious Adverse Event (SAE) | Life threatening | 2 participants |
| Group 2 | Intensity of Any Serious Adverse Event (SAE) | Mild: routine daily activity not impaired | 0 participants |
| Group 2 | Intensity of Any Serious Adverse Event (SAE) | Severe: prevents routine daily activities | 1 participants |
| Group 2 | Intensity of Any Serious Adverse Event (SAE) | Moderate: routine daily activity impaired | 0 participants |
Secondary
Investigator-measured Lesion Diameter in mm at Day 13-15 After Scarification With ACAM2000
The lesion diameter at Day 13-15 was defined as the major lesion diameter measured on Day 13-15 (after scarification)
Time frame: Day 13-15 after ACAM2000 scarification
Population: Per-protocol Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Investigator-measured Lesion Diameter in mm at Day 13-15 After Scarification With ACAM2000 | 0.0 mm |
| Group 2 | Investigator-measured Lesion Diameter in mm at Day 13-15 After Scarification With ACAM2000 | 10.0 mm |
Secondary
Investigator-measured Lesion Diameter in mm at Day 6-8 After Scarification With ACAM2000
The lesion diameter at Day 6-8 was defined as the major lesion diameter measured on Day 6-8 (after scarification)
Time frame: Day 6-8 after ACAM2000 scarification
Population: Per-protocol Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Investigator-measured Lesion Diameter in mm at Day 6-8 After Scarification With ACAM2000 | 0.0 mm |
| Group 2 | Investigator-measured Lesion Diameter in mm at Day 6-8 After Scarification With ACAM2000 | 8.0 mm |
Secondary
Investigator-measured Maximum Lesion Diameter (MLD) in mm After Scarification With ACAM2000
The MLD was defined as the largest major diameter measured across the lesion on Day 6-8 (after scarification) or Day 13-15 (after scarification)
Time frame: Day 6-8 and Day 13-15 after ACAM2000 scarification
Population: Per-protocol Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Investigator-measured Maximum Lesion Diameter (MLD) in mm After Scarification With ACAM2000 | 0.0 mm |
| Group 2 | Investigator-measured Maximum Lesion Diameter (MLD) in mm After Scarification With ACAM2000 | 11.0 mm |
Secondary
Lesion Area in mm2 at Day 13-15 After Scarification With ACAM2000
Lesion area was measured by the Investigator using the SilhouetteConnect camera system and confirmed by the blinded ITRC.
Time frame: Day 13-15 after ACAM2000 scarification
Population: Per-protocol Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Lesion Area in mm2 at Day 13-15 After Scarification With ACAM2000 | 0.0 mm2 |
| Group 2 | Lesion Area in mm2 at Day 13-15 After Scarification With ACAM2000 | 75.0 mm2 |
Secondary
Lesion Area in mm2 at Day 6-8 After Scarification With ACAM2000
Lesion area was measured by the Investigator using the SilhouetteConnect camera system and confirmed by the blinded ITRC.
Time frame: Day 6-8 after ACAM2000 scarification
Population: Per-protocol Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Lesion Area in mm2 at Day 6-8 After Scarification With ACAM2000 | 0.0 mm2 |
| Group 2 | Lesion Area in mm2 at Day 6-8 After Scarification With ACAM2000 | 37.0 mm2 |
Secondary
Major Lesion Size, Major Erythema, and Major Induration Diameter
Daily measurement of major lesion size, major erythema, and major induration diameter (mm) based on physical appearance of vaccination site as documented in the memory aid. If the shape of the lesion, erythema \[excludes lymphangitis\], and induration observed was not round but rather asymmetrical, then the largest \[or major\] cross-sectional measurement was recorded.
