Smallpox
Conditions
Brief summary
A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Evaluate Safety and Immunogenicity of One and Two Doses of IMVAMUNE® Smallpox Vaccine in 56-80 Year Old Vaccinia-Experienced Subjects
Interventions
BIOLOGICALIMVAMUNE
Two s.c. vaccinations with 0.5 ml IMVAMUNE® vaccine containing 1 x 10E8 TCID50 / dose
Sponsors
Bavarian Nordic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
56 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female subjects 56-70 years of age. If no safety concerns are identified upon review of the safety data from the first 30 subjects enrolled, the age range is extended up to 80 years. * Time since most current smallpox vaccination \> 10 years. * The subject has read, signed and dated the Informed Consent Form (ICF), successfully completed (at least 90% correct \[no more than 3 attempts allowed\]) the test of understanding and has signed the Health Insurance Portability and Accountability Act (HIPAA) authorization form. * Women must have a negative serum pregnancy test at screening and negative urine pregnancy test within 24 hours prior to vaccination. * 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 study and must not plan to become pregnant for at least 28 days after the last vaccination. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products). * Weight: ≥ 100 pounds (45.5 kg) and ≤ 330 pounds (150 kg). * White blood cells ≥ 2500/mm3 and \< 11,000/mm3. * Absolute neutrophil count within normal limits. * Hemoglobin within normal limits. * Platelets within normal limits. * Adequate renal function defined as: 1. Urine protein ≤ +1 (by dip stick) 2. Serum creatinine within normal limits * 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. 2. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 1.5 x ULN. * Cardiac 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, sustained atrial arrhythmias, sustained ventricular arrhythmia, 2 premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia.
Exclusion criteria
* History of or active immunodeficiency or immuno-suppression caused by acquired or congenital diseases or caused by treatments such as chronic administration (\> 14 days) of systemic, i.e. parenteral or oral, corticosteroids (\> 5 mg prednisone \[or equivalent\] per day), radiation or immune-modifying drugs. * Periodic steroid injections, e.g. intraarticular, are not allowed within 30 days prior to the first vaccination and throughout the study until Visit 5 (V5). * Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy. * 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 prevent the subject from complying with study requirements. * History of or active autoimmune disease, e.g. Type I diabetes. Persons with vitiligo or thyroid disease taking thyroid hormone replacement are not excluded. * Skin cancer in the past six months. If treatment for skin cancer was successfully completed more than six months ago and the malignancy is considered to be cured, the subject may be enrolled. Subjects with history of skin cancer must not be vaccinated at the previous site of cancer. * Any other malignancy in the past five years. If treatment for cancer was successfully completed more than 5 years ago and the malignancy is considered to be cured, the subject may be enrolled. * Clinically significant hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders which are not adequately controlled by medical treatment within the last 12 weeks before vaccination as judged by the site's Principal Investigator. * History of myocardial infarction, congestive heart failure with marked limitation of activity due to symptoms, e.g. walking short distances \[20 100 m\] (i.e. \> Grade II according to the New York Heart Association), cardiomyopathy and stroke or transient ischemic attack in the past two years. * Uncontrolled high blood pressure defined as systolic blood pressure ≥ 150 mm Hg and/or ≥ diastolic blood pressure ≥ 100 mm Hg within the last six months. * Subjects with active coronary heart disease manifested by angina, even if on medication. * 25 % 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 * Clinically significant mental disorder not adequately controlled by medical treatment. * History of chronic alcohol abuse (40 g/day, e.g. 3 glasses of beer or 2 glasses of wine for at least six months) and/or intravenous drug abuse (within the last six months). Subjects with a history of other substance and/or alcohol abuse are also excluded if - in the opinion of the investigator - the abuse could prevent the subject from complying with study requirements. * History of allergic disease or reactions likely to be exacerbated by IMVAMUNE® or any component of the vaccine, e.g. tris(hydroxymethyl)-amino methane, chicken embryo fibroblast proteins, aminoglycosides (gentamycin). * History of anaphylactic shock or any severe allergic reaction to a vaccine requiring immediate treatment. * Subjects undergoing treatment for tuberculosis infection or disease. * Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior to or after study vaccination. * Having received any vaccinations or planned vaccinations with a killed vaccine within 14 days prior to or after study vaccination. * Administration or planned administration of immuno-globulins and/or any blood products during a period starting from three 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 the first dose of the study vaccine or planned administration of such a drug during the study period. * Temperature ≥ 100.4°F (38.0°C) at the time of enrollment. * Any condition which might interfere with study objectives or would limit the subject's ability to complete the study in the opinion of the investigator. * Study personnel.