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

March 14, 2024 updated by: Emergent BioSolutions

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

353

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Orlando, Florida, United States, 32806
        • Orlando Clinical Research Center
    • Kansas
      • Lenexa, Kansas, United States, 66219
        • PRA International
    • Missouri
      • Springfield, Missouri, United States, 65802
        • Bio-Kinetic Clinical Applications
    • Rhode Island
      • Pawtucket, Rhode Island, United States, 02860
        • Memorial Hospital of Rhode IslandDivision of Infectious Diseases

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 29 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1: ACAM2000 Dose 1
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
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 Names:
  • Dryvax®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Day 30 post-vaccination
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
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.
Time Frame: Day 30 post-vaccination
Day 30 post-vaccination

Other Outcome Measures

Outcome Measure
Time Frame
Number of Participants With Treatment-Emergent Rash Events Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.
Time Frame: Days 0 to 30 post-vaccination
Days 0 to 30 post-vaccination
Clinical Chemistry Parameters (Aspartate Aminotransaminase and Alanine Aminotransferase) at Baseline and Day 15 Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine
Time Frame: Days 0 (baseline) and 15 post-vaccination
Days 0 (baseline) and 15 post-vaccination
Clinical Chemistry Parameters (Creatinine and Glucose) at Baseline and Day 15 Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine
Time Frame: Days 0 (baseline) and 15 post-vaccination
Days 0 (baseline) and 15 post-vaccination
Selected Hematology Parameters (Hematocrit, Lymphocyte, and Eosinophil) at Baseline and on Day 15 in Participants Vaccinated With ACAM2000 or Dryvax® Smallpox Vaccine.
Time Frame: Days 0 (baseline) and 15 post-vaccination
Days 0 (baseline) and 15 post-vaccination
Selected Hematology Parameters (Red Blood Count and Platelets) at Baseline and on Day 15 in Participants Vaccinated With ACAM2000 or Dryvax® Smallpox Vaccine.
Time Frame: Days 0 (baseline) and 15 post-vaccination
Days 0 (baseline) and 15 post-vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emergent BioSolutions

Investigators

  • Study Director: Medical Director, Emergent BioSolutions

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2003

Primary Completion (Actual)

June 1, 2003

Study Completion (Actual)

November 1, 2003

Study Registration Dates

First Submitted

January 30, 2003

First Submitted That Met QC Criteria

January 30, 2003

First Posted (Estimated)

January 31, 2003

Study Record Updates

Last Update Posted (Actual)

March 18, 2024

Last Update Submitted That Met QC Criteria

March 14, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-400-005

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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