Time frame: Within 15 days after scarification with ACAM2000
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1 | Major Lesion Size, Major Erythema, and Major Induration Diameter | Maximum Lesion Diameter | 5.0 mm |
| Group 1 | Major Lesion Size, Major Erythema, and Major Induration Diameter | Maximum Erythema | 6.0 mm |
| Group 1 | Major Lesion Size, Major Erythema, and Major Induration Diameter | Maximum Induration | 5.0 mm |
| Group 2 | Major Lesion Size, Major Erythema, and Major Induration Diameter | Maximum Lesion Diameter | 11.5 mm |
| Group 2 | Major Lesion Size, Major Erythema, and Major Induration Diameter | Maximum Erythema | 26.0 mm |
| Group 2 | Major Lesion Size, Major Erythema, and Major Induration Diameter | Maximum Induration | 15.0 mm |
Secondary
PRNT Seroconversion Rates at Peak Visits
Seroconversion rate based on PRNT. Seroconversion is defined as the appearance of antibody titers greater than or equal 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: Group 1 at Week 6; Group 2 at Week 4
Population: Per-protocol Set for Immunogenicity
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | PRNT Seroconversion Rates at Peak Visits | 100.0 percentage of subjects |
| Group 2 | PRNT Seroconversion Rates at Peak Visits | 97.3 percentage of subjects |
Secondary
Related Grade >=3 Adverse Events
Incidence of any Grade 3 or 4 adverse events (AEs) possibly, probably, or definitely related to the vaccine. Pooled solicited (general only) and unsolicited AEs.
Time frame: within 29 days after vaccination
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Related Grade >=3 Adverse Events | 3 Participants |
| Group 2 | Related Grade >=3 Adverse Events | 2 Participants |
| Group 1, Period 3 | Related Grade >=3 Adverse Events | 3 Participants |
| Group 2 | Related Grade >=3 Adverse Events | 22 Participants |
Secondary
Relationship to Vaccine of Any Non-serious AEs
Presentation of non-serious AEs by relationship to study vaccine
Time frame: within 29 days after vaccination
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Relationship to Vaccine of Any Non-serious AEs | Probable | 5 Events |
| Group 1 | Relationship to Vaccine of Any Non-serious AEs | Definite | 107 Events |
| Group 1 | Relationship to Vaccine of Any Non-serious AEs | Unlikely | 24 Events |
| Group 1 | Relationship to Vaccine of Any Non-serious AEs | Unrelated/None | 94 Events |
| Group 1 | Relationship to Vaccine of Any Non-serious AEs | Possible | 27 Events |
| Group 2 | Relationship to Vaccine of Any Non-serious AEs | Unrelated/None | 67 Events |
| Group 2 | Relationship to Vaccine of Any Non-serious AEs | Probable | 1 Events |
| Group 2 | Relationship to Vaccine of Any Non-serious AEs | Definite | 56 Events |
| Group 2 | Relationship to Vaccine of Any Non-serious AEs | Unlikely | 19 Events |
| Group 2 | Relationship to Vaccine of Any Non-serious AEs | Possible | 15 Events |
| Group 1, Period 3 | Relationship to Vaccine of Any Non-serious AEs | Unrelated/None | 110 Events |
| Group 1, Period 3 | Relationship to Vaccine of Any Non-serious AEs | Possible | 18 Events |
| Group 1, Period 3 | Relationship to Vaccine of Any Non-serious AEs | Unlikely | 29 Events |
| Group 1, Period 3 | Relationship to Vaccine of Any Non-serious AEs | Probable | 0 Events |
| Group 1, Period 3 | Relationship to Vaccine of Any Non-serious AEs | Definite | 9 Events |
| Group 2 | Relationship to Vaccine of Any Non-serious AEs | Probable | 6 Events |
| Group 2 | Relationship to Vaccine of Any Non-serious AEs | Unlikely | 23 Events |
| Group 2 | Relationship to Vaccine of Any Non-serious AEs | Possible | 30 Events |
| Group 2 | Relationship to Vaccine of Any Non-serious AEs | Unrelated/None | 102 Events |
| Group 2 | Relationship to Vaccine of Any Non-serious AEs | Definite | 34 Events |
Secondary
Relationship to Vaccine of Any Serious Adverse Event (SAE)
Presentation of SAEs by relationship to study vaccine
Time frame: Within 38 weeks for Group 1 and 30 weeks for Group 2
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Relationship to Vaccine of Any Serious Adverse Event (SAE) | Definite | 0 Events |
| Group 1 | Relationship to Vaccine of Any Serious Adverse Event (SAE) | Unlikely | 1 Events |
| Group 1 | Relationship to Vaccine of Any Serious Adverse Event (SAE) | Possible | 0 Events |
| Group 1 | Relationship to Vaccine of Any Serious Adverse Event (SAE) | Probable | 0 Events |
| Group 1 | Relationship to Vaccine of Any Serious Adverse Event (SAE) | Unrelated/None | 4 Events |
| Group 2 | Relationship to Vaccine of Any Serious Adverse Event (SAE) | Probable | 0 Events |
| Group 2 | Relationship to Vaccine of Any Serious Adverse Event (SAE) | Definite | 0 Events |
| Group 2 | Relationship to Vaccine of Any Serious Adverse Event (SAE) | Unrelated/None | 2 Events |
| Group 2 | Relationship to Vaccine of Any Serious Adverse Event (SAE) | Possible | 0 Events |
| Group 2 | Relationship to Vaccine of Any Serious Adverse Event (SAE) | Unlikely | 1 Events |
Secondary
Solicited General AEs
Occurrence, intensity and relationship of solicited general AEs (body temperature \[fever\], headache, myalgia \[muscle pain\], chills, nausea, fatigue, malaise)
Time frame: within 15 days after vaccination
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Solicited General AEs | Nausea, Grade 2, Related | 0 Participants |
| Group 1 | Solicited General AEs | Malaise, Grade 2, Related | 5 Participants |
| Group 1 | Solicited General AEs | Chills, Grade 2, Related | 0 Participants |
| Group 1 | Solicited General AEs | Nausea, Grade 1, Related | 7 Participants |
| Group 1 | Solicited General AEs | Fatigue, Grade 3, Related | 1 Participants |
| Group 1 | Solicited General AEs | Chills, Grade 3, Related | 1 Participants |
| Group 1 | Solicited General AEs | Malaise, Grade 3, Related | 2 Participants |
| Group 1 | Solicited General AEs | Pyrexia, Grade 3, Related | 0 Participants |
| Group 1 | Solicited General AEs | Nausea, Grade 3, Related | 1 Participants |
| Group 1 | Solicited General AEs | Fatigue, Grade 1, Related | 29 Participants |
| Group 1 | Solicited General AEs | Pyrexia, Grade 1, Related | 0 Participants |
| Group 1 | Solicited General AEs | Headache, Grade 2, Related | 6 Participants |
| Group 1 | Solicited General AEs | Headache, Grade 3, Related | 1 Participants |
| Group 1 | Solicited General AEs | Headache, Grade 1, Related | 25 Participants |
| Group 1 | Solicited General AEs | Malaise, Grade 1, Related | 16 Participants |
| Group 1 | Solicited General AEs | Myalgia, Grade 1, Related | 28 Participants |
| Group 1 | Solicited General AEs | Myalgia, Grade 2, Related | 5 Participants |
| Group 1 | Solicited General AEs | Fatigue, Grade 2, Related | 7 Participants |
| Group 1 | Solicited General AEs | Pyrexia, Grade 2, Related | 2 Participants |
| Group 1 | Solicited General AEs | Myalgia, Grade 3, Related | 0 Participants |
| Group 1 | Solicited General AEs | Chills, Grade 1, Related | 1 Participants |
| Group 2 | Solicited General AEs | Nausea, Grade 1, Related | 4 Participants |
| Group 2 | Solicited General AEs | Headache, Grade 2, Related | 3 Participants |
| Group 2 | Solicited General AEs | Malaise, Grade 2, Related | 2 Participants |
| Group 2 | Solicited General AEs | Fatigue, Grade 2, Related | 2 Participants |
| Group 2 | Solicited General AEs | Chills, Grade 2, Related | 2 Participants |
| Group 2 | Solicited General AEs | Pyrexia, Grade 1, Related | 0 Participants |
| Group 2 | Solicited General AEs | Pyrexia, Grade 2, Related | 0 Participants |
| Group 2 | Solicited General AEs | Headache, Grade 3, Related | 2 Participants |
| Group 2 | Solicited General AEs | Chills, Grade 3, Related | 0 Participants |
| Group 2 | Solicited General AEs | Myalgia, Grade 2, Related | 5 Participants |
| Group 2 | Solicited General AEs | Chills, Grade 1, Related | 0 Participants |
| Group 2 | Solicited General AEs | Nausea, Grade 2, Related | 2 Participants |
| Group 2 | Solicited General AEs | Malaise, Grade 3, Related | 1 Participants |
| Group 2 | Solicited General AEs | Myalgia, Grade 3, Related | 1 Participants |
| Group 2 | Solicited General AEs | Headache, Grade 1, Related | 11 Participants |
| Group 2 | Solicited General AEs | Nausea, Grade 3, Related | 0 Participants |
| Group 2 | Solicited General AEs | Fatigue, Grade 3, Related | 1 Participants |
| Group 2 | Solicited General AEs | Pyrexia, Grade 3, Related | 1 Participants |
| Group 2 | Solicited General AEs | Myalgia, Grade 1, Related | 13 Participants |
| Group 2 | Solicited General AEs | Fatigue, Grade 1, Related | 14 Participants |
| Group 2 | Solicited General AEs | Malaise, Grade 1, Related | 6 Participants |
| Group 1, Period 3 | Solicited General AEs | Fatigue, Grade 1, Related | 21 Participants |
| Group 1, Period 3 | Solicited General AEs | Fatigue, Grade 2, Related | 7 Participants |
| Group 1, Period 3 | Solicited General AEs | Fatigue, Grade 3, Related | 1 Participants |
| Group 1, Period 3 | Solicited General AEs | Malaise, Grade 1, Related | 12 Participants |
| Group 1, Period 3 | Solicited General AEs | Malaise, Grade 2, Related | 8 Participants |
| Group 1, Period 3 | Solicited General AEs | Headache, Grade 1, Related | 17 Participants |
| Group 1, Period 3 | Solicited General AEs | Malaise, Grade 3, Related | 2 Participants |
| Group 1, Period 3 | Solicited General AEs | Headache, Grade 2, Related | 7 Participants |
| Group 1, Period 3 | Solicited General AEs | Headache, Grade 3, Related | 1 Participants |
| Group 1, Period 3 | Solicited General AEs | Pyrexia, Grade 1, Related | 0 Participants |
| Group 1, Period 3 | Solicited General AEs | Myalgia, Grade 1, Related | 15 Participants |
| Group 1, Period 3 | Solicited General AEs | Myalgia, Grade 2, Related | 2 Participants |
| Group 1, Period 3 | Solicited General AEs | Myalgia, Grade 3, Related | 0 Participants |
| Group 1, Period 3 | Solicited General AEs | Chills, Grade 1, Related | 8 Participants |
| Group 1, Period 3 | Solicited General AEs | Pyrexia, Grade 2, Related | 1 Participants |
| Group 1, Period 3 | Solicited General AEs | Chills, Grade 2, Related | 2 Participants |
| Group 1, Period 3 | Solicited General AEs | Nausea, Grade 1, Related | 6 Participants |
| Group 1, Period 3 | Solicited General AEs | Chills, Grade 3, Related | 0 Participants |
| Group 1, Period 3 | Solicited General AEs | Nausea, Grade 2, Related | 4 Participants |
| Group 1, Period 3 | Solicited General AEs | Nausea, Grade 3, Related | 1 Participants |
| Group 1, Period 3 | Solicited General AEs | Pyrexia, Grade 3, Related | 0 Participants |
| Group 2 | Solicited General AEs | Malaise, Grade 3, Related | 10 Participants |
| Group 2 | Solicited General AEs | Nausea, Grade 1, Related | 21 Participants |
| Group 2 | Solicited General AEs | Pyrexia, Grade 1, Related | 1 Participants |
| Group 2 | Solicited General AEs | Pyrexia, Grade 2, Related | 1 Participants |
| Group 2 | Solicited General AEs | Pyrexia, Grade 3, Related | 1 Participants |
| Group 2 | Solicited General AEs | Headache, Grade 1, Related | 38 Participants |
| Group 2 | Solicited General AEs | Headache, Grade 2, Related | 21 Participants |
| Group 2 | Solicited General AEs | Headache, Grade 3, Related | 9 Participants |
| Group 2 | Solicited General AEs | Myalgia, Grade 1, Related | 44 Participants |
| Group 2 | Solicited General AEs | Myalgia, Grade 2, Related | 21 Participants |
| Group 2 | Solicited General AEs | Myalgia, Grade 3, Related | 7 Participants |
| Group 2 | Solicited General AEs | Chills, Grade 1, Related | 19 Participants |
| Group 2 | Solicited General AEs | Chills, Grade 2, Related | 12 Participants |
| Group 2 | Solicited General AEs | Nausea, Grade 2, Related | 12 Participants |
| Group 2 | Solicited General AEs | Nausea, Grade 3, Related | 6 Participants |
| Group 2 | Solicited General AEs | Fatigue, Grade 1, Related | 45 Participants |
| Group 2 | Solicited General AEs | Fatigue, Grade 2, Related | 30 Participants |
| Group 2 | Solicited General AEs | Fatigue, Grade 3, Related | 8 Participants |
| Group 2 | Solicited General AEs | Malaise, Grade 1, Related | 30 Participants |
| Group 2 | Solicited General AEs | Malaise, Grade 2, Related | 25 Participants |
