Smallpox
Conditions
Brief summary
A randomized, double-blind, placebo-controlled Phase III trial to evaluate immunogenicity and safety of three consecutive production lots of IMVAMUNE® (MVA-BN®) smallpox vaccine in healthy, vaccinia-naïve subjects.
Interventions
BIOLOGICALIMVAMUNE®
0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose)
OTHERPlacebo
0.5 ml TBS
Sponsors
Bavarian Nordic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female subjects, 18 to 40 years of age * The subject has read, signed and dated the informed consent form, 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 procedures * BMI ≥ 18.5 and \< 35 * 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 or with a history of hysterectomy (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products) * WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to each vaccination * White blood cells ≥ 2,500/mm3 \< ULN * Absolute neutrophil count (ANC) within normal limits * Hemoglobin within normal limits * Platelets within normal limits * Adequate renal function defined as a calculated Creatinine Clearance (CrCl) \> 60 ml/min as estimated by the Cockcroft-Gault equation: * For men: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dl x 72) = CrCl (ml/min) * For women: multiply the result by 0.85 = CrCl (ml/min). * Adequate hepatic function defined as: * a. Total bilirubin ≤ 1.5 x ULN in the absence of other evidence of significant liver disease * b. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 1.5 x ULN * Troponin I \< 2 x ULN * 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 in a row, ST elevation consistent with ischemia)
Exclusion criteria
* Typical vaccinia scar * Known or suspected history of smallpox vaccination * History of vaccination with any poxvirus-based vaccine * US Military service prior to 1991 or after January 2003 * 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 or would limit the subject's ability to complete the trial * 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, HIV Infection, clinically significant liver disease (including chronic active HBV or HCV), 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 tumor site * History or clinical manifestation of clinically significant and severe hematological, pulmonary, central nervous, cardiovascular or gastrointestinal disorders * Clinically significant mental disorder not adequately controlled by medical treatment * 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 * Known history of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before age 50 years * 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 * Active or history of chronic alcohol abuse and/or intravenous and/or nasal drug abuse (within the past 6 months) * Known allergy to IMVAMUNE® vaccine and its constituents, e.g. tris (hydroxymethyl)-amino methane, including know allergy to egg or aminoglycosides * History of anaphylaxis or severe allergic reaction to any vaccine * Acute disease (illness with or without a fever) at the time enrollment * Body temperature ≥100.4°F (≥38.0°C) at the time of enrollment * Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior to or after trial vaccination * Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior to or after trial vaccination * Chronic systemic administration (defined as more than 14 days) of \> 5 mg prednisone (or equivalent)/day or any other immune-modifying drugs during a period starting from three months prior to administration of the vaccine and ending at last physical trial visit (V5) * 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 three months prior to administration of the vaccine and ending at last physical trial visit (V5) * 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 * Trial personnel
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PRNT GMT | 2 weeks following the second vaccination | Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Titers below the detection limit are included with a value of '1'. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PRNT Seroconversion Rate | 2 weeks following the second vaccination | Seroconversion rate based on Plaque Reduction Neutralization Test (PRNT). Seroconversion 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. |
| ELISA Seroconversion Rate | 2 weeks following the second vaccination | Seroconversion rate based on Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion 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. |
| Correlation PRNT vs ELISA Titers | 2 weeks following the second vaccination | Pearson Correlation Coefficient between the log10 transformed PRNT titers and the log10 transformed ELISA titers |
| Serious Adverse Events | within 30 weeks | Incidence, relationship and intensity of any Serious Adverse Event (SAE) |
| Cardiac Signs or Symptoms | within 30 weeks | Incidence, relationship and intensity of any cardiac sign or symptom indicating a case of myo-/pericarditis (Adverse Event of Special Interest (AESI)). An AESI was defined in this trial as: * Any cardiac sign or symptom developed since the first vaccination * ECG changes determined to be clinically significant * Cardiac enzyme Troponin I \>= 2 x ULN (\>= Grade 2) |
| ELISA GMT | 2 weeks following the second vaccination | Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Titers below the detection limit are included with a value of '1'. |
