Clinical trial NCT00053495: Effect of Dose, Safety, Tolerability of a New Smallpox Vaccine in Adults Without Previous Smallpox Vaccination
Official title: The Effect of Dose On Safety, Tolerability, and Immunogenicity of ACAM2000 Smallpox Vaccine in Adults Without Previous Smallpox Vaccination
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Smallpox
Keywords: Smallpox
Lead sponsor: Emergent BioSolutions
Sponsor class: INDUSTRY
First posted: 2003-01-31
Enrollment: 353
Sex: ALL
Minimum age (years): 18
Maximum age (years): 29
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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:

1. 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.
2. 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:

   1. the proportion of subjects at each dose level who develop a major cutaneous reaction;
   2. 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.
3. 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Reporting Adverse Events of Severe Intensity Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine
timeFrame: Days 0 to 30 post-vaccination
measure: Neutralizing Antibody Response Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.
timeFrame: Day 30 post-vaccination
measure: Participants With ≥ 4-fold Increase in Plaque-Reduction Neutralization Test (PRNT50) Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.
timeFrame: Day 30 post-vaccination
Secondary outcomes:
Other outcomes:
measure: Number of Participants With Treatment-Emergent Rash Events Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.
timeFrame: Days 0 to 30 post-vaccination
measure: Clinical Chemistry Parameters (Aspartate Aminotransaminase and Alanine Aminotransferase) at Baseline and Day 15 Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine
timeFrame: Days 0 (baseline) and 15 post-vaccination
measure: Clinical Chemistry Parameters (Creatinine and Glucose) at Baseline and Day 15 Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine
timeFrame: Days 0 (baseline) and 15 post-vaccination
measure: Selected Hematology Parameters (Hematocrit, Lymphocyte, and Eosinophil) at Baseline and on Day 15 in Participants Vaccinated With ACAM2000 or Dryvax® Smallpox Vaccine.
timeFrame: Days 0 (baseline) and 15 post-vaccination
measure: Selected Hematology Parameters (Red Blood Count and Platelets) at Baseline and on Day 15 in Participants Vaccinated With ACAM2000 or Dryvax® Smallpox Vaccine.
timeFrame: Days 0 (baseline) and 15 post-vaccination
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Lenexa
country: United States
facility: PRA International
state: Kansas
city: Springfield
country: United States
facility: Bio-Kinetic Clinical Applications
state: Missouri
city: Pawtucket
country: United States
facility: Memorial Hospital of Rhode IslandDivision of Infectious Diseases
state: Rhode Island
Study officials:
affiliation: Emergent BioSolutions
name: Medical Director
role: STUDY_DIRECTOR
References: