Clinical trial NCT02443623: VA-008 ACAM2000® Vaccination of Plasma Donors for the Production of VIGIV
Official title: Vaccinia Vaccination (ACAM2000®) of Plasma Donors for the Production of Vaccinia Immune Globulin Intravenous (VIGIV)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Smallpox Vaccine Adverse Reaction
Lead sponsor: Emergent BioSolutions
Sponsor class: INDUSTRY
First posted: 2015-05-14
Enrollment: 3032
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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).

Eligibility criteria: 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

Primary outcomes:
measure: Number of Vaccinated Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs)
timeFrame: Adverse event data was collected from vaccinated participants through Day 90.
measure: Number of Vaccinated Participants With Related Adverse Events
timeFrame: Adverse event data was collected from vaccinated participants through Day 90.
measure: Number of Vaccinated Participants With Serious Adverse Events (SAEs)
timeFrame: Adverse event data was collected from vaccinated participants through Day 90.
Secondary outcomes:
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: Bio Products Laboratory Ltd (plasma vendor of Emergent BioSolutions)
state: Manitoba
Study officials:
affiliation: Emergent BioSolutions
name: Christine Hall, PhD
role: STUDY_DIRECTOR
References: