Expanded Dryvax Dilution Study in Previously Vaccinated Adults

December 4, 2014 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Multicenter, Double Blind, Randomized Dose-response Study of Dryvax Vaccine Against Smallpox in Previously Vaccinated Adults

The purpose of this study is to determine the safety and effect of diluting smallpox vaccine, making a larger number of doses in case smallpox is released into the environment. A total of up to 927 healthy adults between the ages of 32 and 70 years who were already vaccinated against smallpox (but not since 1989) will volunteer for this study for up to 34 weeks and receive different strengths of vaccine. Some subjects may participate for longer if they choose to be revaccinated because the first vaccination does not take. The vaccine will be given by making small cuts in the skin and putting the vaccine into these cuts. After the screening visit, volunteers will be followed through study visits and follow up phone calls. Blood will be collected during some study visits to look at the immune system (body system that fights infection) response.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The purposes of this multi-center, double blind randomized dose response study are: to evaluate the safety of undiluted Dryvax and Dryvax diluted at 1:5 and 1:10 in adults between the ages of 32 and 70 years who were previously vaccinated but not since 1989 and to define, with very high precision (+/-3%), the proportion of individuals who respond with a "take" 6 to 11 days after vaccination with undiluted Dryvax vaccine and Dryvax diluted at 1:5. A "take" is defined as the formation of a lesion at the site of vaccination that is consistent with the description of a successful vaccination described in the IB Secondary study objectives include defining with good precision (+/- 10%), the proportion of individuals who respond with a "take" 6 to 11 days after vaccination with a 1:10 dilution of Dryvax vaccine and exploring correlations between "takes"/ no-"take" and immune responses in all vaccine groups (antibody responses in all volunteers; and assays of cell-mediated immunity in a convenience sample consisting of 15 volunteers enrolled at each site (total N = 105) randomly distributed across the vaccine groups). Immunogenicity assays will include neutralizing antibody to vaccinia, vaccinia binding antibody, ELISPOT for gamma interferon [Assays of cell-mediated immunity will be performed only on a convenience sample consisting of 15 volunteers enrolled at each site (total N = 105)] and intracellular cytokine production. Primary safety endpoints include safety data regarding the three doses of vaccine in previously vaccinated subjects as assessed by adverse events reported by the subjects and/or investigators and changes observed during the scheduled clinic visits. Specific attention will be paid to the following: local reactogenicity at the site of injection: pain, tenderness, erythema, induration, regional lymphadenopathy, limitation of limb movement; systemic symptoms: fever, myalgia, fatigue, and headache; anaphylaxis, and hypersensitivity reactions; other reactions: dermatologic, neurologic, gastrointestinal (nausea/vomiting, diarrhea). The primary efficacy endpoint for this trial will be the proportion of vaccinees demonstrating a "take" 6 to 11 days after the first vaccination at each of the dose levels (undiluted and 1:5 and 1:10). Secondary endpoints are: immune responses as assessed by vaccinia neutralizing antibody measured on all subjects and binding antibody to vaccinia on all subjects and the size of the lesions observed in all subjects compared across the dilution groups. Tertiary endpoints of 15 volunteers at each site randomly distributed across the vaccine groups are cellular immune responses as assessed by: ELISPOT for gamma interferon in response to vaccinia antigens and intracellular cytokine production.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
927

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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
    • California
      • Oakland, California, United States, 94612
        • Kaiser Permanente Vaccine Study Center
      • Stanford, California, United States, 94305-5208
        • Stanford University
      • Torrance, California, United States, 90502
        • UCLA Center for Vaccine Research
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Baltimore
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Saint Louis University
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester
    • North Carolina
      • Durham, North Carolina, United States, 27704
        • Duke Health Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

32 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 32 to 70 years.
  2. Typical vaccinia scar or validated documentation (e.g., military record, international travel certificate) of a smallpox vaccination, but not since 1989.
  3. Willing to sign informed consent.
  4. Availability for follow-up for the planned duration of the study (at least 26 weeks after vaccination).
  5. Acceptable medical history by screening evaluation and brief clinical assessment.
  6. Negative urine or serum pregnancy test for women of childbearing potential.
  7. If the subject is female and of childbearing potential, she must use an acceptable contraception and not become pregnant within 56 days post vaccination. (Acceptable contraception includes implants, injectables, combined oral contraceptives, effective intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner).
  8. Negative ELISA for HIV or indeterminant Western blot or other assay confirming that the serostatus does not reflect HIV infection
  9. ALT < 1.5 times institutional upper limit of normal.
  10. Negative hepatitis B surface antigen and negative antibody to hepatitis C virus.
  11. Negative urine glucose by dipstick.
  12. Adequate renal function defined as a serum creatinine less than or equal to 1.5 mg/dL; urine protein < 100 mg/dL or trace or negative proteinuria by dipstick; and a calculated creatinine clearance > 55 mL/min based on the formulas in the manual of procedures.
  13. Hematocrit > 34% for females, > 38% for males; platelets > 150,000/mm3; and WBC > 2,500/mm3 and < 11,000/mm3.

Exclusion Criteria:

  1. Smallpox vaccination in 1990 or more recently.
  2. History of immunodeficiency.
  3. Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
  4. Malignancy, other than squamous cell or basal cell skin cancer.
  5. Active autoimmune disease.
  6. Use of immunosuppressive medication.
  7. Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol.
  8. History of "illegal" injection drug use.
  9. Inactivated vaccine 14 days prior to vaccination
  10. Live attenuated vaccines within 60 days of study.
  11. Use of investigational agents within 30 days prior to study.
  12. Receipt of blood products or immunoglobulin in the past 6 months.
  13. Acute febrile illness on the day of vaccination.
  14. Pregnant or lactating women.
  15. Eczema of any degree or history of eczema.
  16. History of chronic exfoliative skin disorders/conditions.
  17. Any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2 x 2 cm.

  18. Household contacts/sexual contacts with, or frequent and/or prolonged exposure to, any of the following:

    • Pregnant women
    • Children < 12 months of age
    • People with or history of eczema
    • People with chronic exfoliative skin disorders/conditions or any acute skin disorders of large magnitude. e.g., laceration requiring sutures, burn greater than 2 x 2 cm
    • People with immunodeficiency disease or use of immunosuppressive medications
  19. Any condition that, in the opinion of the investigator, might interfere with study objectives.
  20. Known allergies to any component of the vaccine (e.g., polymyxin B sulfate, dihyrostreptomycin sulfate, chlortetracycline hydrochloride, neomycin sulfate).
  21. Known allergies to any known component of the diluent (i.e., glycerin and phenol).
  22. Known allergies to any known component of VIG, i.e., thimerosal or previous allergic reaction to immunoglobulins.
  23. Known allergies to cidofovir or probenecid.

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: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort C
N=100 to 110 subjects receives 1:10 diluted dose of Dryvax vaccine on Day 0 and 1:5 revaccination dose on Day 56
Biological: Live vaccinia virus vaccine
Dryvax undiluted. Cohort A receives undiluted dose of Dryvax vaccine
Biological: Live vaccinia virus vaccine
Dryvax with diluent (50% glycerin and 0.25% phenol in sterile water). Cohort A-C receives diluted dose of Dryvax vaccine.
Experimental: Cohort B
N=571 to 581 subjects receives 1:5 diluted dose of Dryvax vaccine on Day 0 and 1:5 revaccination dose on Day 56
Biological: Live vaccinia virus vaccine
Dryvax undiluted. Cohort A receives undiluted dose of Dryvax vaccine
Biological: Live vaccinia virus vaccine
Dryvax with diluent (50% glycerin and 0.25% phenol in sterile water). Cohort A-C receives diluted dose of Dryvax vaccine.
Experimental: Cohort A
N=226 to 236 subjects receives undiluted dose Dryvax vaccine on Day 0 and 1:5 revaccination dose on Day 56
Biological: Live vaccinia virus vaccine
Dryvax undiluted. Cohort A receives undiluted dose of Dryvax vaccine
Biological: Live vaccinia virus vaccine
Dryvax with diluent (50% glycerin and 0.25% phenol in sterile water). Cohort A-C receives diluted dose of Dryvax vaccine.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Proportion of vaccinees demonstrating a "take" 6 to 11 days after the first vaccination at each of the dose levels (undiluted and 1:5 and 1:10).
Time Frame: 6 to 11 days after the first vaccination at each of the dose levels (undiluted and 1:5 and 1:10).
6 to 11 days after the first vaccination at each of the dose levels (undiluted and 1:5 and 1:10).

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Allergy and Infectious Diseases (NIAID)

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2002

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2003

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 10, 2002

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2002

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 11, 2002

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 5, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 4, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 02-007

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