| Group 2 | Solicited General AEs | Chills, Grade 3, Related | 2 Participants |
Secondary
Solicited Local AEs: Intensity
Incidence of solicited local AEs (pain, redness \[erythema\], swelling, induration, itching \[pruritus\])
Time frame: within 15 days after vaccination
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 1 | 44 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 2 | 3 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 3 | 0 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 1 | 14 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 2 | 9 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 1 | 24 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 3 | 0 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 2 | 21 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 1 | 72 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 2 | 5 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 3 | 0 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 3 | 4 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 3 | 2 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 2 | 1 Participants |
| Group 1 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 1 | 23 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 3 | 0 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 2 | 6 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 1 | 49 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 2 | 22 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 3 | 0 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 1 | 40 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 2 | 10 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 3 | 0 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 1 | 16 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 3 | 0 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 1 | 11 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 2 | 2 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 1 | 19 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 2 | 1 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 3 | 0 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 1 | 46 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 1 | 106 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 2 | 11 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 3 | 0 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 1 | 44 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 3 | 1 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 2 | 0 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 2 | 1 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 2 | 6 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 3 | 0 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 1 | 99 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 2 | 9 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 1 | 21 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 3 | 0 Participants |
| Group 1, Period 3 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 3 | 1 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 3 | 5 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 2 | 17 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 1 | 105 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 3 | 0 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 1 | 58 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 3 | 1 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 3 | 33 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 2 | 60 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 3 | 18 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 1 | 125 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Swelling, Grade 1 | 120 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pruritus, Grade 1 | 101 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Erythema, Grade 2 | 81 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Induration, Grade 2 | 7 Participants |
| Group 2 | Solicited Local AEs: Intensity | Injection Site Pain, Grade 2 | 44 Participants |