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| Name | Class |
|---|---|
| US Army Medical Research Institute of Infectious Diseases | FED |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Experimental | 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). |
|
| Group 2 | Active Comparator | A single vaccination of ACAM2000® will be administered at Day 0. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MVA BN® | Biological | 0.5 ml MVA BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 42 for Group 1 and Day 28 for Group 2 |
| 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). | Day 6-8, 13-15 after 3rd Vaccination for Group 1 and Day 6-8, 13-15 after 1st vaccination for Group 2 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | Day 6-8 and Day 13-15 after ACAM2000 scarification |
| Investigator-measured Lesion Diameter in mm at Day 6-8 After Scarification With ACAM2000 |
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Inclusion Criteria:
Healthy male and female subjects, 18-42 years of age
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
Acceptable medical history by screening evaluation and physical examination
BMI greater or eaqual than 18.5 and smaller than 35
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
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)
Human Immunodeficiency Virus (HIV) antibody negative, hepatitis B surface antigen negative and negative antibody test to hepatitis C virus
White blood cells greater or eaqual than 2500/mm3 and smaller than 11,000/mm3
Hemoglobin within normal limits
Platelets greater or eaqual than lower normal limits
Adequate renal function defined as a calculated Creatinine Clearance (CrCl) greater than 60 ml/min as estimated by the Cockcroft-Gault equation
Adequate hepatic function in the absence of other evidence of significant liver disease defined as:
Troponin I smaller than 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, 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:
Pregnant or breast-feeding women
Typical vaccinia scar
Known or suspected history of smallpox vaccination defined as visible vaccination scar or documentation of smallpox vaccination or as reported by the subject
History of vaccination with any poxvirus-based vaccine
History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject
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
Having had radiation or X-ray treatment (not routine X-rays) within the last 3 months
Post organ and bone-marrow transplant subjects whether or not receiving chronic immunosuppressive therapy
Eye surgery within 4 weeks prior to trial vaccination
History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid hormone replacement are not excluded
Uncontrolled serious infection, i.e. not responding to antimicrobial therapy
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
History of keloid formation
History or clinical manifestation of severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders
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
Chest pain (that is diagnosed as cardiac related) or trouble breathing on exertion
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
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
Clinically significant psychological disorder not adequately controlled by medical treatment
Active or history of chronic alcohol abuse and/or intravenous and/or nasal drug abuse (within the past 6 months)
History of anaphylaxis or any severe allergic reaction or serious adverse reaction to a vaccine
Eczema of any degree or history of eczema
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
People with chronic exfoliative skin disorders/conditions
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
People with a tattoo that covers the vaccination injection area (preventing assessment of the area and interfering with a vaccination site photograph)
Having received any vaccinations or planned vaccinations with a live vaccine within 28 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
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
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
Blood donation for the duration of the trial
Acute disease (illness with or without a fever) at the time of enrollment
Temperature ≥ 100.4°F (38.0°C) at the time of enrollment
Known household contacts with, or occupational exposure (other than minimal contact) to any of the following:
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)
Known allergies to ACAM2000® and its diluents including polymyxin B sulfate, neomycin sulfate, and phenol
Known allergies to vaccinia immunoglobulin (VIG) including thimerosal or previous allergic reaction to immunoglobulins
Known allergies to cidofovir, sulfa drugs, or probenecid
Trial personnel
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| Name | Affiliation | Role |
|---|---|---|
| Phillip R Pittman, MD, MPH | US Army Medical Research Institute of Infectious Diseases | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brian Allgood Army Community Hospital | Seoul | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31722150 | Derived | Pittman PR, Hahn M, Lee HS, Koca C, Samy N, Schmidt D, Hornung J, Weidenthaler H, Heery CR, Meyer TPH, Silbernagl G, Maclennan J, Chaplin P. Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox. N Engl J Med. 2019 Nov 14;381(20):1897-1908. doi: 10.1056/NEJMoa1817307. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 titer 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Full Analysis Set
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Per-protocol Set for Immunogenicity | Posted | Geometric Mean | 95% Confidence Interval | Titer | Day 42 for Group 1 and Day 28 for Group 2 |
|
38 weeks for Group 1 and 30 weeks for Group 2
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1, Period 1 | after 1st dose of MVA-BN | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Program Lead, Clinical Operations | Bavarian Nordic A/S | +45 3326 | 8383 | info@bavarian-nordic.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan: Edition 8 | Mar 21, 2016 | Nov 15, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Sep 29, 2016 | Nov 15, 2019 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Edition 8, Amendment 1 | Oct 11, 2017 | Nov 15, 2019 | SAP_002.pdf |
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| ID | Term |
|---|---|
| C527606 | smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic |
| C000588544 | ACAM2000 |
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| ACAM2000® | Biological | 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. |