| Unsolicited Non-serious AEs: Intensity | within 29 days after any vaccination | Occurrence of unsolicited non-serious AEs by Intensity |
| Unsolicited Non-serious AEs: Relationship to Vaccination | within 29 days after any vaccination | Occurrence of unsolicited non-serious AEs by relationship to study vaccine |
| Solicited Local AEs | within 8 days after any vaccination | Incidence and intensity of solicited local AEs (redness, swelling, induration, pruritus and pain). Percentages based on subjects with at least one completed diary card. |
| Solicited General AEs | within 8 days after any vaccination | Incidence of solicited general AEs (pyrexia, headache, myalgia, chills, nausea, and fatigue): Intensity and relationship to vaccination. Percentages based on subjects with at least one completed diary card. |
| Related Grade >=3 Adverse Events | within 29 days after any vaccination | Incidence of any Grade \>=3 Adverse Events probably, possibly or definitely related to the trial vaccine. Pooled solicited (general only) and unsolicited AEs |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #1
IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose) | 999 |
| Group 2 Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #2
IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose) | 1,005 |
| Group 3 Two vaccinations four weeks apart (at Day 0 and Day 28) with IMVAMUNE® Lot #3
IMVAMUNE®: 0.5 ml IMVAMUNE® vaccine containing at least 1 x 10E8 TCID50 (standard dose) | 999 |
| Group 4 Two vaccinations four weeks apart (at Day 0 and Day 28) with 0.5 ml Placebo, Tris-buffered saline (TBS)
Placebo: 0.5 ml TBS | 1,002 |
| Total | 4,005 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Group 4 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 27.6 years STANDARD_DEVIATION 6.28 | 27.5 years STANDARD_DEVIATION 6.24 | 28.0 years STANDARD_DEVIATION 6.31 | 27.7 years STANDARD_DEVIATION 6.38 | 27.7 years STANDARD_DEVIATION 6.3 |
| Sex: Female, Male Female | 526 Participants | 527 Participants | 494 Participants | 539 Participants | 2086 Participants |
| Sex: Female, Male Male | 473 Participants | 478 Participants | 505 Participants | 463 Participants | 1919 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 | 1 / 999 | 0 / 1,005 | 0 / 999 | 0 / 1,002 |
| other Total, other adverse events | 53 / 999 | 70 / 1,005 | 65 / 999 | 48 / 1,002 |
| serious Total, serious adverse events | 11 / 999 | 7 / 1,005 | 7 / 999 | 8 / 1,002 |
Outcome results
Primary
PRNT GMT
Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Titers below the detection limit are included with a value of '1'.
Time frame: 2 weeks following the second vaccination
Population: Per-protocol Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 | PRNT GMT | 110.7 Titer |
| Group 2 | PRNT GMT | 100.5 Titer |
| Group 3 | PRNT GMT | 117.2 Titer |
| Group 4 | PRNT GMT | 1.0 Titer |
95% CI: [0.9992, 1.2136]
95% CI: [0.8554, 1.0427]
95% CI: [0.7753, 0.9488]
Secondary
Cardiac Signs or Symptoms
Incidence, relationship and intensity of any cardiac sign or symptom indicating a case of myo-/pericarditis (Adverse Event of Special Interest (AESI)). An AESI was defined in this trial as: * Any cardiac sign or symptom developed since the first vaccination * ECG changes determined to be clinically significant * Cardiac enzyme Troponin I \>= 2 x ULN (\>= Grade 2)
Time frame: within 30 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Cardiac Signs or Symptoms | Any AESI | 2 Participants |
| Group 1 | Cardiac Signs or Symptoms | Any AESI assessed as related to vaccine | 0 Participants |
| Group 1 | Cardiac Signs or Symptoms | Any AESI with intensity >= Grade 3 | 0 Participants |
| Group 2 | Cardiac Signs or Symptoms | Any AESI | 5 Participants |
| Group 2 | Cardiac Signs or Symptoms | Any AESI assessed as related to vaccine | 1 Participants |
| Group 2 | Cardiac Signs or Symptoms | Any AESI with intensity >= Grade 3 | 0 Participants |
| Group 3 | Cardiac Signs or Symptoms | Any AESI with intensity >= Grade 3 | 0 Participants |
| Group 3 | Cardiac Signs or Symptoms | Any AESI | 1 Participants |
| Group 3 | Cardiac Signs or Symptoms | Any AESI assessed as related to vaccine | 1 Participants |
| Group 4 | Cardiac Signs or Symptoms | Any AESI | 1 Participants |
| Group 4 | Cardiac Signs or Symptoms | Any AESI assessed as related to vaccine | 0 Participants |
| Group 4 | Cardiac Signs or Symptoms | Any AESI with intensity >= Grade 3 | 0 Participants |
Secondary
Correlation PRNT vs ELISA Titers
Pearson Correlation Coefficient between the log10 transformed PRNT titers and the log10 transformed ELISA titers
Time frame: 2 weeks following the second vaccination
Population: Per-protocol Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Correlation PRNT vs ELISA Titers | 0.581 Pearson correlation coefficient |
| Group 2 | Correlation PRNT vs ELISA Titers | 0.620 Pearson correlation coefficient |
| Group 3 | Correlation PRNT vs ELISA Titers | 0.612 Pearson correlation coefficient |
| Group 4 | Correlation PRNT vs ELISA Titers | 0.486 Pearson correlation coefficient |
Secondary
ELISA GMT
Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Titers below the detection limit are included with a value of '1'.
