A Non-inferiority Trial to Compare MVA-BN® Smallpox Vaccine to ACAM2000®
Primary Purpose
18-42 Year Old Healthy Vaccinia-naïve Subjects
Status
Completed
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
MVA BN®
ACAM2000®
Sponsored by
About this trial
This is an interventional prevention trial for 18-42 Year Old Healthy Vaccinia-naïve Subjects
Eligibility Criteria
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:
- Total bilirubin greater than 1.5 x Upper Limit Normal (ULN)
- Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) greater than 1.5 x ULN
- Alkaline Phosphatase (Alk Phos) greater than 1.5 x ULN
- 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:
- Pregnant women
- Children <12 months of age
- People with eczema or a history of eczema
- People with active AD or history of AD
- People with chronic exfoliative skin disorders/conditions
- People with active Varicella zoster, Herpes zoster, impetigo, uncontrolled acne, Darier's disease or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn with areas greater than 2×2 cm
- People with active or recent immunodeficiency disease or use of immunosuppressive medications, for example: have or take medication for HIV, AIDS, leukemia, lymphoma, or chronic liver problem, have or take medication for Crohn's disease, lupus, arthritis, or other immune disease; have had radiation or X-ray treatment (not routine X-rays) within the last 3 months; have ever had a bone-marrow or organ transplant (or take medication for that ); or have another problem that requires steroids, prednisone or a cancer drug for treatment
- People having had eye surgery within the last 4 weeks
- 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
Sites / Locations
- Brian Allgood Army Community Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Group 1
Group 2
Arm Description
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).
A single vaccination of ACAM2000® will be administered at Day 0.
Outcomes
Primary Outcome Measures
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.
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).
Secondary Outcome Measures
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)
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)
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)
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).
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.
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.
Relationship to Vaccine of Any Serious Adverse Event (SAE)
Presentation of SAEs by relationship to study vaccine
Intensity of Any Serious Adverse Event (SAE)
Presentation of SAEs by intensity
Incidence of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis, i.e. Adverse Events of Special Interest (AESIs)
In this clinical trial, an AESI was defined as any cardiac sign or symptom developed since the first vaccination, any ECG changes determined to be clinically significant, or any cardiac enzyme results of Troponin I ≥ 2 x ULN.
Related Grade >=3 Adverse Events
Incidence of any Grade 3 or 4 adverse events (AEs) possibly, probably, or definitely related to the vaccine. Pooled solicited (general only) and unsolicited AEs.
Relationship to Vaccine of Any Non-serious AEs
Presentation of non-serious AEs by relationship to study vaccine
Intensity of Any Non-serious AEs
Presentation of non-serious AEs by intensity
Solicited General AEs
Occurrence, intensity and relationship of solicited general AEs (body temperature [fever], headache, myalgia [muscle pain], chills, nausea, fatigue, malaise)
Incidence of Lymphadenopathy
Incidence of events of Lymphadenopathy. Pooled solicited and unsolicited events.
Solicited Local AEs: Intensity
Incidence of solicited local AEs (pain, redness [erythema], swelling, induration, itching [pruritus])
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.
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.
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.
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'.
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'.
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.
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.
Full Information
NCT ID
NCT01913353
First Posted
July 26, 2013
Last Updated
November 18, 2019
Sponsor
Bavarian Nordic
Collaborators
US Army Medical Research Institute of Infectious Diseases
1. Study Identification
Unique Protocol Identification Number
NCT01913353
Brief Title
A Non-inferiority Trial to Compare MVA-BN® Smallpox Vaccine to ACAM2000®
Official Title
A Randomized, Open-label Phase III Non-inferiority Trial to Compare Indicators of Efficacy for MVA-BN® Smallpox Vaccine to ACAM2000® in 18-42 Year Old Healthy Vaccinia-naïve Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
March 2015 (Actual)
Primary Completion Date
March 2017 (Actual)
Study Completion Date
August 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bavarian Nordic
Collaborators
US Army Medical Research Institute of Infectious Diseases
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To demonstrate the efficacy of MVA-BN® in terms of vaccinia-specific Plaque Reduction Neutralization Test (PRNT) antibody response and by showing that vaccination prior to administration of ACAM2000® results in an attenuated take.
