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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00053495
First received: January 30, 2003
Last updated: May 7, 2012
Last verified: May 2012
  Purpose

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


Condition Intervention Phase
Smallpox
Biological: Vaccinia virus: ACAM2000 smallpox vaccine
Biological: vaccinia virus (calf lymph): Dryvax
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Effect of Dose On Safety, Tolerability, and Immunogenicity of ACAM2000 Smallpox Vaccine in Adults Without Previous Smallpox Vaccination

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Number of Participants Reporting Adverse Events of Severe Intensity Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine [ Time Frame: Days 0 to 30 post-vaccination ] [ Designated as safety issue: No ]
    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.

  • Neutralizing Antibody Response Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine. [ Time Frame: Day 30 post-vaccination ] [ Designated as safety issue: No ]
  • Participants With ≥ 4-fold Increase in Plaque-Reduction Neutralization Test (PRNT50) Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine. [ Time Frame: Day 30 post-vaccination ] [ Designated as safety issue: No ]

Enrollment: 353
Study Start Date: January 2003
Study Completion Date: November 2003
Primary Completion Date: June 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1: ACAM2000 Dose 1
Participants will receive a single dose of ACAM2000 smallpox vaccine, 1.0x10-8th plaque-forming units/mL on Day 0.
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
Experimental: Group 2: ACAM2000 Dose 2
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
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
Experimental: Group 3: ACAM2000 Dose 3
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
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
Experimental: Group 4: ACAM2000 Dose 4
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
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
Active Comparator: Group 5: Dryvax® Vaccine
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
Group 5 dose: 1.0x10-8th PFU/ml
Other Name: Dryvax®

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

Ages Eligible for Study:   18 Years to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00053495

Locations
United States, Florida
Orlando Clinical Research Center
Orlando, Florida, United States, 32806
United States, Kansas
PRA International
Lenexa, Kansas, United States, 66219
United States, Missouri
Bio-Kinetic Clinical Applications
Springfield, Missouri, United States, 65802
United States, Rhode Island
Memorial Hospital of Rhode IslandDivision of Infectious Diseases
Pawtucket, Rhode Island, United States, 02860
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Medical Director Sanofi Pasteur Inc
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00053495     History of Changes
Other Study ID Numbers: H-400-005
Study First Received: January 30, 2003
Results First Received: January 3, 2011
Last Updated: May 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Smallpox

Additional relevant MeSH terms:
Smallpox
Poxviridae Infections
DNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on August 28, 2014