Time frame: 2 weeks following the second vaccination
Population: Per-protocol Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 | ELISA GMT | 901.0 Titer |
| Group 2 | ELISA GMT | 794.4 Titer |
| Group 3 | ELISA GMT | 946.7 Titer |
| Group 4 | ELISA GMT | 1.2 Titer |
Secondary
ELISA Seroconversion Rate
Seroconversion rate based on Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion 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: 2 weeks following the second vaccination
Population: Per-protocol Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | ELISA Seroconversion Rate | 99.7 percentage of subjects |
| Group 2 | ELISA Seroconversion Rate | 99.5 percentage of subjects |
| Group 3 | ELISA Seroconversion Rate | 100.0 percentage of subjects |
| Group 4 | ELISA Seroconversion Rate | 2.0 percentage of subjects |
Secondary
PRNT Seroconversion Rate
Seroconversion rate based on Plaque Reduction Neutralization Test (PRNT). Seroconversion 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: 2 weeks following the second vaccination
Population: Per-protocol Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | PRNT Seroconversion Rate | 99.8 percentage of subjects |
| Group 2 | PRNT Seroconversion Rate | 99.7 percentage of subjects |
| Group 3 | PRNT Seroconversion Rate | 99.8 percentage of subjects |
| Group 4 | PRNT Seroconversion Rate | 1.4 percentage of subjects |
Secondary
Related Grade >=3 Adverse Events
Incidence of any Grade \>=3 Adverse Events probably, possibly or definitely related to the trial vaccine. Pooled solicited (general only) and unsolicited AEs
Time frame: within 29 days after any vaccination
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Related Grade >=3 Adverse Events | 58 Participants |
| Group 2 | Related Grade >=3 Adverse Events | 57 Participants |
| Group 3 | Related Grade >=3 Adverse Events | 53 Participants |
| Group 4 | Related Grade >=3 Adverse Events | 27 Participants |
Secondary
Serious Adverse Events
Incidence, relationship and intensity of any Serious Adverse Event (SAE)
Time frame: within 30 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Serious Adverse Events | Any SAE assessed as related to vaccine | 0 Participants |
| Group 1 | Serious Adverse Events | Any SAE | 11 Participants |
| Group 1 | Serious Adverse Events | Any SAE with intensity >= Grade 3 | 8 Participants |
| Group 2 | Serious Adverse Events | Any SAE with intensity >= Grade 3 | 6 Participants |
| Group 2 | Serious Adverse Events | Any SAE | 7 Participants |
| Group 2 | Serious Adverse Events | Any SAE assessed as related to vaccine | 0 Participants |
| Group 3 | Serious Adverse Events | Any SAE assessed as related to vaccine | 0 Participants |
| Group 3 | Serious Adverse Events | Any SAE | 7 Participants |
| Group 3 | Serious Adverse Events | Any SAE with intensity >= Grade 3 | 6 Participants |
| Group 4 | Serious Adverse Events | Any SAE with intensity >= Grade 3 | 5 Participants |
| Group 4 | Serious Adverse Events | Any SAE | 8 Participants |
| Group 4 | Serious Adverse Events | Any SAE assessed as related to vaccine | 1 Participants |
Secondary
Solicited General AEs
Incidence of solicited general AEs (pyrexia, headache, myalgia, chills, nausea, and fatigue): Intensity and relationship to vaccination. Percentages based on subjects with at least one completed diary card.