Detailed Description
To demonstrate the efficacy of MVA-BN® by assessing non-inferiority of MVA-BN® compared to ACAM2000® in terms of vaccinia-specific Plaque Reduction Neutralization Test (PRNT) antibody response at the Peak Visits (Day 42 for Group 1 and Day 28 for Group 2) and by showing that vaccination with MVA-BN® prior to administration of ACAM2000® results in an attenuation of take.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
18-42 Year Old Healthy Vaccinia-naïve Subjects
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
440 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
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).
Arm Title
Group 2
Arm Type
Active Comparator
Arm Description
A single vaccination of ACAM2000® will be administered at Day 0.
Intervention Type
Biological
Intervention Name(s)
MVA BN®
Other Intervention Name(s)
IMVAMUNE, IMVANEX
Intervention Description
0.5 ml MVA BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection
Intervention Type
Biological
Intervention Name(s)
ACAM2000®
Intervention Description
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 Outcome Measure Information:
Title
Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT) at the Peak Visits
Description
GMT based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of 1.
Time Frame
Day 42 for Group 1 and Day 28 for Group 2
Title
Maximum Lesion Area (MLA) in mm2 After Scarification With ACAM2000®
Description
The MLA was defined as the maximum of two measurements: the lesion area measured on Day 6-8 (after scarification) or the lesion area measured on Day 13-15 (after scarification). This was measured using the SilhouetteConnect camera system, and confirmed by the Independent Take Review Committee (ITRC).
Time Frame
Day 6-8, 13-15 after 3rd Vaccination for Group 1 and Day 6-8, 13-15 after 1st vaccination for Group 2
Secondary Outcome Measure Information:
Title
Investigator-measured Maximum Lesion Diameter (MLD) in mm After Scarification With ACAM2000
Description
The MLD was defined as the largest major diameter measured across the lesion on Day 6-8 (after scarification) or Day 13-15 (after scarification)
Time Frame
Day 6-8 and Day 13-15 after ACAM2000 scarification
Title
Investigator-measured Lesion Diameter in mm at Day 6-8 After Scarification With ACAM2000
Description
The lesion diameter at Day 6-8 was defined as the major lesion diameter measured on Day 6-8 (after scarification)
Time Frame
Day 6-8 after ACAM2000 scarification
Title
Investigator-measured Lesion Diameter in mm at Day 13-15 After Scarification With ACAM2000
Description
The lesion diameter at Day 13-15 was defined as the major lesion diameter measured on Day 13-15 (after scarification)
Time Frame
Day 13-15 after ACAM2000 scarification
Title
Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC)
Description
Take was assessed as either full, partial, or absent take by the ITRC based on Day 6-8 evaluations following ACAM2000 vaccination using subject profiles that contained supportive data up to Day 14 following ACAM2000 vaccination (in accordance with the ITRC Charter).
Time Frame
Day 6-8 visit following ACAM2000 vaccination
Title
Lesion Area in mm2 at Day 6-8 After Scarification With ACAM2000
Description
Lesion area was measured by the Investigator using the SilhouetteConnect camera system and confirmed by the blinded ITRC.
Time Frame
Day 6-8 after ACAM2000 scarification
Title
Lesion Area in mm2 at Day 13-15 After Scarification With ACAM2000
Description
Lesion area was measured by the Investigator using the SilhouetteConnect camera system and confirmed by the blinded ITRC.
Time Frame
Day 13-15 after ACAM2000 scarification
Title
Relationship to Vaccine of Any Serious Adverse Event (SAE)
Description
Presentation of SAEs by relationship to study vaccine
Time Frame
Within 38 weeks for Group 1 and 30 weeks for Group 2
Title
Intensity of Any Serious Adverse Event (SAE)
Description
Presentation of SAEs by intensity
Time Frame
Within 38 weeks for Group 1 and 30 weeks for Group 2
Title
Incidence of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis, i.e. Adverse Events of Special Interest (AESIs)
Description
In this clinical trial, an AESI was defined as any cardiac sign or symptom developed since the first vaccination, any ECG changes determined to be clinically significant, or any cardiac enzyme results of Troponin I ≥ 2 x ULN.
Time Frame
Within 38 weeks for Group 1 and 30 weeks for Group 2
Title
Related Grade >=3 Adverse Events
Description
Incidence of any Grade 3 or 4 adverse events (AEs) possibly, probably, or definitely related to the vaccine. Pooled solicited (general only) and unsolicited AEs.
