NCT00133575

ACAM 3000 MVA at Harvard Medical School

ACAM 3000 MVA (Acambis Modified Vaccinia Ankara) Immunization Followed by Dryvax® Vaccination of Healthy Vaccinia-Naïve Adults: A Phase I/II, Placebo-Controlled Study of the Effects of Dose and Route of Administration of MVA on Safety, Reactogenicity and Immunogenicity, Followed by Dryvax® Immunization to Assess Effects of MVA Vaccination on Dryvax® Takes

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 72 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 38 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to assess the safety of an experimental smallpox vaccine (MVA: Modified Vaccinia Ankara) and to compare the body's immune (system that fights disease) response to this vaccine. Participants will be assigned to 1 of 6 study groups. Each group will include 12 subjects, 10 will receive the modified smallpox vaccine and two will receive placebo, an inactive substance. The vaccine will be administered in 1 of 3 ways: under the skin; in the muscle; or between the muscle and the skin. Groups A and B will receive Dryvax® 6-15 months after the initial MVA vaccine; groups C, D, E, and F will receive Dryvax® 6 months after the initial MVA vaccine. Study procedures will include documenting side effects for 14 days after each vaccination, electrocardiogram (picture of the hearts activity) and blood samples. Participants will be involved in study related procedures for up to 18 months.

Detailed description

The emergence of smallpox as a potential agent of bioterrorism has heightened concern about the vulnerability of the population to infection with this agent, and has led to proposals to undertake large scale smallpox immunization of military personnel and "first responders" in the United States, including certain health care workers. A particularly promising vaccine approach to the development of an effective, yet less reactogenic vaccine to smallpox is the use of Modified Vaccinia Ankara (MVA) as a vaccine. Despite the established efficacy of smallpox vaccination, the parameters of protective immunity against smallpox infection are incompletely understood. This is a phase I/II trial to be conducted under a placebo controlled double-blind, randomized allocation of study product. The purpose of this study is to assess the safety and immunogenicity of ACAM 3000 MVA in healthy vaccinia-naïve adult subjects. Participants will include 72 healthy, male or female, from the Boston metropolitan area. Six dose regimens will be studied initially: 10\^6 or 10\^7 tissue culture infectious dose 50 (TCID50) administered intradermally and 10\^7 or 10\^8 TCID50 administered intramuscularly or subcutaneously as 2 immunizations 1 month apart. Each arm will be comprised of 12 subjects, 10 of whom will receive ACAM3000 MVA and 2 of whom will receive placebo. A subsequent vaccinia vaccination will be offered to all patients. Consenting participants in Groups A and B will receive the vaccinia (Dryvax®) inoculation between 6 and 15 months after the initial MVA / placebo vaccination. Consenting participants in groups C, D, E and F will receive the Dryvax® inoculation approximately 6 months after the initial MVA / placebo vaccination, coinciding with planned visit 13. Assessment of safety will be carried out by observation and measurement of acute clinical and laboratory evidence of reactions or toxicity; including clinical, electrocardiographic or laboratory evidence of myopericarditis. Assessment of immunogenicity will be carried out by the measurement of humoral and cell-mediated immune response to ACAM 3000 MVA and vaccinia, performed on blood samples obtained at various times prior to and after immunization over the one year period of the study. Response to vaccinia will be assessed clinically (effect on a "take") and the results will be correlated with immune responses to MVA. Subjects will be followed for reactogenicity. Clinical assessments and blood samples will be obtained sequentially for immunogenicity determinations.

Conditions

• Smallpox

Interventions

Type	Name	Description
BIOLOGICAL	MVA Smallpox Vaccine	MVA smallpox vaccine (ACAM3000 MVA) administered in two doses approximately 28 days apart in the following dose/route combination: 10\^7 or 10\^8 TCID50 intramuscularly (IM).
BIOLOGICAL	MVA Smallpox Vaccine	MVA smallpox vaccine (ACAM3000 MVA) administered in two doses approximately 28 days apart in the following dose/route combination: 10\^7 or 10\^8 TCID50 subcutaneously (SC).
OTHER	Placebo	Sterile saline (0.9%) volume of 0.5 ml intradermally in the deltoid.
OTHER	Placebo	Sterile saline (0.9%) volume of 0.5 ml subcutaneously in the deltoid.
BIOLOGICAL	MVA Smallpox Vaccine	MVA smallpox vaccine (ACAM3000 MVA) administered in two doses approximately 28 days apart in the following dose/route combination: 10\^6 or 10\^7 TCID50 intradermally (ID).
BIOLOGICAL	Live vaccinia virus vaccine	Dryvax® smallpox vaccine administered at approximately day 180, dosage 10\^8 pfu/ml.
OTHER	Placebo	Sterile saline (0.9%) volume of 0.5 ml intramuscularly in the deltoid.

Timeline

• Start date: 2005-10-01
• Primary completion: 2008-04-01
• Completion: 2008-04-01
• First posted: 2005-08-23
• Last updated: 2015-01-05
• Results posted: 2009-07-08

Locations

1 site across 1 country: United States