Time frame: within 8 days after any vaccination
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Solicited General AEs | Chills: Grade >=3 | 10 Participants |
| Group 1 | Solicited General AEs | Pyrexia: Related | 13 Participants |
| Group 1 | Solicited General AEs | Nausea: Grade >=3 | 13 Participants |
| Group 1 | Solicited General AEs | Headache: Grade >=3 | 28 Participants |
| Group 1 | Solicited General AEs | Chills: Related | 96 Participants |
| Group 1 | Solicited General AEs | Chills: Any | 108 Participants |
| Group 1 | Solicited General AEs | Nausea: Any | 166 Participants |
| Group 1 | Solicited General AEs | Myalgia: Any | 425 Participants |
| Group 1 | Solicited General AEs | Headache: Any | 321 Participants |
| Group 1 | Solicited General AEs | Pyrexia: Any | 17 Participants |
| Group 1 | Solicited General AEs | Fatigue: Any | 305 Participants |
| Group 1 | Solicited General AEs | Myalgia: Related | 404 Participants |
| Group 1 | Solicited General AEs | Nausea: Related | 146 Participants |
| Group 1 | Solicited General AEs | Fatigue: Grade >=3 | 32 Participants |
| Group 1 | Solicited General AEs | Fatigue: Related | 276 Participants |
| Group 1 | Solicited General AEs | Myalgia: Grade >=3 | 25 Participants |
| Group 1 | Solicited General AEs | Headache: Related | 279 Participants |
| Group 1 | Solicited General AEs | Pyrexia: Grade >=3 | 2 Participants |
| Group 2 | Solicited General AEs | Headache: Related | 314 Participants |
| Group 2 | Solicited General AEs | Chills: Any | 108 Participants |
| Group 2 | Solicited General AEs | Pyrexia: Grade >=3 | 4 Participants |
| Group 2 | Solicited General AEs | Chills: Related | 96 Participants |
| Group 2 | Solicited General AEs | Nausea: Any | 179 Participants |
| Group 2 | Solicited General AEs | Chills: Grade >=3 | 7 Participants |
| Group 2 | Solicited General AEs | Fatigue: Related | 279 Participants |
| Group 2 | Solicited General AEs | Headache: Any | 349 Participants |
| Group 2 | Solicited General AEs | Fatigue: Grade >=3 | 27 Participants |
| Group 2 | Solicited General AEs | Nausea: Related | 158 Participants |
| Group 2 | Solicited General AEs | Headache: Grade >=3 | 24 Participants |
| Group 2 | Solicited General AEs | Pyrexia: Related | 15 Participants |
| Group 2 | Solicited General AEs | Fatigue: Any | 303 Participants |
| Group 2 | Solicited General AEs | Myalgia: Any | 403 Participants |
| Group 2 | Solicited General AEs | Pyrexia: Any | 19 Participants |
| Group 2 | Solicited General AEs | Myalgia: Related | 381 Participants |
| Group 2 | Solicited General AEs | Nausea: Grade >=3 | 16 Participants |
| Group 2 | Solicited General AEs | Myalgia: Grade >=3 | 25 Participants |
| Group 3 | Solicited General AEs | Fatigue: Any | 287 Participants |
| Group 3 | Solicited General AEs | Pyrexia: Any | 14 Participants |
| Group 3 | Solicited General AEs | Pyrexia: Related | 14 Participants |
| Group 3 | Solicited General AEs | Pyrexia: Grade >=3 | 1 Participants |
| Group 3 | Solicited General AEs | Headache: Any | 354 Participants |
| Group 3 | Solicited General AEs | Headache: Related | 318 Participants |
| Group 3 | Solicited General AEs | Headache: Grade >=3 | 20 Participants |
| Group 3 | Solicited General AEs | Myalgia: Any | 431 Participants |
| Group 3 | Solicited General AEs | Myalgia: Related | 414 Participants |
| Group 3 | Solicited General AEs | Myalgia: Grade >=3 | 27 Participants |
| Group 3 | Solicited General AEs | Chills: Any | 90 Participants |
| Group 3 | Solicited General AEs | Chills: Related | 84 Participants |
| Group 3 | Solicited General AEs | Chills: Grade >=3 | 12 Participants |
| Group 3 | Solicited General AEs | Nausea: Any | 163 Participants |
| Group 3 | Solicited General AEs | Nausea: Related | 144 Participants |
| Group 3 | Solicited General AEs | Nausea: Grade >=3 | 16 Participants |
| Group 3 | Solicited General AEs | Fatigue: Related | 267 Participants |
| Group 3 | Solicited General AEs | Fatigue: Grade >=3 | 29 Participants |
| Group 4 | Solicited General AEs | Myalgia: Grade >=3 | 7 Participants |
| Group 4 | Solicited General AEs | Pyrexia: Related | 6 Participants |
| Group 4 | Solicited General AEs | Nausea: Related | 99 Participants |
| Group 4 | Solicited General AEs | Myalgia: Related | 156 Participants |
| Group 4 | Solicited General AEs | Pyrexia: Any | 9 Participants |
| Group 4 | Solicited General AEs | Nausea: Grade >=3 | 12 Participants |
| Group 4 | Solicited General AEs | Myalgia: Any | 172 Participants |
| Group 4 | Solicited General AEs | Headache: Grade >=3 | 21 Participants |
| Group 4 | Solicited General AEs | Headache: Related | 208 Participants |
| Group 4 | Solicited General AEs | Fatigue: Any | 201 Participants |
| Group 4 | Solicited General AEs | Headache: Any | 251 Participants |
| Group 4 | Solicited General AEs | Pyrexia: Grade >=3 | 0 Participants |
| Group 4 | Solicited General AEs | Fatigue: Grade >=3 | 13 Participants |
| Group 4 | Solicited General AEs | Chills: Grade >=3 | 3 Participants |
| Group 4 | Solicited General AEs | Chills: Related | 51 Participants |
| Group 4 | Solicited General AEs | Fatigue: Related | 176 Participants |
| Group 4 | Solicited General AEs | Nausea: Any | 128 Participants |
| Group 4 | Solicited General AEs | Chills: Any | 57 Participants |
Secondary
Solicited Local AEs
Incidence and intensity of solicited local AEs (redness, swelling, induration, pruritus and pain). Percentages based on subjects with at least one completed diary card.