Time Frame
within 29 days after vaccination
Title
Relationship to Vaccine of Any Non-serious AEs
Description
Presentation of non-serious AEs by relationship to study vaccine
Time Frame
within 29 days after vaccination
Title
Intensity of Any Non-serious AEs
Description
Presentation of non-serious AEs by intensity
Time Frame
within 29 days after vaccination
Title
Solicited General AEs
Description
Occurrence, intensity and relationship of solicited general AEs (body temperature [fever], headache, myalgia [muscle pain], chills, nausea, fatigue, malaise)
Time Frame
within 15 days after vaccination
Title
Incidence of Lymphadenopathy
Description
Incidence of events of Lymphadenopathy. Pooled solicited and unsolicited events.
Time Frame
within 29 days after vaccination
Title
Solicited Local AEs: Intensity
Description
Incidence of solicited local AEs (pain, redness [erythema], swelling, induration, itching [pruritus])
Time Frame
within 15 days after vaccination
Title
Major Lesion Size, Major Erythema, and Major Induration Diameter
Description
Daily measurement of major lesion size, major erythema, and major induration diameter (mm) based on physical appearance of vaccination site as documented in the memory aid. If the shape of the lesion, erythema [excludes lymphangitis], and induration observed was not round but rather asymmetrical, then the largest [or major] cross-sectional measurement was recorded.
Time Frame
Within 15 days after scarification with ACAM2000
Title
GMTs at the Peak Visits and Individual Peak Measured by Vaccinia-specific ELISA
Description
Peak Visit was defined as Day 42 for Group 1 and Day 28 for Group 2. Individual Peak was the maximum titer per subject from Visit 1 to Visit 7 (Week 8) in Group 1 and maximum titer from Visit 1 to Visit 6 (Week 8) in Group 2.
Titers below the detection limit are included with a value of 1.
Time Frame
within 8 weeks (for both groups)
Title
GMTs at the Individual Peak Measured by Vaccinia-specific PRNT
Description
Individual Peak was the maximum titer per subject from Visit 1 to Visit 7 (Week 8) in Group 1 and maximum titer from Visit 1 to Visit 6 (Week 8) in Group 2.
Titers below the detection limit are included with a value of 1.
Time Frame
within 8 weeks (for both groups)
Title
GMTs as Measured by Vaccinia-specific ELISA
Description
GMT based on vaccinia-specific ELISA. Titers below the detection limit are included with a value of '1'.
Time Frame
within 12 weeks
Title
GMTs as Measured by Vaccinia-specific PRNT
Description
GMT based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of '1'.
Time Frame
within 12 weeks
Title
PRNT Seroconversion Rates at Peak Visits
Description
Seroconversion rate based on PRNT. Seroconversion is defined as the appearance of antibody titers "greater than or equal" detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Time Frame
Group 1 at Week 6; Group 2 at Week 4
Title
ELISA Seroconversion Rates at Peak Visits
Description
Seroconversion rate based on ELISA. Seroconversion is defined as the appearance of antibody titers "greater than or equal" detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Time Frame
Group 1 at Week 6; Group 2 at Week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
42 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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:
Total bilirubin greater than 1.5 x Upper Limit Normal (ULN)
Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) greater than 1.5 x ULN
Alkaline Phosphatase (Alk Phos) greater than 1.5 x ULN
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:
Pregnant women
Children <12 months of age
People with eczema or a history of eczema
People with active AD or history of AD
People with chronic exfoliative skin disorders/conditions
People with active Varicella zoster, Herpes zoster, impetigo, uncontrolled acne, Darier's disease or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn with areas greater than 2×2 cm
People with active or recent immunodeficiency disease or use of immunosuppressive medications, for example: have or take medication for HIV, AIDS, leukemia, lymphoma, or chronic liver problem, have or take medication for Crohn's disease, lupus, arthritis, or other immune disease; have had radiation or X-ray treatment (not routine X-rays) within the last 3 months; have ever had a bone-marrow or organ transplant (or take medication for that ); or have another problem that requires steroids, prednisone or a cancer drug for treatment
People having had eye surgery within the last 4 weeks
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Phillip R Pittman, MD, MPH
Organizational Affiliation
US Army Medical Research Institute of Infectious Diseases
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brian Allgood Army Community Hospital
City
Seoul
Country
Korea, Republic of
12. IPD Sharing Statement
Citations:
PubMed Identifier
31722150
Citation
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.
Results Reference
derived
Learn more about this trial
A Non-inferiority Trial to Compare MVA-BN® Smallpox Vaccine to ACAM2000®
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