NCT00879762

High Dose IMVAMUNE® in Vaccinia-Naive Individuals

Comparison of Safety and Immunogenicity of a High Dose (5 x 10^8 TCID50) and a Standard Dose (1 x 10^8 TCID50) of IMVAMUNE® in Healthy Vaccinia-Naive Individuals

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 91 (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 research is to compare the ability of a new investigational smallpox vaccine called IMVAMUNE® to produce a strong immune response against smallpox disease if given as one single, higher dose compared with two lower doses given one month apart. Another purpose of the study is to see how quickly someone might be protected against smallpox. Volunteers will be vaccinia-naïve adults age 18 and older (born after 1971) divided into 2 groups. Volunteers in Group A will receive a high dose of vaccine given in 2 shots on day 0 followed by a placebo (inactive substance) shot on day 28. Group B will receive the standard dose of vaccine and placebo given in 2 shots on day 0 followed by a standard dose shot on Day 28. Study participation will include 10 planned study visits over approximately 7 months.

Detailed description

Despite the fact that the World Health Organization (WHO) officially declared smallpox to be eradicated, a new threat exists due to the potential use of variola virus as an agent for biological warfare and/or bio-terrorism. As a consequence, there is an urgent need for a safe and efficacious vaccine to protect the public against smallpox. To date, the majority of clinical studies with Modified Vaccinia Ankara (MVA) have studied a prime-boost vaccination regimen, with a dose of up to 1×10\^8 tissue culture infectious dose 50 (TCID50) of MVA administered on Days 0 and 28. While this vaccination regimen induces a robust immune response that is protective in a variety of animal models and is appropriate for a pre-smallpox release scenario, in the event of a confirmed release of smallpox, a more rapid vaccination regimen that provides a protective immune response would be desirable. Ideally, at least short-term protection could be obtained with a single dose of vaccine. While a single dose of MVA at 1×10\^8 TCID50, does induce an immune response in the majority of recipients, it is possible that a higher dose of MVA could provide a more rapid and/or stronger immune response relative to a single, standard 1×10\^8 TCID50 dose of MVA. The goal of this study is to examine the kinetics and magnitude of the immune response of a single high dose of MVA (5×10\^8 TCID50) relative to both a single and prime/boost regimen using the standard doses (1×10\^8 TCID50) of MVA. This study will complement a current, ongoing study, DMID Protocol 06-0012, which is examining the immune response to compressed prime/boost dosing regimens of MVA administered at (1×10\^8 TCID50). Upon the completion of these studies, clinical data will be generated which will inform policy makers about different options for post-event utilization of available smallpox vaccines. The study is designed as a randomized, non-placebo controlled, double blinded study containing two arms: Group A (N=45) will receive a single high dose of IMVAMUNE® (5x10\^8 TCID50, consisting of two 0.5 mL injections) vaccine on Day 0 and a single saline placebo dose (single 0.5 mL injection) on Day 28 to match the two dose regimen of Group B. Group B (N=45) will receive a standard two dose regimen of IMVAMUNE® (1x10\^8 TCID50) vaccine on Day 0 (consisting of 0.5 mL injection of vaccine and 0.5 mL injection of saline placebo) and Day 28 (single 0.5 mL injection of vaccine). Safety will be measured by assessment of adverse events for 28 days following the last vaccination (56 days following the initial vaccination for those subjects that fail to receive the second dose) and for serious adverse events at six months post the final vaccination, and reactogenicity to the vaccines for 15 days following each vaccination. Immunogenicity testing will include antibody testing \[enzyme linked immunosorbent assay (ELISA) and plaque reduction neutralizing antibody titers (PRNT)\] and cellular immune responses \[(INF-gamma enzyme linked immunospot (ELISPOT)\] following each vaccination and at six months post the final vaccination. In addition, ELISA responses, using MVA VR-1508 as the target antigen and PRNT using vaccinia WR (Western Reserve) as the target antigen will be explored. Participants will include 90 healthy, vaccinia-naïve adults, aged 18 and older (born after 1971). Study duration will be approximately 13 months (7 months/subject).

Conditions

• Smallpox

Interventions

Type	Name	Description
BIOLOGICAL	MVA Smallpox Vaccine	IMVAMUNE® Vaccinia Vaccine, undiluted, delivered by subcutaneous route on Day 0 at high dose 5×10\^8 TCID50 (5×10\^8 TCID50 per 1.0 mL dose - administered as 2 x 0.5 mL.
OTHER	Placebo	0.5 mL injection of saline placebo administered with vaccine on Day 0 (Group B) or single saline placebo dose (single 0.5 mL injection) on Day 28 (Group A).

Timeline

• Start date: 2009-05-29
• Primary completion: 2011-03-09
• Completion: 2011-03-09
• First posted: 2009-04-10
• Last updated: 2025-06-13
• Results posted: 2025-06-13

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study