Dose Study of ACAM2000 Smallpox Vaccine in Previously Vaccinated Adults

Study Overview
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Brief Summary
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The objective of this study is to determine the minimum dose of ACAM2000 needed to produce a cutaneous reaction in at least 90% of a population of healthy adults at least 28 years of age and previously vaccinated against smallpox.

Detailed Description
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Specifically, the objectives of this study are to: Compare the safety and tolerability of four dose levels of ACAM2000 and a standard dose of Dryvax® in healthy adults at least 28 years of age and previously vaccinated to smallpox. Safety and tolerability will be determined by examination of the local cutaneous reaction, adverse events, physical examinations, vital signs, structured interviews, and laboratory analysis. Determine the immunogenicity of four dose levels of ACAM2000 and a standard dose of Dryvax® in healthy adults at least 28 years of age by comparing: the proportion of subjects at each dose level who develop a major cutaneous reaction the proportion of subjects in each treatment group who develop neutralizing antibodies, including the fold-increase in antibody titer between Baseline and Day 30 sera; and the geometric mean vaccinia neutralizing antibody titer on Day 30. Determine the minimum dose of ACAM2000 that is calculated to produce a major cutaneous reaction in at least 90% of a population of healthy adults at least 28 years of age, with a history of smallpox vaccination.

Official Title
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The Effect of Dose on Safety, Tolerability, and Immunogenicity of ACAM2000 Smallpox Vaccine in Adults With Previous Smallpox Vaccination

Conditions
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Smallpox

Intervention / Treatment
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* Biological: ACAM2000 Smallpox Vaccine
* Biological: Vaccinia virus (calf lymph) smallpox vaccine: Dryvax®


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: have a history of previous smallpox vaccination greater than 10 years previous to the date of screening and presence of a vaccination scar. females must not be pregnant, lactating and must agree to use an effective form of birth control for the 30 days following vaccination or unable to bear children. agree to be available for the entire study and agree to comply with all requirements. exclusion criteria: children 1 year of age or younger in the household or be in close contact smallpox vaccination within ten years known or suspected Human immunodeficient virus (HIV) infection, primary immunodeficiency disorder, leukemia, lymphoma, or current radiation treatment or use of immunosuppressive or anti-neoplastic drugs or have a household member or intimate contact with the conditions listed above. renal disease current or past history of eczema or a household member or direct contact who has eczema. known allergy or past allergic reactions to latex gloves or to antibiotics which include neomycin, streptomycin, chlortetracycline, and polymyxin B known allergy or past allergic reaction to blood products. known allergy to cidofovir or sulfa-containing drugs. history of allergic phenomena following smallpox vaccination in the past, including urticaria, erythema multiforme, or Stevens-Johnson syndrome. transfusion of blood or treatment with any blood product. current or history of drug or alcohol abuse innoculation with any other live vaccine or participating in another drug or vaccine trial within 30 days of enrollment.

Ages Eligible for Study
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Minimum Age: 28 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: ACAM2000<br>Participants will receive dose 1 of the ACAM2000 smallpox vaccine | Biological: ACAM2000 Smallpox Vaccine<br>* Group 1 dose: 1.0x10-8th PFU/ml, Group 2 dose: 2.0x10-7th PFU/ml, Group 3 dose: 1.0x10-7th PFU/ml, Group 4 dose: 5.0x10-6th PFUL/ml<br>|
| Experimental: Group 2: ACAM2000<br>Participants will receive dose 2 of the ACAM2000 smallpox vaccine | Biological: ACAM2000 Smallpox Vaccine<br>* Group 1 dose: 1.0x10-8th PFU/ml, Group 2 dose: 2.0x10-7th PFU/ml, Group 3 dose: 1.0x10-7th PFU/ml, Group 4 dose: 5.0x10-6th PFUL/ml<br>|
| Experimental: Group 3: ACAM2000<br>Participants will receive dose 3 of the ACAM2000 smallpox vaccine | Biological: ACAM2000 Smallpox Vaccine<br>* Group 1 dose: 1.0x10-8th PFU/ml, Group 2 dose: 2.0x10-7th PFU/ml, Group 3 dose: 1.0x10-7th PFU/ml, Group 4 dose: 5.0x10-6th PFUL/ml<br>|
| Experimental: Group 4: ACAM2000<br>Participants will receive dose 4 of the ACAM2000 smallpox vaccine | Biological: ACAM2000 Smallpox Vaccine<br>* Group 1 dose: 1.0x10-8th PFU/ml, Group 2 dose: 2.0x10-7th PFU/ml, Group 3 dose: 1.0x10-7th PFU/ml, Group 4 dose: 5.0x10-6th PFUL/ml<br>|
| Active Comparator: Group 5: Dryvax®<br>Participants will receive dose 1 of Dryvax® smallpox vaccine. | Biological: Vaccinia virus (calf lymph) smallpox vaccine: Dryvax®<br>* Group 5 dose: 1.0x10-8th PFU/ml<br>* Other names: Dryvax®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Neutralizing Antibody Response Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine | The neutralizing antibody response titers were determined by the Plaque-Reduction Neutralization Test (PRNT50) | Day 30 post-vaccination | 
| Participants With ≥ 4-fold Increase in Plaque-Reduction Neutralization Test (PRNT50) Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine. |  | Day 30 post-vaccination | 
| Number of Participants Reporting Adverse Events of Severe Intensity Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine |  | Days 0 to 30 post-vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smallpox vaccines, Dryvax®, Orthopoxvirus, Vaccinia virus, ACAM2000