|
The lesion diameter at Day 6-8 was defined as the major lesion diameter measured on Day 6-8 (after scarification) |
| Day 6-8 after ACAM2000 scarification |
| 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) | Day 13-15 after ACAM2000 scarification |
| 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). | Day 6-8 visit following ACAM2000 vaccination |
| 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. | Day 6-8 after ACAM2000 scarification |
| 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. | Day 13-15 after ACAM2000 scarification |
| Relationship to Vaccine of Any Serious Adverse Event (SAE) | Presentation of SAEs by relationship to study vaccine | Within 38 weeks for Group 1 and 30 weeks for Group 2 |
| Intensity of Any Serious Adverse Event (SAE) | Presentation of SAEs by intensity | Within 38 weeks for Group 1 and 30 weeks for Group 2 |
| 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. | Within 38 weeks for Group 1 and 30 weeks for Group 2 |
| 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. | within 29 days after vaccination |
| Relationship to Vaccine of Any Non-serious AEs | Presentation of non-serious AEs by relationship to study vaccine | within 29 days after vaccination |
| Intensity of Any Non-serious AEs | Presentation of non-serious AEs by intensity | within 29 days after vaccination |
| Solicited General AEs | Occurrence, intensity and relationship of solicited general AEs (body temperature [fever], headache, myalgia [muscle pain], chills, nausea, fatigue, malaise) | within 15 days after vaccination |
| Incidence of Lymphadenopathy | Incidence of events of Lymphadenopathy. Pooled solicited and unsolicited events. | within 29 days after vaccination |
| Solicited Local AEs: Intensity | Incidence of solicited local AEs (pain, redness [erythema], swelling, induration, itching [pruritus]) | within 15 days after vaccination |
| 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. | Within 15 days after scarification with ACAM2000 |
| 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. | within 8 weeks (for both groups) |
| 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. | within 8 weeks (for both groups) |
| 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'. | within 12 weeks |
| 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'. | within 12 weeks |
| 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. | Group 1 at Week 6; Group 2 at Week 4 |
| 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. | Group 1 at Week 6; Group 2 at Week 4 |
| Withdrawal by Subject |
|
| multiple reasons |
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 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. |
|
|
|
| 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). | Per-protocol Set | Posted | Median | 95% Confidence Interval | mm2 | Day 6-8, 13-15 after 3rd Vaccination for Group 1 and Day 6-8, 13-15 after 1st vaccination for Group 2 |
|
|
|
|
| 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) | Per-protocol Set | Posted | Median | 95% Confidence Interval | mm | Day 6-8 and Day 13-15 after ACAM2000 scarification |
|
|
|
| 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) | Per-protocol Set | Posted | Median | 95% Confidence Interval | mm | Day 6-8 after ACAM2000 scarification |
|
|
|
| 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) | Per-protocol Set | Posted | Median | 95% Confidence Interval | mm | Day 13-15 after ACAM2000 scarification |
|
|
|
| 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). | Per-protocol Set | Posted | Number | 95% Confidence Interval | percentage of subjects | Day 6-8 visit following ACAM2000 vaccination |
|
|
|
| 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. | Per-protocol Set | Posted | Median | 95% Confidence Interval | mm2 | Day 6-8 after ACAM2000 scarification |
|
|
|
| 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. | Per-protocol Set | Posted | Median | 95% Confidence Interval | mm2 | Day 13-15 after ACAM2000 scarification |
|
|
|
| Secondary | Relationship to Vaccine of Any Serious Adverse Event (SAE) | Presentation of SAEs by relationship to study vaccine | Full Analysis Set | Posted | Number | Events | Within 38 weeks for Group 1 and 30 weeks for Group 2 |
|
|
|
| Secondary | Intensity of Any Serious Adverse Event (SAE) | Presentation of SAEs by intensity | Full Analysis Set | Posted | Number | participants | Within 38 weeks for Group 1 and 30 weeks for Group 2 |
|
|
|
| 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. | Full Analysis Set | Posted | Count of Participants | Participants | Within 38 weeks for Group 1 and 30 weeks for Group 2 |
|
|
|
| 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. | Full Analysis Set | Posted | Count of Participants | Participants | within 29 days after vaccination |
|
|
|
| Secondary | Relationship to Vaccine of Any Non-serious AEs | Presentation of non-serious AEs by relationship to study vaccine | Full Analysis Set | Posted | Number | Events | within 29 days after vaccination |
|
|
|
| Secondary | Intensity of Any Non-serious AEs | Presentation of non-serious AEs by intensity | Full Analysis Set | Posted | Number | Events | within 29 days after vaccination |
|
|
|
| Secondary | Solicited General AEs | Occurrence, intensity and relationship of solicited general AEs (body temperature [fever], headache, myalgia [muscle pain], chills, nausea, fatigue, malaise) | Full Analysis Set | Posted | Count of Participants | Participants | within 15 days after vaccination |
|
|
|
| Secondary | Incidence of Lymphadenopathy | Incidence of events of Lymphadenopathy. Pooled solicited and unsolicited events. | Full Analysis Set | Posted | Count of Participants | Participants | within 29 days after vaccination |
|
|
|
| Secondary | Solicited Local AEs: Intensity | Incidence of solicited local AEs (pain, redness [erythema], swelling, induration, itching [pruritus]) | Full Analysis Set | Posted | Count of Participants | Participants | within 15 days after vaccination |
|
|
|
| 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. | Full Analysis Set | Posted | Median | 95% Confidence Interval | mm | Within 15 days after scarification with ACAM2000 |
|
|
|
| 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. | Per-protocol Set for Immunogenicity | Posted | Geometric Mean | 95% Confidence Interval | Titer | within 8 weeks (for both groups) |
|
|
|
| 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. | Per-protocol Set for Immunogenicity | Posted | Geometric Mean | 95% Confidence Interval | Titer | within 8 weeks (for both groups) |
