NCT00914732

Lyophilized IMVAMUNE® (1x10^8 TCID50) Versus Liquid IMVAMUNE® (1x10^8 TCID50) Administered Subcutaneously and a Lower Dose Liquid IMVAMUNE® (2x10^7 TCID50) Administered Intradermally

Comparison of the Safety and Immunogenicity of Lyophilized IMVAMUNE® (1x10^8 TCID50) Versus Liquid Formulation IMVAMUNE® (1x10^8 TCID50) Administered by the Subcutaneous Route and a Lower Dose Liquid Formulation IMVAMUNE® (2x10^7 TCID50) Administered by the Intradermal Route in Healthy Vaccinia-Naïve Individuals

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 523 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 38 Years
• Healthy volunteers: Accepted

Summary

Due to recent concern of biowarfare and bioterrorism, the US government is making efforts to improve its ability to protect citizens against the smallpox virus. This study will evaluate safety of IMVAMUNE®, an investigational smallpox vaccine, and its ability to stimulate the immune system (the body's defense system). Two vaccine preparations have the same name but one is a liquid and one is a powder that has liquid added just before it is given. The vaccine that comes as a liquid will be injected (given as a shot) just under the skin (subcutaneously) or injected between the layers of the skin (intradermally). The powder formulation is only injected just under the skin. Approximately 495 adults, age 18 older born after 1971, which have not had smallpox vaccine before, may participate in the study for about 7 months.

Detailed description

Smallpox was declared officially eradicated by the World Health Assembly in 1980. 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. Following the events of September 11, 2001 the Division of Microbiology and Infectious Diseases/National Institute of Allergy and Infectious Diseases contracted for the advanced development of IMVAMUNE®. Initially, a lyophilized formulation was manufactured, which was reconstituted 'at the bedside' prior to administration in clinical and non-clinical settings. Due in part to the potential requirement for mass vaccinations coupled with the increased manufacturing time and other constrains associated with lyophilization, it was decided to transition to a liquid product formulation. Therefore, after 2005, clinical and non-clinical efforts have focused largely on the liquid formulation, though non-clinical studies with the lyophilized formulation continued. Presently, due to the potential need to be able to stockpile Modified Vaccinia Ankara (MVA) for an extended period of time, there is renewed interest in the lyophilized formulation. The purpose of this study is to compare the safety and immunogenicity of lyophilized IMVAMUNE® \[1x10\^8 tissue culture infectious dose 50 (TCID50)\] versus liquid formulation IMVAMUNE® (1x10\^8 TCID50) administered by the subcutaneous (SC) route and a lower dose liquid formulation IMVAMUNE® (2x10\^7 TCID50) administered by the intradermal (ID) route in healthy vaccinia-naïve individuals. This study is designed as a randomized, non-placebo controlled, partially-blinded study (liquid versus lyophilized formulation by the SC route Group B versus A). The study staff is unblinded to Group C. The study will contain 3 arms: Group A \[Number (N)=165\] will receive a 2 dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL per dose) lyophilized formulation by the SC route on Day 0 and 28. Group B (N=165) will receive a 2 dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL per dose) liquid formulation by the SC route on Day 0 and 28. Group C (N=165) will receive a 2 dose regimen of IMVAMUNE® (2x10\^7 TCID50/0.1 mL per dose) liquid formulation by the ID route on Day 0 and 28. Safety will be measured by assessment of solicited local and systemic reactions within 15 days after each vaccination (Day 0-14), unsolicited adverse events for 28 days following the second vaccination (56 days following the initial vaccination for those subjects that fail to receive the second vaccination), and serious adverse events through six months post the final vaccination. Immunogenicity testing will include assessment of vaccinia-specific plaque reduction neutralizing antibody titers (PRNT) and enzyme linked immunosorbent assay (ELISA) mean geometric titers (GMT) based on individual peak titers. For each subject, the peak PRNT or ELISA will be defined as the largest titer among all available measurements post second vaccination.

Conditions

• Smallpox

Interventions

Type	Name	Description
BIOLOGICAL	MVA Smallpox Vaccine	Vaccinia vaccine liquid formulation delivered by subcutaneous (SC) route at 1x10\^8 TCID50 per 0.5 mL dose on Days 0 and 28.
BIOLOGICAL	MVA Smallpox Vaccine	Vaccinia vaccine liquid formulation delivered at lower dose \[2x10\^7 tissue culture infectious dose 50 (TCID50) per 0.1 mL dose\] by intradermal (ID) route on Days 0 and 28.
BIOLOGICAL	MVA Smallpox Vaccine	Vaccinia vaccine lyophilized formulation delivered by subcutaneous (SC) route at 1x10\^8 TCID50 per 0.5 mL dose on Days 0 and 28.

Timeline

• Start date: 2010-02-01
• Primary completion: 2011-04-01
• Completion: 2011-04-01
• First posted: 2009-06-05
• Last updated: 2021-02-03
• Results posted: 2021-01-12

Locations

8 sites across 1 country: United States