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Related Serious Adverse Events | within 8 weeks | Incidence of Serious Adverse Events (SAEs) probably, possibly or definitely related to the trial vaccine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Unsolicited Non-serious AEs: Relationship to Vaccination | within 29 days after any vaccination | Occurrence of unsolicited non-serious AEs by relationship to study vaccine |
| 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) and unsolicited AEs |
| Cardiac Signs or Symptoms | within 32 weeks | Incidence, relationship and intensity of any cardiac sign or symptom indicating a case of myo-/pericarditis (AESI). AESIs were defined as any cardiac symptoms and ECG changes determined to be clinically significant or cardiac enzymes elevated above 2 x upper limit of normal range (ULN). |
| Solicited Local Adverse Events | within 8 days after any vaccination | Incidence and intensity of solicited local AEs (pain, erythema, swelling, induration, and pruritus). Percentages based on subjects with at least one completed diary card. |
| Solicited General Adverse Events | within 8 days after any vaccination | Incidence of solicited general AEs (body temperature increased, headache, myalgia, chills, nausea, and fatigue): Intensity and relationship tovaccination. Percentages based on subjects with at least one completed diary card. |
| ELISA Response Rate | within 32 weeks | Response rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Response is defined as the 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 response rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available. |
| Unsolicited Non-serious AEs: Intensity | within 29 days after any vaccination | Occurrence of unsolicited non-serious AEs by Intensity |
| ELISA GMT | within 32 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 8 weeks (end of active trial phase). Titers below the detection limit are included with a value of '1'. |
| PRNT Response Rate | within 32 weeks | Response rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Response is defined as the appearance of antibody titers ≥ detection limit (15) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual peak response rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available. |
| PRNT Seroconversion Rate | within 32 weeks | Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (15) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual peak seroconversion rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available. |
| PRNT GMT | within 32 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 8 weeks (end of active trial phase). Titers below the detection limit are included with a value of '1'. |
| Correlation PRNT vs ELISA Titers | within 32 weeks | Pearson Correlation Coefficient between the log10 transformed PRNT titers and the log10 transformed ELISA titers |
| ELISA Seroconversion Rate | within 32 weeks | Seroconversion rate based on vaccinia-specific 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. Individual peak seroconversion rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 IMVAMUNE: Two s.c. vaccinations with 0.5 ml IMVAMUNE® vaccine containing 1 x 10E8 TCID50 / dose | 62 |
| Group 2 IMVAMUNE: One s.c. vaccination with placebo (0.5 ml saline), followed by a second s.c. vaccination with 0.5 ml IMVAMUNE® vaccine containing 1 x 10E8 TCID50 | 58 |
| Total | 120 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Total |
|---|---|---|---|
| Age, Continuous | 64.6 years STANDARD_DEVIATION 5.41 | 62.6 years STANDARD_DEVIATION 5.85 | 63.7 years STANDARD_DEVIATION 5.7 |
| Sex: Female, Male Female | 37 Participants | 40 Participants | 77 Participants |
| Sex: Female, Male Male | 25 Participants | 18 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 58 |
| other Total, other adverse events | 21 / 62 | 21 / 58 |
| serious Total, serious adverse events | 2 / 62 | 2 / 58 |
Outcome results
Primary
Related Serious Adverse Events
Incidence of Serious Adverse Events (SAEs) probably, possibly or definitely related to the trial vaccine
Time frame: within 8 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Related Serious Adverse Events | 0 Participants |
| Group 2 | Related Serious Adverse Events | 0 Participants |
Secondary
Cardiac Signs or Symptoms
Incidence, relationship and intensity of any cardiac sign or symptom indicating a case of myo-/pericarditis (AESI). AESIs were defined as any cardiac symptoms and ECG changes determined to be clinically significant or cardiac enzymes elevated above 2 x upper limit of normal range (ULN).
