Safety, Reactogenicity and Immunogenicity of MVA in Hematopoietic Stem Cell Transplant (HSCT) Subjects
Condition: Variola Major (Smallpox)
MeSH terms: Smallpox
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to compare how the body's immune system reacts to a vaccine
      against smallpox infection, called Modified Vaccinia Ankara (MVA) and to evaluate the safety
      of this vaccine. Study participants will include 24 adults, ages 18-60 years, who have
      undergone a stem cell transplant more than 2 years ago. Study procedures will include a
      physical exam, blood samples, heart activity assessments, and urine samples. Participants
      will be assigned to 1 of 2 possible study vaccine groups. The participants will receive 1 of
      2 possible vaccine doses or placebo (substance containing no medication) 28 days apart.
      Participants will make at least 8 visits to the clinic during the course of the study;
      additional visits may be needed if the participant experiences side effects from the vaccine.
      Participants may be involved in study related procedures for about 6 months.
    

Detailed description: 
      In the event of a smallpox outbreak, or threat of one, mass immunization of all vulnerable
      individuals would take place. This would include persons with immunodeficiency as seen post
      Hematopoietic Stem Cell Transplant (HSCT). The current Food and Drug Administration (FDA)
      approved smallpox vaccine (Dryvax®) is a live replicating virus (vaccinia) and is
      contraindicated in both immunocompromised persons and those in close physical contact with
      them. The Modified Vaccinia Ankara (MVA), specifically IMVAMUNE® has been developed as a
      safer, less reactogenic vaccine against smallpox. Study participants will include 24 male or
      female participants, from 18 to 60 years of age. This study assesses the safety,
      reactogenicity and immunogenicity of 2 doses of MVA-BN (IMVAMUNE®) given to persons who have
      undergone an HSCT more than 2 years prior to study participation. There are 2 arms in the
      study, each receiving 2 doses 28 days apart of either 1 x 10^7 or 1 x 10^8 tissue culture
      infectious dose 50 (TCID50). Each arm will be comprised of 12 subjects, 10 of whom will
      receive IMVAMUNE® and 2 of whom will receive placebo under a double blind, randomized
      allocation. Subjects will be followed for safety and reactogenicity. Clinical assessments
      will be performed and blood samples will be obtained sequentially for safety and
      immunogenicity determinations. All subjects will complete a memory aid for 15 days after each
      vaccination to record oral temperature and note the occurrence of solicited and unsolicited
      adverse events as well as any medication use. Adverse events will be collected for 56 days
      after each vaccination. Serious adverse events and concomitant medications will be collected
      throughout the entire study period. Study staff will assess subjects clinically at days 14
      and 28 after each vaccination and on days 42, 56, 84, and 180. Hematology and blood chemistry
      studies including hemoglobin, white blood cell and platelet counts and kidney and liver
      function tests will be obtained. Electrocardiogram and Troponin I or T will be obtained prior
      to first vaccination and on days 14 and 28 after each immunization and at day 180. Clinical
      laboratory assays will be conducted in the clinical laboratory at both the Brigham and
      Women's Hospital or the Dana Farber Cancer Institute. The primary objective of this study is
      to determine the safety and reactogenicity of MVA in persons who have undergone allogeneic
      HSCT more than 2 years prior to study participation. The secondary objective of this study is
      to determine the immunogenicity of MVA in persons who have undergone HSCT more than 2 years
      prior to study participation. Immunogenicity will be determined by humoral immune responses
      and cell mediated immune responses.
    

Intervention name(s): Placebo; MVA-BN
Intervention type(s): Drug; Biological
Intervention description(s): Sterile saline (0.9%).; The smallpox vaccine is a liquid frozen solution formulated to contain 0.605 mg Tris and 4.090 mg sodium chloride (NaCl) per 0.5 mL dose. The concentration of the virus will be 1 X 10^8 tissue culture infectious dose 50 (TCID 50) per 0.5 mL dose and may be diluted in a solution of 0.9% saline prior to vaccination. Smallpox vaccine administered in 2 doses approximately 28 days apart in one of the following doses: 1X10^7 or 1X10^8 TCID 50.
Intervention MeSH terms: Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Variola major, smallpox, vaccine, hematopoietic stem cell transplant