Smallpox Vaccine Adverse Reaction
Conditions
Brief summary
Objectives: * To vaccinate plasma donors with the ACAM2000 smallpox vaccine thereby inducing an immune response resulting in high anti-vaccinia antibody titers. The collection of donor plasma will be used in the manufacturing of Vaccinia Immune Globulin Intravenous (VIGIV). * To ensure the safety of plasma donors vaccinated with ACAM2000 through the implementation of risk factor screening procedures and the collection of post-vaccination safety data.
Detailed description
This protocol is being conducted to vaccinate plasma donors with the ACAM2000 smallpox vaccine thereby inducing an immune response resulting in high anti-vaccinia antibody titers. The collection of donor plasma will be used in the manufacturing of Vaccinia Immune Globulin Intravenous (VIGIV). The objective of this protocol is to ensure the safety of plasma donors vaccinated with ACAM2000 through the implementation of risk factor screening procedures and the collection of post-vaccination safety data. Participants will be followed for the duration of the study, an expected average of 90 days as described below in the planned study assessments. Screening \[complete within 14 days before Baseline (Day 0)\]: * Informed consent obtained from prospective donors * Post-consent information including medical history, smallpox vaccination history, current medications, detailed demographics, BMI, physical exam, vital signs, and assessment for pericarditis/myocarditis symptoms, blood samples will be collected and a baseline EKG (if applicable). Baseline (Day 0) prior to vaccination: -Physical exam and vital signs, urine pregnancy test for all female subjects of child-bearing potential, current medications, assessment for pericarditis/myocarditis. Baseline (Day 0) vaccination and post-vaccination: -Vaccination with ACAM2000, vaccination site inspection 30 post-vaccination, unanticipated problems, all adverse events including all cardiovascular adverse events (symptoms and signs), concomitant medications. Post-vaccination Day 3 (±1): -Assessment for pericarditis/myocarditis, vaccination site inspection, unanticipated problems, unexpected and serious adverse reactions or complications post-vaccination, all adverse events including all cardiovascular adverse events (symptoms and signs). Post-vaccination Day 7 (±1): -Assessment of pericarditis/myocarditis symptoms, urine pregnancy test, vaccination site inspection, unanticipated problems, all adverse events including all cardiovascular adverse events (symptoms and signs), concomitant medications. Post-vaccination Day 12 (±2), 21 (±3), and 28 (±3): -Assessment of pericarditis/myocarditis symptoms, urine pregnancy test, vaccination site inspection, unanticipated problems, all adverse events including all cardiovascular adverse events (symptoms and signs), concomitant medications. End of study post-vaccination Day 35 (±3) or Early Withdrawal: Vital signs, assessment of pericarditis/myocarditis symptoms, urine pregnancy test, vaccination site inspection, unanticipated problems, all adverse events including all cardiovascular adverse events (symptoms and signs), concomitant medications. Final Safety Assessment Day 90 (±3): Assessment for pericarditis/myocarditis, unanticipated problems, unexpected and serious adverse reactions or complications post-vaccination, all adverse events including all cardiovascular adverse events (symptoms and signs).
Interventions
BIOLOGICALVaccination with ACAM2000
In this study (VA-008), healthy adult male and female volunteers who meet the requirements for source plasma donors and study entry criteria will be vaccinated with the ACAM2000 smallpox vaccine for collection of plasma to be used in the manufacture of VIGIV. There are possible risks associated with ACAM2000 vaccination. To ensure the safety of plasma donors, risk factor screening procedures and the collection of post-vaccination safety data will be assessed throughout the study.
Sponsors
Emergent BioSolutions
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed written informed consent. * Age 18 to 65. * Normal and healthy (immune competent) as determined by medical history, physical exam, vital signs and clinical laboratory tests during the screening period. * If all lab results for quantitative IgA immunoglobulin level are lower than 15% below normal range, the subject may not proceed further in the screening process. * Subject must meet all required subject suitability criteria that pertain to normal source plasma donors. * Negative HIV serology during screening period. * Subject must have been previously immunized for smallpox, at ≥3 years prior to commencement of screening assessments, and vaccination history must be confirmed by oral or written history and the presence of a visible pathognomonic smallpox vaccination scar.