Time frame: within 8 days after any vaccination
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Solicited Local AEs | Pain: Any | 846 Participants |
| Group 1 | Solicited Local AEs | Pain: Grade >=3 | 76 Participants |
| Group 1 | Solicited Local AEs | Erythema: Any | 597 Participants |
| Group 1 | Solicited Local AEs | Erythema: Grade >=3 | 15 Participants |
| Group 1 | Solicited Local AEs | Swelling: Any | 508 Participants |
| Group 1 | Solicited Local AEs | Swelling: Grade >=3 | 9 Participants |
| Group 1 | Solicited Local AEs | Induration: Any | 454 Participants |
| Group 1 | Solicited Local AEs | Induration: Grade >=3 | 4 Participants |
| Group 1 | Solicited Local AEs | Pruritis: Any | 430 Participants |
| Group 1 | Solicited Local AEs | Pruritis: Grade >=3 | 20 Participants |
| Group 2 | Solicited Local AEs | Erythema: Any | 610 Participants |
| Group 2 | Solicited Local AEs | Pruritis: Any | 424 Participants |
| Group 2 | Solicited Local AEs | Erythema: Grade >=3 | 18 Participants |
| Group 2 | Solicited Local AEs | Swelling: Any | 513 Participants |
| Group 2 | Solicited Local AEs | Swelling: Grade >=3 | 10 Participants |
| Group 2 | Solicited Local AEs | Induration: Any | 439 Participants |
| Group 2 | Solicited Local AEs | Pruritis: Grade >=3 | 15 Participants |
| Group 2 | Solicited Local AEs | Induration: Grade >=3 | 4 Participants |
| Group 2 | Solicited Local AEs | Pain: Any | 823 Participants |
| Group 2 | Solicited Local AEs | Pain: Grade >=3 | 66 Participants |
| Group 3 | Solicited Local AEs | Induration: Grade >=3 | 2 Participants |
| Group 3 | Solicited Local AEs | Induration: Any | 442 Participants |
| Group 3 | Solicited Local AEs | Pruritis: Grade >=3 | 13 Participants |
| Group 3 | Solicited Local AEs | Pain: Any | 830 Participants |
| Group 3 | Solicited Local AEs | Erythema: Grade >=3 | 12 Participants |
| Group 3 | Solicited Local AEs | Swelling: Grade >=3 | 4 Participants |
| Group 3 | Solicited Local AEs | Pruritis: Any | 414 Participants |
| Group 3 | Solicited Local AEs | Pain: Grade >=3 | 76 Participants |
| Group 3 | Solicited Local AEs | Swelling: Any | 499 Participants |
| Group 3 | Solicited Local AEs | Erythema: Any | 581 Participants |
| Group 4 | Solicited Local AEs | Swelling: Any | 55 Participants |
| Group 4 | Solicited Local AEs | Induration: Grade >=3 | 0 Participants |
| Group 4 | Solicited Local AEs | Swelling: Grade >=3 | 0 Participants |
| Group 4 | Solicited Local AEs | Pruritis: Grade >=3 | 2 Participants |
| Group 4 | Solicited Local AEs | Induration: Any | 45 Participants |
| Group 4 | Solicited Local AEs | Pain: Grade >=3 | 10 Participants |
| Group 4 | Solicited Local AEs | Erythema: Any | 173 Participants |
| Group 4 | Solicited Local AEs | Erythema: Grade >=3 | 0 Participants |
| Group 4 | Solicited Local AEs | Pain: Any | 187 Participants |
| Group 4 | Solicited Local AEs | Pruritis: Any | 115 Participants |
Secondary
Unsolicited Non-serious AEs: 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 | Unsolicited Non-serious AEs: Intensity | Total | 288 events |
| Group 1 | Unsolicited Non-serious AEs: Intensity | Grade 1 | 190 events |
| Group 1 | Unsolicited Non-serious AEs: Intensity | Grade 2 | 88 events |
| Group 1 | Unsolicited Non-serious AEs: Intensity | Grade 3 | 10 events |
| Group 1 | Unsolicited Non-serious AEs: Intensity | Grade 4 | 0 events |
| Group 1 | Unsolicited Non-serious AEs: Intensity | Missing | 0 events |
| Group 2 | Unsolicited Non-serious AEs: Intensity | Missing | 0 events |
| Group 2 | Unsolicited Non-serious AEs: Intensity | Grade 3 | 14 events |
