Variola Major (Smallpox) Clinical Trial
Official title:
MVA-BN (IMVAMUNE®) Immunization in Persons Who Have Undergone Prior Hematopoietic Stem Cell Transplant (HSCT): A Phase I, Placebo-Controlled Study of the Safety, Reactogenicity and Immunogenicity of MVA Immunization
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.
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. ;
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00879762 -
High Dose IMVAMUNE® in Vaccinia-Naive Individuals
|
Phase 2 |