Time frame: within 32 weeks
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Cardiac Signs or Symptoms | Any AESI | 5 Participants |
| Group 1 | Cardiac Signs or Symptoms | Any AESI with intensity >= Grade 3 | 0 Participants |
| Group 1 | Cardiac Signs or Symptoms | Any AESI assessed as related to vaccine | 0 Participants |
| Group 2 | Cardiac Signs or Symptoms | Any AESI | 0 Participants |
| Group 2 | Cardiac Signs or Symptoms | Any AESI with intensity >= Grade 3 | 0 Participants |
| Group 2 | Cardiac Signs or Symptoms | Any AESI assessed as related to vaccine | 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: within 32 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Correlation PRNT vs ELISA Titers | Week 4 | 0.569 Pearson correlation coefficient |
| Group 1 | Correlation PRNT vs ELISA Titers | Week 32 | 0.500 Pearson correlation coefficient |
| Group 1 | Correlation PRNT vs ELISA Titers | Week 6 | 0.660 Pearson correlation coefficient |
| Group 1 | Correlation PRNT vs ELISA Titers | Week 8 | 0.600 Pearson correlation coefficient |
| Group 1 | Correlation PRNT vs ELISA Titers | Week 2 | 0.704 Pearson correlation coefficient |
| Group 2 | Correlation PRNT vs ELISA Titers | Week 8 | 0.616 Pearson correlation coefficient |
| Group 2 | Correlation PRNT vs ELISA Titers | Week 2 | 0.489 Pearson correlation coefficient |
| Group 2 | Correlation PRNT vs ELISA Titers | Week 4 | 0.492 Pearson correlation coefficient |
| Group 2 | Correlation PRNT vs ELISA Titers | Week 6 | 0.697 Pearson correlation coefficient |
| Group 2 | Correlation PRNT vs ELISA Titers | Week 32 | 0.654 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 8 weeks (end of active trial phase). Titers below the detection limit are included with a value of '1'.
Time frame: within 32 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 | ELISA GMT | Week 4 | 501.2 Titer |
| Group 1 | ELISA GMT | Week 8 | 720.2 Titer |
| Group 1 | ELISA GMT | Week 2 | 622.5 Titer |
| Group 1 | ELISA GMT | Individual Peak | 992.4 Titer |
| Group 1 | ELISA GMT | Week 6 | 804.1 Titer |
| Group 1 | ELISA GMT | Week 32 | 344.6 Titer |
| Group 1 | ELISA GMT | Week 0 | 129.0 Titer |
| Group 2 | ELISA GMT | Week 32 | 258.1 Titer |
| Group 2 | ELISA GMT | Week 0 | 105.3 Titer |
| Group 2 | ELISA GMT | Week 2 | 98.5 Titer |
| Group 2 | ELISA GMT | Week 4 | 101.0 Titer |
| Group 2 | ELISA GMT | Week 6 | 605.8 Titer |
| Group 2 | ELISA GMT | Week 8 | 505.0 Titer |
| Group 2 | ELISA GMT | Individual Peak | 645.2 Titer |
Secondary
ELISA Response Rate
Response rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Response is defined as the 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 response rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available.
Time frame: within 32 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | ELISA Response Rate | Week 2 | 98.4 percentage of subjects |
| Group 1 | ELISA Response Rate | Week 4 | 96.6 percentage of subjects |
| Group 1 | ELISA Response Rate | Week 6 | 98.3 percentage of subjects |
| Group 1 | ELISA Response Rate | Week 8 | 100.0 percentage of subjects |
| Group 1 | ELISA Response Rate | Individual Peak | 100.0 percentage of subjects |
| Group 1 | ELISA Response Rate | Week 32 | 94.9 percentage of subjects |
| Group 2 | ELISA Response Rate | Individual Peak | 100.0 percentage of subjects |
| Group 2 | ELISA Response Rate | Week 2 | 19.0 percentage of subjects |
| Group 2 | ELISA Response Rate | Week 8 | 100.0 percentage of subjects |
| Group 2 | ELISA Response Rate | Week 4 | 19.0 percentage of subjects |
| Group 2 | ELISA Response Rate | Week 32 | 82.8 percentage of subjects |
| Group 2 | ELISA Response Rate | Week 6 | 96.6 percentage of subjects |
Secondary
ELISA Seroconversion Rate
Seroconversion rate based on vaccinia-specific 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. Individual peak seroconversion rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available.