Exclusion criteria
* History of severe related adverse event(s) from previous participation in VA-001 or VA-006 trials or to any smallpox vaccination. * The subject, or a household contact or other close/intimate contact of the subject has ANY of the following: * Eczema, history of eczema, exfoliative skin conditions, wounds, burns, or other skin conditions at the investigator's discretion. * A history of immunodeficiency. * Currently or has recently received radiotherapy or chemotherapy, adrenocorticotropic hormone (ACTH), corticosteroids, or immunosuppressive drugs. * Eye disease treated with topical steroids. * Known or suspected disorders of immunoglobulin synthesis. * Leukemia, lymphomas of any type, melanoma, or other malignant neoplasms affecting the bone marrow or lymphatic systems. * Has been diagnosed with cancer and who will be undergoing chemotherapy or radiation therapy during the vaccination healing time. * Is a transplant recipient (except for corneal transplant). * Is pregnant, planning pregnancy or breast feeding (female subjects of childbearing potential must have negative pregnancy test prior to vaccination). Women of child-bearing potential (WOCBP) are temporarily excluded due to COVID. * Household or other close/intimate contact(s) under the age of 12 months. * History of allergies to phenol, any of the antibiotics listed in the vaccine content, or any other component of ACAM2000 or its diluents. * Subjects with kidney disease (except kidney stones). * Subjects with abnormal EKG at screening (if applicable). To mitigate the risk of enrolling at risk subjects and potentially jeopardizing subject safety an EKG will be performed prior to vaccination with ACAM2000 smallpox vaccine in all potential subjects ≥50 years old and for all potential subjects \<50 with two cardiac risk factors as listed immediately below including; severely or morbidly obese or higher obesity classification (BMI ≥36); high blood pressure; high blood cholesterol; diabetes or high blood sugar; a first degree relative who had a heart condition before the age of 50; and current tobacco smokers. * Subject has three or more of the following risk factors: * Severely or morbidly obese or higher obesity classification (BMI ≥36) * High blood pressure diagnosed by a doctor * High blood cholesterol diagnosed by a doctor * Diabetes or high blood sugar diagnosed by a doctor * A first degree relative (for example, mother, father, brother, sister) who had a heart condition before the age of 50 * Currently smokes tobacco (cigarettes) * Cardiovascular disease or heart condition diagnosed by a doctor at any time in the past, with or without symptoms, including: * Arrhythmia * Syncope related to cardiac disease * Previous myocardial infarction * Angina * Coronary artery disease * Congestive heart failure * Cardiomyopathy * Stroke or transient ischemic attack * Myocarditis * Pericarditis * Chest pain or shortness of breath with activity (such as climbing stairs), peripheral edema, heart palpitations, dry cough, irregular heartbeat, excessive fatigue, unexplained syncope * Other heart conditions being treated by a physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Vaccinated Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs) | Adverse event data was collected from vaccinated participants through Day 90. | Number of subjects with AEs including SAEs up to 90 days after vaccination. |
| Number of Vaccinated Participants With Related Adverse Events | Adverse event data was collected from vaccinated participants through Day 90. | Number of subjects with related AEs up to 90 days after vaccination. |
| Number of Vaccinated Participants With Serious Adverse Events (SAEs) | Adverse event data was collected from vaccinated participants through Day 90. | Number of subjects with SAEs up to 90 days after vaccination. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Vaccinated With ACAM2000 Healthy adult male and female volunteers who met the requirements for source plasma donation and study entry criteria were vaccinated with the ACAM2000 smallpox vaccine for collection of plasma used in the manufacture of VIGIV. | 3,032 |
| Total | 3,032 |
Baseline characteristics
| Characteristic | Single Arm Vaccinated With ACAM2000 |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 18 Participants |
| Age, Categorical Between 18 and 65 years | 3013 Participants |
| BMI | 30.4 kg/m^2 STANDARD_DEVIATION 6.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 626 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2325 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 81 Participants |
| Height | 174.3 cm STANDARD_DEVIATION 9.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 64 Participants |
| Race (NIH/OMB) Asian | 25 Participants |
| Race (NIH/OMB) Black or African American | 744 Participants |
| Race (NIH/OMB) More than one race | 27 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 13 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 36 Participants |
| Race (NIH/OMB) White | 2123 Participants |
| Region of Enrollment United States | 3032 participants |
| Sex: Female, Male Female | 765 Participants |
| Sex: Female, Male Male | 2267 Participants |
| Weight | 92.5 kg STANDARD_DEVIATION 20.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 3,032 | 0 / 0 |
| other Total, other adverse events | 1,413 / 3,032 | 1,190 / 3,032 |
| serious Total, serious adverse events | 25 / 3,032 | 0 / 0 |
Outcome results
Primary
Number of Vaccinated Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs)
Number of subjects with AEs including SAEs up to 90 days after vaccination.
Time frame: Adverse event data was collected from vaccinated participants through Day 90.
Population: The safety population consisted of 3032 participants who were vaccinated, including 208 participants who were vaccinated twice (n= 208 includes two participants who were inadvertently vaccinated twice and were included twice in demography and all participant counts).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm Vaccinated With ACAM2000 | Number of Vaccinated Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs) | 1420 Participants |
Primary
Number of Vaccinated Participants With Related Adverse Events
Number of subjects with related AEs up to 90 days after vaccination.
Time frame: Adverse event data was collected from vaccinated participants through Day 90.
Population: The safety population consisted of 3032 participants who were vaccinated, including 208 participants who were vaccinated twice (n= 208 includes two participants who were inadvertently vaccinated twice and were included twice in demography and all participant counts).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm Vaccinated With ACAM2000 | Number of Vaccinated Participants With Related Adverse Events | 1190 Participants |
Primary
Number of Vaccinated Participants With Serious Adverse Events (SAEs)
Number of subjects with SAEs up to 90 days after vaccination.
Time frame: Adverse event data was collected from vaccinated participants through Day 90.
Population: The safety population consisted of 3032 participants who were vaccinated, including 208 participants who were vaccinated twice (n= 208 includes two participants who were inadvertently vaccinated twice and were included twice in demography and all participant counts).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm Vaccinated With ACAM2000 | Number of Vaccinated Participants With Serious Adverse Events (SAEs) | 25 Participants |