SmallpoxPhase 2NCT00050505
Expanded Dryvax Dilution Study in Previously Vaccinated Adults
A Phase 2 study testing Live vaccinia virus vaccine in people with Smallpox, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 32 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Smallpox
- What is being tested?
- Live vaccinia virus vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 927 participants
- Where
- 7 sitesUnited States
- Study dates
- Oct 2002to Dec 2003
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 32 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 32 to 70 years.
- Typical vaccinia scar or validated documentation (e.g., military record, international travel certificate) of a smallpox vaccination, but not since 1989.
- Willing to sign informed consent.
- Availability for follow-up for the planned duration of the study (at least 26 weeks after vaccination).
- Acceptable medical history by screening evaluation and brief clinical assessment.
- Negative urine or serum pregnancy test for women of childbearing potential.
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- 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).
- Negative ELISA for HIV or indeterminant Western blot or other assay confirming that the serostatus does not reflect HIV infection
- ALT < 1.5 times institutional upper limit of normal.
- Negative hepatitis B surface antigen and negative antibody to hepatitis C virus.
- Negative urine glucose by dipstick.
- 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.
- Hematocrit > 34% for females, > 38% for males; platelets > 150,000/mm3; and WBC > 2,500/mm3 and < 11,000/mm3.
Who cannot join
- Smallpox vaccination in 1990 or more recently.
- History of immunodeficiency.
- Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
- Malignancy, other than squamous cell or basal cell skin cancer.
- Active autoimmune disease.
- Use of immunosuppressive medication.
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- Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol.
- History of "illegal" injection drug use.
- Inactivated vaccine 14 days prior to vaccination
- Live attenuated vaccines within 60 days of study.
- Use of investigational agents within 30 days prior to study.
- Receipt of blood products or immunoglobulin in the past 6 months.
- Acute febrile illness on the day of vaccination.
- Pregnant or lactating women.
- Eczema of any degree or history of eczema.
- History of chronic exfoliative skin disorders/conditions.
- Any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2 x 2 cm.
- 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
- Any condition that, in the opinion of the investigator, might interfere with study objectives.
- Known allergies to any component of the vaccine (e.g., polymyxin B sulfate, dihyrostreptomycin sulfate, chlortetracycline hydrochloride, neomycin sulfate).
- Known allergies to any known component of the diluent (i.e., glycerin and phenol).
- Known allergies to any known component of VIG, i.e., thimerosal or previous allergic reaction to immunoglobulins.
- Known allergies to cidofovir or probenecid.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Maryland Baltimore
Baltimore, Maryland, 21201
Duke Health Center
Durham, North Carolina, 27704
Kaiser Permanente Vaccine Study Center
Oakland, California, 94612
University of Rochester
Rochester, New York, 14642
Saint Louis University
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305-5208
UCLA Center For Vaccine Research
Torrance, California, 90502
About this study
Official title: 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.
Read the 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.
- Conditions
- Smallpox
- Being tested
- Live vaccinia virus vaccine
- Keywords
- smallpox, Dryvax, vaccine, dilution
- Medical subject headings
- Smallpox
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Live vaccinia virus vaccineBiological
Dryvax undiluted. Cohort A receives undiluted dose of Dryvax vaccine
Live vaccinia virus vaccineBiological
Dryvax with diluent (50% glycerin and 0.25% phenol in sterile water). Cohort A-C receives diluted dose of Dryvax vaccine.
| Study group | Role | What they receive |
|---|---|---|
| Cohort C | Experimental | N=100 to 110 subjects receives 1:10 diluted dose of Dryvax vaccine on Day 0 and 1:5 revaccination dose on Day 56 Receives: Biological: Live vaccinia virus vaccine |
| Cohort B | Experimental | N=571 to 581 subjects receives 1:5 diluted dose of Dryvax vaccine on Day 0 and 1:5 revaccination dose on Day 56 Receives: Biological: Live vaccinia virus vaccine |
| Cohort A | Experimental | N=226 to 236 subjects receives undiluted dose Dryvax vaccine on Day 0 and 1:5 revaccination dose on Day 56 Receives: Biological: Live vaccinia virus vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 6 to 11 days after the first vaccination at each of the dose levels (undiluted and 1:5 and 1:10).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2002 (estimated)
- Study startOct 2002
- Study completionDec 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SmallpoxStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 927 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00050505
- Sponsor's protocol ID
- 02-007
- Status last verified
- Jul 2009
- First submitted
- 10 Dec 2002
- Last updated
- 5 Dec 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Double Blind, Randomized Dose-response Study of Dryvax Vaccine Against Smallpox in Previously Vaccinated Adults
- ClinicalTrials.gov ID
- NCT00050505
- Acronym / sponsor ID
- 02-007
- Conditions
- Smallpox
- Keywords
- smallpox, Dryvax, vaccine, dilution
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 927 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Oct 2002
- Study completion
- Dec 2003 (actual)
- First posted
- 11 Dec 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort C | Experimental | Biological: Live vaccinia virus vaccineN=100 to 110 subjects receives 1:10 diluted dose of Dryvax vaccine on Day 0 and 1:5 revaccination dose on Day 56 |
| Cohort B | Experimental | Biological: Live vaccinia virus vaccineN=571 to 581 subjects receives 1:5 diluted dose of Dryvax vaccine on Day 0 and 1:5 revaccination dose on Day 56 |
| Cohort A | Experimental | Biological: Live vaccinia virus vaccineN=226 to 236 subjects receives undiluted dose Dryvax vaccine on Day 0 and 1:5 revaccination dose on Day 56 |
Who may qualify
- Ages
- 32 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age 32 to 70 years.
- Typical vaccinia scar or validated documentation (e.g., military record, international travel certificate) of a smallpox vaccination, but not since 1989.
- Willing to sign informed consent.
- Availability for follow-up for the planned duration of the study (at least 26 weeks after vaccination).
- Acceptable medical history by screening evaluation and brief clinical assessment.
Key exclusion criteria (28 listed)
- Smallpox vaccination in 1990 or more recently.
- History of immunodeficiency.
- Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
- Malignancy, other than squamous cell or basal cell skin cancer.
- Active autoimmune disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Live vaccinia virus vaccineDryvax undiluted. Cohort A receives undiluted dose of Dryvax vaccine | Biological | Cohort A |
| Live vaccinia virus vaccineDryvax with diluent (50% glycerin and 0.25% phenol in sterile water). Cohort A-C receives diluted dose of Dryvax vaccine. | Biological | Cohort A, Cohort B, Cohort C |
Primary outcome
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Live vaccinia virus vaccine in people with Smallpox, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2014.