SmallpoxPhase 1NCT00082446
Combination Study With MVA BN and Dryvax
A Phase 1 study testing Live vaccinia virus vaccine and MVA Smallpox Vaccine in people with Smallpox, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
The overall goals of this study are to expand the available data on the safety and immunogenicity of MVA-BN in vaccinia-naive adults and to determine the optimum dose of MVA-BN to induce immune responses and attenuate Dryvax take reactions. Participants will include 90 healthy volunteers, ages 18-32 years. Read more about this study
- Who is it for?
- Ages 18 to 32 yearsHealthy volunteers can take part
- Conditions the study is for
- Smallpox
- What is being tested?
- Live vaccinia virus vaccine and MVA Smallpox Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 91 participants
- Where
- 1 siteUnited States
- Study dates
- May 2004to Aug 2007
- Phase
- Phase 1
- 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 18 to 32 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Ages 18-32.
- Never received smallpox vaccination.
- Read, signed and dated informed consent document.
- Availability for follow-up for the planned duration of the study two years after first immunization.
- Acceptable medical history by screening evaluation and limited physical examination.
- For women, negative serum pregnancy test at screening and negative urine or serum pregnancy test within 24 hours prior to vaccination.
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- If the volunteer is female and of child bearing potential, she agrees to use acceptable contraception, and not become pregnant for at least 56 days after the last vaccination. A woman is considered of child bearing potential unless post-menopausal or surgically sterilized. [Acceptable contraception methods are restricted to effective intrauterine devices (IUDs) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination.] Women who are not sexually active must agree to use one of the acceptable contraception methods if they are of childbearing potential.
- Negative ELISA for HIV.
- ALT<1.25 times institutional upper limit of normal.
- Negative hepatitis B surface antigen and negative antibody to hepatitis C virus.
- Negative urine glucose by dipstick or urinalysis.
- Adequate renal function defined as a serum creatinine less than or equal to 1.4mg/dL for males and less than or equal to 1.2mg/dL for females; urine protein < 30 mg/dL or none or trace proteinuria (by urinalysis or dipstick); and a calculated creatine clearance greater than or equal to 80 mL/min. based on the following formulas:
- Males [(140-age in years) X weight in kg]/(72 X serum creatinine)
- Females 0.85X[(140-age in years) X weight in kg]/(72 X serum creatinine)
- ECG without clinical significance (e.g., all kinds of atrioventricular or intraventricular conditions or blocks such as complete left or right bundle branch block, AV-node block, QTc or PR prolongation, premature atrial contractions or other atrial arrhythmia, sustained ventricular arrhythmia, or 2 premature ventricular contractions (PVC) in a row, or ST elevation consistent with ischemia)
- CBC: Hemoglobin >11g/dl; White blood cells greater than 2,500 and less than 11,000/cubic mm; Platelets greater than or equal to 140,000/cubic mm.
Who cannot join
- History of immunodeficiency.
- Typical vaccinia scar.
- Known or suspected history of smallpox vaccination.
- Military service prior to 1989 or after January 2003.
- Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
- Malignancy, including squamous cell skin cancer or basal cell skin cancer at vaccination site or history of skin cancer at the vaccination site.
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- Active autoimmune disease. Persons with vitiligo or thyroid disease on thyroid replacement are not excluded.
- History of keloid formation.
- History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor.
- History of an immediate family member (father, mother, brother or sister) who has had onset of ischemic heart disease before age 50 years.
- Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's Risk Assessment Tool for Estimating Your 10-Year Risk of Having a Heart Attack, located at the following URL: http://hin.nhlbi.nih.gov/atpiii/calculator.asp. NOTE: This criterion applies only to volunteers 20 years of age and older.
- Abnormal troponin I.
- Use of immunosuppressive medication. Corticosteroid nasal sprays are permissible. Persons who have used topical steroid can be enrolled after their therapy is completed.
- Medical or psychiatric condition or occupational responsibilities that preclude volunteer compliance with the protocol.
- Any history of "illegal" injection drug use.
- Receipt of inactivated vaccine 14 days prior to vaccination.
- Receipt of live attenuated vaccines within 30 days of vaccination.
- Use of experimental agents within 30 days prior to vaccination.
- Receipt of blood products or immunoglobulin in the 6 months prior to vaccination.
- Acute febrile illness (greater than or equal to 100.5 degrees F) on the day of vaccination.
- Pregnant or lactating women.
- Eczema of any degree or history of eczema.
- People with atopic dermatitis, Varicella zoster, chronic exfoliative skin disorders/conditions or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2x2 cm.
- Household contacts/sexual contacts with, or occupational exposure to (other than minimal contact), any of the following: Pregnant women; Children <12 months of age; People with or history of eczema; People with atopic dermatitis, Varicella zoster, chronic exfoliative skin disorders/conditions or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2x2 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 or any component of MVA or MVA-BN vaccine (e.g., tris(hydroxymethl)-amino methane, sodium chloride, sucrose, dextran, L-Glutamic acid monopotassium, chicken embryo fibroblast proteins, gentamycin).
- Known allergy to egg or aminoglycoside.
- Known allergies to any component of the Dryvax® vaccine (e.g. polymyxin B sulfate, dihydrostreptomycin sulfate, chlorotetracycline hydrochloride, neomycin sulfate).
- Known allergies to any known component of the Dryvax® diluent (i.e. glycerin and phenol).
- Known allergies to any known components of vaccinia immunoglobulin (VIG), i.e. thimerosal or previous allergic reaction to immunoglobulins.
- Known allergies to cidofovir or probenecid.
- Study personnel.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of MVA-BN in a Dose Response Regimen Followed by Administration of Dryvax in Healthy Adult Volunteers
The overall goals of this study are to expand the available data on the safety and immunogenicity of MVA-BN in vaccinia-naive adults and to determine the optimum dose of MVA-BN to induce immune responses and attenuate Dryvax take reactions. Participants will include 90 healthy volunteers, ages 18-32 years. Participants will be randomly assigned to 1 of 6 study groups (groups A-F). Participants will be involved in study related procedures for up to 2 years. During this time, volunteers will return periodically for blood draws to check immune responses.
Read the detailed description
The primary goal of this phase I trial is to expand the available data on the safety and immunogenicity of MVA-BN in vaccinia-naïve adults. The secondary goals of this vaccine trial are: to determine the optimum dose of MVA-BN, given twice, to induce an immune response and attenuate Dryvax® take reactions; and to compare the ability of 2 routes of administration of MVA-BN, subcutaneous and intramuscular, to induce an immune response at the highest tested dose. A total of 90 healthy adult volunteers ages 18-32 will participate in this study. The volunteers will be randomly assigned to 1 of 6 groups to be immunized with: MVA-BN (subcutaneously) at 1 of 3 dose levels and Dryvax® (per scarification); placebo (subcutaneously) and Dryvax® (per scarification); MVA-BN (subcutaneously) at the highest dose level and placebo scarification; or MVA-BN (intramuscularly) at the highest dose level and Dryvax® (per scarification). The study will last about 30 months. Each volunteer's participation will last 6 months for all treatment groups. Subjects randomized to treatment groups D and E will have follow-up for 2 years. During this time, volunteers will return periodically for blood draws to check immune responses. Subjects will require visits for dressing changes as needed post-Dryvax vaccination. Variables to be investigated include: adverse events and side effects to the vaccines, and immunogenicity testing including antibody and cellular responses to the vaccines.
- Conditions
- Smallpox
- Being tested
- Live vaccinia virus vaccine, MVA Smallpox Vaccine, Placebo
- Keywords
- Smallpox, vaccine
- 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®: 0.25 mL of vaccine will be administered by the standard route of scarification using a bifurcated needle on day 112 for Groups A, B, C, D and F.
MVA Smallpox VaccineBiological
Imvamune/MVA-BN 1x10^8 will be administered intramuscularly to Group F on day 0 and day 28.
MVA Smallpox VaccineBiological
Imvamune/MVA-BN Groups A, B C and E will be administered subcutaneously: 2x10^7, 5x10^7, 1x10^8, 1x10^8, respectively, on days 0 and day 28.
PlaceboOther
Group E will receive sterile saline placebo for injection via scarification on day 112.
PlaceboOther
Group D will receive sterile saline placebo for injection subcutaneously on day 0 and day 28.
| Study group | Role | What they receive |
|---|---|---|
| E | Experimental | Subject will receive an SC dose of MVA 1x10^8 on day 0 and day 28. On day 112 subjects will receive a dose of placebo by scarification. Receives: Biological: MVA Smallpox Vaccine; Other: Placebo |
| D | Active comparator | Subject will receive a SC dose of placebo on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification. Receives: Biological: Live vaccinia virus vaccine; Other: Placebo |
| C | Experimental | Subject will receive a SC dose of MVA 1x10^8 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification. Receives: Biological: Live vaccinia virus vaccine; Biological: MVA Smallpox Vaccine |
| B | Experimental | Subjects will receive a SC dose of MVA 5x10^7 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification. Receives: Biological: Live vaccinia virus vaccine; Biological: MVA Smallpox Vaccine |
| A | Experimental | Subjects will receive a SC dose of MVA 2x10^7 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification. Receives: Biological: Live vaccinia virus vaccine; Biological: MVA Smallpox Vaccine |
| F | Experimental | Subject will receive an IM dose of MVA 1x10^8 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification. Receives: Biological: Live vaccinia virus vaccine; Biological: MVA Smallpox Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events and side effects to the vaccines.