| Group 2 | Unsolicited Non-serious AEs: Intensity | Total | 350 events |
| Group 2 | Unsolicited Non-serious AEs: Intensity | Grade 2 | 100 events |
| Group 2 | Unsolicited Non-serious AEs: Intensity | Grade 1 | 236 events |
| Group 2 | Unsolicited Non-serious AEs: Intensity | Grade 4 | 0 events |
| Group 3 | Unsolicited Non-serious AEs: Intensity | Grade 1 | 218 events |
| Group 3 | Unsolicited Non-serious AEs: Intensity | Grade 2 | 94 events |
| Group 3 | Unsolicited Non-serious AEs: Intensity | Grade 3 | 8 events |
| Group 3 | Unsolicited Non-serious AEs: Intensity | Missing | 0 events |
| Group 3 | Unsolicited Non-serious AEs: Intensity | Grade 4 | 0 events |
| Group 3 | Unsolicited Non-serious AEs: Intensity | Total | 320 events |
| Group 4 | Unsolicited Non-serious AEs: Intensity | Grade 4 | 0 events |
| Group 4 | Unsolicited Non-serious AEs: Intensity | Missing | 0 events |
| Group 4 | Unsolicited Non-serious AEs: Intensity | Grade 1 | 192 events |
| Group 4 | Unsolicited Non-serious AEs: Intensity | Grade 3 | 6 events |
| Group 4 | Unsolicited Non-serious AEs: Intensity | Total | 280 events |
| Group 4 | Unsolicited Non-serious AEs: Intensity | Grade 2 | 82 events |
Secondary
Unsolicited Non-serious AEs: 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 | Unsolicited Non-serious AEs: Relationship to Vaccination | Definite | 28 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Possible | 28 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Total | 288 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unlikely | 40 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Missing | 0 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unrelated/None | 187 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Probable | 5 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unrelated/None | 218 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Definite | 27 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Possible | 42 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Total | 350 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Probable | 6 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unlikely | 56 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Missing | 1 events |
| Group 3 | Unsolicited Non-serious AEs: Relationship to Vaccination | Probable | 7 events |
| Group 3 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unlikely | 61 events |
| Group 3 | Unsolicited Non-serious AEs: Relationship to Vaccination | Possible | 34 events |
| Group 3 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unrelated/None | 181 events |
| Group 3 | Unsolicited Non-serious AEs: Relationship to Vaccination | Definite | 35 events |
| Group 3 | Unsolicited Non-serious AEs: Relationship to Vaccination | Missing | 2 events |
| Group 3 | Unsolicited Non-serious AEs: Relationship to Vaccination | Total | 320 events |
| Group 4 | Unsolicited Non-serious AEs: Relationship to Vaccination | Possible | 29 events |
| Group 4 | Unsolicited Non-serious AEs: Relationship to Vaccination | Total | 280 events |
| Group 4 | Unsolicited Non-serious AEs: Relationship to Vaccination | Missing | 1 events |
| Group 4 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unrelated/None | 189 events |
| Group 4 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unlikely | 51 events |
| Group 4 | Unsolicited Non-serious AEs: Relationship to Vaccination | Definite | 4 events |
| Group 4 | Unsolicited Non-serious AEs: Relationship to Vaccination | Probable | 6 events |