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

Smallpox Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00053495
• Other study ID #: H-400-005
• Status: Completed
• Phase: Phase 2
• Start date: January 2003
• Est. completion date: November 2003

Study information

• Verified date: March 2024
• Source: Emergent BioSolutions
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 353
• Est. completion date: November 2003
• Est. primary completion date: June 2003
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 29 Years

Eligibility

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.

Related Conditions & MeSH terms

• Smallpox

Intervention

Biological:
• Vaccinia virus: ACAM2000 smallpox vaccine
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
• vaccinia virus (calf lymph): Dryvax
Group 5 dose: 1.0x10-8th PFU/ml

Locations

Country	Name	City	State
United States	PRA International	Lenexa	Kansas
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Memorial Hospital of Rhode IslandDivision of Infectious Diseases	Pawtucket	Rhode Island
United States	Bio-Kinetic Clinical Applications	Springfield	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Emergent BioSolutions

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment-Emergent Rash Events Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.		Days 0 to 30 post-vaccination
Other	Clinical Chemistry Parameters (Aspartate Aminotransaminase and Alanine Aminotransferase) at Baseline and Day 15 Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine		Days 0 (baseline) and 15 post-vaccination
Other	Clinical Chemistry Parameters (Creatinine and Glucose) at Baseline and Day 15 Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine		Days 0 (baseline) and 15 post-vaccination
Other	Selected Hematology Parameters (Hematocrit, Lymphocyte, and Eosinophil) at Baseline and on Day 15 in Participants Vaccinated With ACAM2000 or Dryvax® Smallpox Vaccine.		Days 0 (baseline) and 15 post-vaccination
Other	Selected Hematology Parameters (Red Blood Count and Platelets) at Baseline and on Day 15 in Participants Vaccinated With ACAM2000 or Dryvax® Smallpox Vaccine.		Days 0 (baseline) and 15 post-vaccination
Primary	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
Primary	Neutralizing Antibody Response Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.		Day 30 post-vaccination
Primary	Participants With = 4-fold Increase in Plaque-Reduction Neutralization Test (PRNT50) Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.		Day 30 post-vaccination