Effect of Dose, Safety, Tolerability of a New Smallpox Vaccine in Adults Without Previous Smallpox Vaccination

Study Overview
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Brief Summary
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The purpose of this study is to examine the safety and the effectiveness of a new vaccine for the prevention of the disease, smallpox.

Detailed Description
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The objective of this study is to 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 18-29 years of age and naïve to smallpox vaccine. 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 18-29 years of age and naïve to smallpox vaccine. 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 18-29 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 18-29 years of age and naïve to smallpox vaccine.

Official Title
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The Effect of Dose On Safety, Tolerability, and Immunogenicity of ACAM2000 Smallpox Vaccine in Adults Without Previous Smallpox Vaccination

Conditions
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Smallpox

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 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: military service prior to 1989. history of previous smallpox vaccination. children 1 year of age or younger in the household or be in close contact smallpox vaccination within ten years known or suspected human immunodeficiency 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 inoculation 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: 18 Years
Maximum Age: 29 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 Dose 1<br>Participants will receive a single dose of ACAM2000 smallpox vaccine, 1.0x10-8th plaque-forming units (PFU)/mL on Day 0. | Biological: Vaccinia virus: ACAM2000 smallpox vaccine<br>* Group 1 dose: 1.0x10-8th PFU/ml Group 2 dose: 2.0x10-8th PFU/ml Group 3 dose: 1.0x10-7th PFU/ml Group 4 dose: 5.0x10-6th PFU/ml<br>|
| Experimental: Group 2: ACAM2000 Dose 2<br>Participants will receive a single dose of ACAM2000 smallpox vaccine, 2.0x10-8th plaque-forming units/mL on Day 0. | Biological: Vaccinia virus: ACAM2000 smallpox vaccine<br>* Group 1 dose: 1.0x10-8th PFU/ml Group 2 dose: 2.0x10-8th PFU/ml Group 3 dose: 1.0x10-7th PFU/ml Group 4 dose: 5.0x10-6th PFU/ml<br>|
| Experimental: Group 3: ACAM2000 Dose 3<br>Participants will receive a single dose of ACAM2000 smallpox vaccine, 1.0x10-7th plaque-forming units/mL on Day 0 | Biological: Vaccinia virus: ACAM2000 smallpox vaccine<br>* Group 1 dose: 1.0x10-8th PFU/ml Group 2 dose: 2.0x10-8th PFU/ml Group 3 dose: 1.0x10-7th PFU/ml Group 4 dose: 5.0x10-6th PFU/ml<br>|
| Experimental: Group 4: ACAM2000 Dose 4<br>Participants received a single dose of ACAM2000 smallpox vaccine, 5.0x10-6th plaque-forming units/mL on Day 0 | Biological: Vaccinia virus: ACAM2000 smallpox vaccine<br>* Group 1 dose: 1.0x10-8th PFU/ml Group 2 dose: 2.0x10-8th PFU/ml Group 3 dose: 1.0x10-7th PFU/ml Group 4 dose: 5.0x10-6th PFU/ml<br>|
| Active Comparator: Group 5: Dryvax® Vaccine<br>Participants will receive a single dose of Dryvax® smallpox vaccine, 1.0x10-8th plaque-forming units/mL on Day 0 | Biological: vaccinia virus (calf lymph): 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 |
| --- | --- | --- |
| Number of Participants Reporting Adverse Events of Severe Intensity Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine | The severity of each reported adverse event was classified by the investigator according to the following definitions. None - no symptom; Mild - awareness of sign or symptoms, but easily tolerated; Moderate - discomfort enough to cause interference with usual activity; and Severe - incapacitating with inability to work or perform usual activity. | Days 0 to 30 post-vaccination | 
| Neutralizing Antibody Response Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine. |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smallpox