Time frame: within 32 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | ELISA Seroconversion Rate | Week 2 | 83.6 percentage of subjects |
| Group 1 | ELISA Seroconversion Rate | Week 4 | 79.7 percentage of subjects |
| Group 1 | ELISA Seroconversion Rate | Week 6 | 83.3 percentage of subjects |
| Group 1 | ELISA Seroconversion Rate | Week 8 | 83.1 percentage of subjects |
| Group 1 | ELISA Seroconversion Rate | Individual Peak | 90.2 percentage of subjects |
| Group 1 | ELISA Seroconversion Rate | Week 32 | 59.3 percentage of subjects |
| Group 2 | ELISA Seroconversion Rate | Individual Peak | 84.5 percentage of subjects |
| Group 2 | ELISA Seroconversion Rate | Week 2 | 1.7 percentage of subjects |
| Group 2 | ELISA Seroconversion Rate | Week 8 | 77.6 percentage of subjects |
| Group 2 | ELISA Seroconversion Rate | Week 4 | 3.4 percentage of subjects |
| Group 2 | ELISA Seroconversion Rate | Week 32 | 58.6 percentage of subjects |
| Group 2 | ELISA Seroconversion Rate | Week 6 | 82.8 percentage of subjects |
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 8 weeks (end of active trial phase). Titers below the detection limit are included with a value of '1'.
Time frame: within 32 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 | PRNT GMT | Week 8 | 144.9 Titer |
| Group 1 | PRNT GMT | Week 0 | 11.9 Titer |
| Group 1 | PRNT GMT | Week 2 | 111.4 Titer |
| Group 1 | PRNT GMT | Week 4 | 79.5 Titer |
| Group 1 | PRNT GMT | Week 6 | 210.3 Titer |
| Group 1 | PRNT GMT | Individual Peak | 257.6 Titer |
| Group 1 | PRNT GMT | Week 32 | 47.0 Titer |
| Group 2 | PRNT GMT | Individual Peak | 139.6 Titer |
| Group 2 | PRNT GMT | Week 6 | 126.7 Titer |
| Group 2 | PRNT GMT | Week 0 | 11.3 Titer |
| Group 2 | PRNT GMT | Week 8 | 99.5 Titer |
| Group 2 | PRNT GMT | Week 2 | 9.2 Titer |
| Group 2 | PRNT GMT | Week 32 | 27.6 Titer |
| Group 2 | PRNT GMT | Week 4 | 11.3 Titer |
Secondary
PRNT Response Rate
Response rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Response is defined as the appearance of antibody titers ≥ detection limit (15) for initially seronegative subjects, or an increase of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual peak response rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available.
Time frame: within 32 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | PRNT Response Rate | Week 2 | 83.6 percentage of subjects |
| Group 1 | PRNT Response Rate | Week 4 | 81.4 percentage of subjects |
| Group 1 | PRNT Response Rate | Week 6 | 96.7 percentage of subjects |
| Group 1 | PRNT Response Rate | Week 8 | 89.8 percentage of subjects |
| Group 1 | PRNT Response Rate | Individual Peak | 96.7 percentage of subjects |
| Group 1 | PRNT Response Rate | Week 32 | 66.1 percentage of subjects |
| Group 2 | PRNT Response Rate | Individual Peak | 84.5 percentage of subjects |
| Group 2 | PRNT Response Rate | Week 2 | 15.5 percentage of subjects |
| Group 2 | PRNT Response Rate | Week 8 | 79.3 percentage of subjects |
| Group 2 | PRNT Response Rate | Week 4 | 10.3 percentage of subjects |
| Group 2 | PRNT Response Rate | Week 32 | 50.0 percentage of subjects |
| Group 2 | PRNT Response Rate | Week 6 | 82.8 percentage of subjects |
Secondary
PRNT Seroconversion Rate
Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (15) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Individual peak seroconversion rate is based on the maximum post-Baseline antibody titer within 8 weeks (end of active trial phase). Percentages based on number of subjects with data available.
Time frame: within 32 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | PRNT Seroconversion Rate | Week 2 | 73.8 percentage of subjects |
| Group 1 | PRNT Seroconversion Rate | Week 4 | 71.2 percentage of subjects |
| Group 1 | PRNT Seroconversion Rate | Week 6 | 90.0 percentage of subjects |
| Group 1 | PRNT Seroconversion Rate | Week 8 | 86.4 percentage of subjects |
| Group 1 | PRNT Seroconversion Rate | Individual Peak | 95.1 percentage of subjects |
| Group 1 | PRNT Seroconversion Rate | Week 32 | 55.9 percentage of subjects |
| Group 2 | PRNT Seroconversion Rate | Individual Peak | 77.6 percentage of subjects |
| Group 2 | PRNT Seroconversion Rate | Week 2 | 10.3 percentage of subjects |
| Group 2 | PRNT Seroconversion Rate | Week 8 | 74.1 percentage of subjects |
| Group 2 | PRNT Seroconversion Rate | Week 4 | 8.6 percentage of subjects |
| Group 2 | PRNT Seroconversion Rate | Week 32 | 41.4 percentage of subjects |
| Group 2 | PRNT Seroconversion Rate | Week 6 | 77.6 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) and unsolicited AEs
Time frame: within 29 days after any vaccination
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Related Grade >=3 Adverse Events | 3 Participants |
| Group 2 | Related Grade >=3 Adverse Events | 1 Participants |
Secondary
Solicited General Adverse Events
Incidence of solicited general AEs (body temperature increased, headache, myalgia, chills, nausea, and fatigue): Intensity and relationship tovaccination. Percentages based on subjects with at least one completed diary card.
Time frame: within 8 days after any vaccination
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Solicited General Adverse Events | Increased body temperature: Any | 2 Participants |
| Group 1 | Solicited General Adverse Events | Increased body temperature: Related | 2 Participants |
| Group 1 | Solicited General Adverse Events | Increased body temperature: Grade >=3 | 0 Participants |
| Group 1 | Solicited General Adverse Events | Headache: Any | 19 Participants |
| Group 1 | Solicited General Adverse Events | Headache: Related | 15 Participants |
| Group 1 | Solicited General Adverse Events | Headache: Grade >=3 | 1 Participants |
| Group 1 | Solicited General Adverse Events | Myalgia: Any | 19 Participants |
| Group 1 | Solicited General Adverse Events | Myalgia: Related | 14 Participants |
| Group 1 | Solicited General Adverse Events | Chills: Any | 5 Participants |
| Group 1 | Solicited General Adverse Events | Chills: Related | 5 Participants |
| Group 1 | Solicited General Adverse Events | Chills: Grade >=3 | 0 Participants |
| Group 1 | Solicited General Adverse Events | Nausea: Any | 7 Participants |
| Group 1 | Solicited General Adverse Events | Nausea: Related | 4 Participants |
| Group 1 | Solicited General Adverse Events | Nausea: Grade >=3 | 0 Participants |
| Group 1 | Solicited General Adverse Events | Fatigue: Any | 21 Participants |
| Group 1 | Solicited General Adverse Events | Fatigue: Related | 18 Participants |
| Group 1 | Solicited General Adverse Events | Fatigue: Grade >=3 | 1 Participants |
| Group 1 | Solicited General Adverse Events | Myalgia: Grade >=3 | 2 Participants |
| Group 2 | Solicited General Adverse Events | Nausea: Grade >=3 | 0 Participants |
| Group 2 | Solicited General Adverse Events | Increased body temperature: Any | 1 Participants |
| Group 2 | Solicited General Adverse Events | Chills: Related | 1 Participants |
| Group 2 | Solicited General Adverse Events | Increased body temperature: Related | 0 Participants |
| Group 2 | Solicited General Adverse Events | Myalgia: Grade >=3 | 1 Participants |
| Group 2 | Solicited General Adverse Events | Increased body temperature: Grade >=3 | 0 Participants |
| Group 2 | Solicited General Adverse Events | Chills: Grade >=3 | 0 Participants |
| Group 2 | Solicited General Adverse Events | Headache: Any | 22 Participants |
| Group 2 | Solicited General Adverse Events | Fatigue: Any | 18 Participants |
| Group 2 | Solicited General Adverse Events | Headache: Related | 14 Participants |
| Group 2 | Solicited General Adverse Events | Nausea: Any | 5 Participants |
| Group 2 | Solicited General Adverse Events | Headache: Grade >=3 | 0 Participants |
| Group 2 | Solicited General Adverse Events | Fatigue: Grade >=3 | 0 Participants |
| Group 2 | Solicited General Adverse Events | Myalgia: Any | 14 Participants |
| Group 2 | Solicited General Adverse Events | Nausea: Related | 4 Participants |
| Group 2 | Solicited General Adverse Events | Myalgia: Related | 12 Participants |
| Group 2 | Solicited General Adverse Events | Fatigue: Related | 15 Participants |
| Group 2 | Solicited General Adverse Events | Chills: Any | 4 Participants |
Secondary
Solicited Local Adverse Events
Incidence and intensity of solicited local AEs (pain, erythema, swelling, induration, and pruritus). Percentages based on subjects with at least one completed diary card.
