VA-008 ACAM2000® Vaccination of Plasma Donors for the Production of VIGIV

• ClinicalTrials.gov Identifier: NCT02443623
• Recruitment Status: Completed
• First Posted: May 14, 2015
• Last Update Posted: August 18, 2021
• Sponsor: Emergent BioSolutions
• Information provided by (Responsible Party): Emergent BioSolutions

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Smallpox Vaccine Adverse Reaction	Biological: Vaccination with ACAM2000	Phase 4

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3032 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Vaccinia Vaccination (ACAM2000®) of Plasma Donors for the Production of Vaccinia Immune Globulin Intravenous (VIGIV)
• Study Start Date: September 2015
• Actual Primary Completion Date: May 2021
• Actual Study Completion Date: August 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: Single Arm Vaccinated with ACAM2000; 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.

Biological: Vaccination 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.

Outcome Measures

Primary Outcome Measures :

1. Safety as measured by the nature, date and time of onset, intensity, duration, causality, and outcome of the event post-ACAM2000 vaccination. [ Time Frame: Approximately 750 to 3000 donors will be enrolled in this study. The outcomes measures will be assessed up to 3 months post-vaccination. ]
   A final safety assessment at Day 90 post-vaccination. All related AEs (serious and non-serious) will be followed to resolution or stabilization as applicable (may extend beyond Day 90 post-vaccination).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Canada, Manitoba

Bio Products Laboratory Ltd (plasma vendor of Emergent BioSolutions)

Winnipeg, Manitoba, Canada, R3T 5Y3

Sponsors and Collaborators

Emergent BioSolutions

Investigators

• Study Director: Christine Hall, PhD; Emergent BioSolutions

More Information

• Responsible Party: Emergent BioSolutions
• ClinicalTrials.gov Identifier: NCT02443623
• Other Study ID Numbers: VA-008
• First Posted: May 14, 2015
• Last Update Posted: August 18, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Smallpox; Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs