Phase 2 Study of Safety, Tolerability, and Immunogenicity of Three Dose Levels of ACAM3000 Smallpox Vaccine

• ClinicalTrials.gov Identifier: NCT00466245
• Recruitment Status: Completed
• First Posted: April 27, 2007
• Last Update Posted: January 22, 2014
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

A phase 2 study to assess the MVA smallpox vaccine in previously vaccinated and vaccine- naive subjects at three dose levels.

Condition or disease	Intervention/treatment	Phase
Smallpox	Drug: MVA Smallpox vaccine; Drug: Placebo	Phase 2

Detailed Description:

This study will be a randomized, double-blind, placebo-controlled out-patient study conducted in multiple centers in the United States (US). Up to 700 healthy male and female adult subjects 18 to 55 years of age (inclusive), who have been previously vaccinated or subjects who are naïve to smallpox vaccine will be enrolled. Subjects will be randomized to 1 of 8 treatment groups with 100 (or 50 placebo) subjects per group in which they will receive either ACAM3000 MVA Smallpox Vaccine (1 of 3 dose levels) or placebo on Study Days 0 and 28. All personnel associated with the trial will be blinded as to treatment, with the exception of the study pharmacist who prepares the treatment for administration to each subject. There are 2 control groups in this study. A comparison of adverse events and other safety assessments between placebo and ACAM3000 MVA Smallpox Vaccine will be performed. In addition to serving as a control for safety, the previously vaccinated subjects receiving placebo will serve as a control for antibody and T-cell responses in persons with preexisting immunity who receive ACAM3000 MVA Smallpox Vaccine. Safety, tolerability, and immunogenicity data for 110 subjects undergoing primary immunization with graded doses of ACAM3000 MVA Smallpox Vaccine will be available following completion of Acambis protocol H-249-001, an ongoing phase I clinical trial. The doses levels in this study may be changed following the availability of results from protocol H-249-001. Statistical analysis will focus on comparisons among the dose levels of ACAM3000 MVA Smallpox Vaccine and comparisons of ACAM3000 MVA Smallpox Vaccine to placebo, as appropriate. A separate analysis will be performed for previously vaccinated and naïve subjects. Descriptive statistics will be used to compare demographic and baseline clinical data between stratum.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 590 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2 Study Assessing Safety, Tolerability, Immunogenicity of Three Dose Levels of ACAM3000 Modified Vaccinia Ankara Smallpox Vaccine in Adults With and Without Previous Smallpox Vaccination
• Study Start Date: July 2005
• Actual Primary Completion Date: June 2006
• Actual Study Completion Date: June 2006

Arms and Interventions

Arm	Intervention/treatment
Experimental: A; Previously vaccinated for smallpox, 1x10-8 dose	Drug: MVA Smallpox vaccine; Two 0.5mL subcutaneous injections, separated by 28 days
Experimental: B; Smallpox vaccine naive, 1x10-8 dose	Drug: MVA Smallpox vaccine; Two 0.5mL subcutaneous injections, separated by 28 days
Experimental: C; Previous smallpox vaccination, 1x10-7 dose	Drug: MVA Smallpox vaccine; Two 0.5mL subcutaneous injections, separated by 28 days
Experimental: D; Smallpox vaccine naive, 1x10-7 dose	Drug: MVA Smallpox vaccine; Two 0.5mL subcutaneous injections, separated by 28 days
Experimental: E; Previous smallpox vaccination, 1x10-6 dose	Drug: MVA Smallpox vaccine; Two 0.5mL subcutaneous injections, separated by 28 days
Experimental: F; Smallpox vaccine naive, 1x10-6 dose	Drug: MVA Smallpox vaccine; Two 0.5mL subcutaneous injections, separated by 28 days
Experimental: G; Previous smallpox vaccination, placebo dose	Drug: Placebo; Two 0.5mL subcutaneous injections, separated by 28 days
Experimental: H; Smallpox vaccine naive, placebo dose	Drug: Placebo; Two 0.5mL subcutaneous injections, separated by 28 days

Outcome Measures

Primary Outcome Measures :

1. Safety [ Time Frame: Study Completion ]

Secondary Outcome Measures :

1. Immunogenicity [ Time Frame: Study Completion ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• subjects must be in good general health, checked on toxicity grading table.
• for previously vaccinated subjects- must be between the ages of 33 and 55 with a previous vaccine more than 10 years ago.
• for vaccine naive subjects- must be between the ages of 18 and 32, and have never been vaccinated for smallpox.
• Female subjects must not be pregnant or lactating.

Exclusion Criteria:

• Subjects who participated in a "first responder" program.
• any history of immunodeficiency.
• any autoimmune disease
• any history of cardiac disease
• any diagnosed risk factors for ischemic coronary disease
• any history of heart palpitations or abnormalities in cardiac rhythm.
• any current or history of eczema of any description.
• Known allergy to MVA or any of its components, including eggs or egg products.
• morbid obesity

Contacts and Locations

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Monitor; Sanofi Pasteur Inc

More Information

Additional Information:

Related Info 

Related Info 

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00466245
• Obsolete Identifiers: NCT00170651
• Other Study ID Numbers: H-249-002
• First Posted: April 27, 2007
• Last Update Posted: January 22, 2014
• Last Verified: January 2014

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

MVA Vaccine

Additional relevant MeSH terms:

Smallpox; Poxviridae Infections; DNA Virus Infections; Virus Diseases