Time frame: within 8 days after any vaccination
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Solicited Local Adverse Events | Erythema: Grade >=3 | 3 Participants |
| Group 1 | Solicited Local Adverse Events | Induration: Any | 31 Participants |
| Group 1 | Solicited Local Adverse Events | Erythema: Any | 49 Participants |
| Group 1 | Solicited Local Adverse Events | Induration: Grade >=3 | 0 Participants |
| Group 1 | Solicited Local Adverse Events | Swelling: Any | 39 Participants |
| Group 1 | Solicited Local Adverse Events | Pruritis: Any | 27 Participants |
| Group 1 | Solicited Local Adverse Events | Pain: Grade >=3 | 4 Participants |
| Group 1 | Solicited Local Adverse Events | Pruritis: Grade >=3 | 0 Participants |
| Group 1 | Solicited Local Adverse Events | Swelling: Grade >=3 | 0 Participants |
| Group 1 | Solicited Local Adverse Events | Pain: Any | 46 Participants |
| Group 2 | Solicited Local Adverse Events | Swelling: Grade >=3 | 0 Participants |
| Group 2 | Solicited Local Adverse Events | Pain: Grade >=3 | 1 Participants |
| Group 2 | Solicited Local Adverse Events | Erythema: Any | 37 Participants |
| Group 2 | Solicited Local Adverse Events | Erythema: Grade >=3 | 1 Participants |
| Group 2 | Solicited Local Adverse Events | Swelling: Any | 27 Participants |
| Group 2 | Solicited Local Adverse Events | Pain: Any | 36 Participants |
| Group 2 | Solicited Local Adverse Events | Induration: Any | 17 Participants |
| Group 2 | Solicited Local Adverse Events | Induration: Grade >=3 | 0 Participants |
| Group 2 | Solicited Local Adverse Events | Pruritis: Any | 22 Participants |
| Group 2 | Solicited Local Adverse Events | Pruritis: Grade >=3 | 0 Participants |
Secondary
Unsolicited Non-serious AEs: Intensity
Occurrence of unsolicited non-serious AEs by Intensity
Time frame: within 29 days after any vaccination
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Unsolicited Non-serious AEs: Intensity | Total | 73 events |
| Group 1 | Unsolicited Non-serious AEs: Intensity | Grade 1 | 60 events |
| Group 1 | Unsolicited Non-serious AEs: Intensity | Grade 2 | 9 events |
| Group 1 | Unsolicited Non-serious AEs: Intensity | Grade 3 | 4 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 | Grade 4 | 0 events |
| Group 2 | Unsolicited Non-serious AEs: Intensity | Total | 58 events |
| Group 2 | Unsolicited Non-serious AEs: Intensity | Grade 3 | 1 events |
| Group 2 | Unsolicited Non-serious AEs: Intensity | Grade 1 | 50 events |
| Group 2 | Unsolicited Non-serious AEs: Intensity | Missing | 0 events |
| Group 2 | Unsolicited Non-serious AEs: Intensity | Grade 2 | 7 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: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Possible | 20 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Definite | 7 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unlikely | 6 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Missing | 0 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Probable | 8 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Total | 73 events |
| Group 1 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unrelated/None | 32 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Total | 58 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unrelated/None | 26 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Unlikely | 2 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Possible | 13 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Probable | 5 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Definite | 12 events |
| Group 2 | Unsolicited Non-serious AEs: Relationship to Vaccination | Missing | 0 events |