|
|
|
| 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'. | Per-protocol Set for Immunogenicity | Posted | Geometric Mean | 95% Confidence Interval | Titer | within 12 weeks |
|
|
|
| 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'. | Per-protocol Set for Immunogenicity | Posted | Geometric Mean | 95% Confidence Interval | Titer | within 12 weeks |
|
|
|
| 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. | Per-protocol Set for Immunogenicity | Posted | Number | 95% Confidence Interval | percentage of subjects | Group 1 at Week 6; Group 2 at Week 4 |
|
|
|
| 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. | Per-protocol Set for Immunogenicity | Posted | Number | 95% Confidence Interval | percentage of subjects | Group 1 at Week 6; Group 2 at Week 4 |
|
|
|
| 220 |
| 2 |
| 220 |
| 95 |
| 220 |
| EG001 | Group 1, Period 2 | after 2nd dose of MVA-BN | 0 | 208 | 0 | 208 | 63 | 208 |
| EG002 | Group 1, Period 3 | after ACAM2000 | 0 | 196 | 3 | 196 | 79 | 196 |
| EG003 | Group 2 | ACAM2000 | 0 | 213 | 3 | 213 | 88 | 213 |
| Suicidal Ideation | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
|
| Alcohol Poisoning | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Peritonsillar Abscess | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Road Traffic Accident | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Tibia Fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Axillary Pain | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Injection Site Erythema | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Injection Site Nodule | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Vaccination Site Erythema | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Vaccination Site Nodule | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Vaccination Site Warmth | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dermatitis Contact | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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Not provided
Not provided
| Absent Take |
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| Missing |
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| Possible |
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| Probable |
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| Definite |
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| Severe: prevents routine daily activities |
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| Life threatening |
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| Unlikely |
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| Possible |
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| Probable |
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| Definite |
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| Moderate |
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| Severe |
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| Pyrexia, Grade 2, Related |
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| Pyrexia, Grade 3, Related |
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| Headache, Grade 1, Related |
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| Headache, Grade 2, Related |
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| Headache, Grade 3, Related |
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| Myalgia, Grade 1, Related |
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| Myalgia, Grade 2, Related |
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| Myalgia, Grade 3, Related |
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| Chills, Grade 1, Related |
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| Chills, Grade 2, Related |
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| Chills, Grade 3, Related |
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| Nausea, Grade 1, Related |
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| Nausea, Grade 2, Related |
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| Nausea, Grade 3, Related |
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| Fatigue, Grade 1, Related |
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| Fatigue, Grade 2, Related |
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| Fatigue, Grade 3, Related |
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| Malaise, Grade 1, Related |
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| Malaise, Grade 2, Related |
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| Malaise, Grade 3, Related |
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| Injection Site Pain, Grade 2 |
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| Injection Site Pain, Grade 3 |
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| Injection Site Erythema, Grade 1 |
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| Injection Site Erythema, Grade 2 |
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| Injection Site Erythema, Grade 3 |
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| Injection Site Swelling, Grade 1 |
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| Injection Site Swelling, Grade 2 |
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| Injection Site Swelling, Grade 3 |
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| Injection Site Induration, Grade 1 |
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| Injection Site Induration, Grade 2 |
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| Injection Site Induration, Grade 3 |
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| Injection Site Pruritus, Grade 1 |
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| Injection Site Pruritus, Grade 2 |
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| Injection Site Pruritus, Grade 3 |
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| Maximum Induration |
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| Week 2 |
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| Week 4 |
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| Week 6 |
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| Week 8 |
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| Week 12 |
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| Week 2 |
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| Week 4 |
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| Week 6 |
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| Week 8 |
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| Week 12 |
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