Measured: Reactogenicity will be evaluated for a 2-week period post-vaccination at each time point and for the duration of study.
Secondary outcomes (1)
Immunogenicity testing of antibody and cellular responses to the vaccines.
Measured: Visit days 0, 14, 28, 42, 56, 112, 140, 182, 365, and 730.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2004 (estimated)
- Study startMay 2004
- Primary completionAug 2007
- Study completionAug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00082446
- Sponsor's protocol ID
- 02-017
- Other IDs
- POX-MVA-002
- Status last verified
- Sep 2008
- First submitted
- 10 May 2004
- Last updated
- 19 Dec 2014
- Results posted
- No
Publications
Elizaga ML, Vasan S, Marovich MA, Sato AH, Lawrence DN, Chaitman BR, Frey SE, Keefer MC; MVA Cardiac Safety Working Group. Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review. PLoS One. 2013;8(1):e54407. doi: 10.1371/journal.pone.0054407. Epub 2013 Jan 17.
PubMed 23349878
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of MVA-BN in a Dose Response Regimen Followed by Administration of Dryvax in Healthy Adult Volunteers
- ClinicalTrials.gov ID
- NCT00082446
- Acronym / sponsor ID
- 02-017
- Conditions
- Smallpox
- Keywords
- Smallpox, vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- May 2004
- Primary completion
- Aug 2007 (actual)
- Study completion
- Aug 2007 (actual)
- First posted
- 11 May 2004 (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 overall goals of this study are to expand the available data on the safety and immunogenicity of MVA-BN in vaccinia-naive adults and to determine the optimum dose of MVA-BN to induce immune responses and attenuate Dryvax take reactions. Participants will include 90 healthy volunteers, ages 18-32 years. Participants will be randomly assigned to 1 of 6 study groups (groups A-F). Participants will be involved in study related procedures for up to 2 years. During this time, volunteers will return periodically for blood draws to check immune responses.
Detailed description
The primary goal of this phase I trial is to expand the available data on the safety and immunogenicity of MVA-BN in vaccinia-naïve adults. The secondary goals of this vaccine trial are: to determine the optimum dose of MVA-BN, given twice, to induce an immune response and attenuate Dryvax® take reactions; and to compare the ability of 2 routes of administration of MVA-BN, subcutaneous and intramuscular, to induce an immune response at the highest tested dose. A total of 90 healthy adult volunteers ages 18-32 will participate in this study. The volunteers will be randomly assigned to 1 of 6 groups to be immunized with: MVA-BN (subcutaneously) at 1 of 3 dose levels and Dryvax® (per scarification); placebo (subcutaneously) and Dryvax® (per scarification); MVA-BN (subcutaneously) at the highest dose level and placebo scarification; or MVA-BN (intramuscularly) at the highest dose level and Dryvax® (per scarification). The study will last about 30 months. Each volunteer's participation will last 6 months for all treatment groups. Subjects randomized to treatment groups D and E will have follow-up for 2 years. During this time, volunteers will return periodically for blood draws to check immune responses. Subjects will require visits for dressing changes as needed post-Dryvax vaccination. Variables to be investigated include: adverse events and side effects to the vaccines, and immunogenicity testing including antibody and cellular responses to the vaccines.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| E | Experimental | Biological: MVA Smallpox Vaccine, Other: PlaceboSubject will receive an SC dose of MVA 1x10^8 on day 0 and day 28. On day 112 subjects will receive a dose of placebo by scarification. |
| D | Active comparator | Biological: Live vaccinia virus vaccine, Other: PlaceboSubject will receive a SC dose of placebo on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification. |
| C | Experimental | Biological: Live vaccinia virus vaccine, Biological: MVA Smallpox VaccineSubject will receive a SC dose of MVA 1x10^8 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification. |
| B | Experimental | Biological: Live vaccinia virus vaccine, Biological: MVA Smallpox VaccineSubjects will receive a SC dose of MVA 5x10^7 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification. |
| A | Experimental | Biological: Live vaccinia virus vaccine, Biological: MVA Smallpox VaccineSubjects will receive a SC dose of MVA 2x10^7 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification. |
| F | Experimental | Biological: Live vaccinia virus vaccine, Biological: MVA Smallpox VaccineSubject will receive an IM dose of MVA 1x10^8 on day 0 and day 28. On day 112 subjects will receive a dose of Dryvax® by scarification. |
Who may qualify
- Ages
- 18 to 32 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- Ages 18-32.
- Never received smallpox vaccination.
- Read, signed and dated informed consent document.
- Availability for follow-up for the planned duration of the study two years after first immunization.
- Acceptable medical history by screening evaluation and limited physical examination.
Key exclusion criteria (32 listed)
- History of immunodeficiency.
- Typical vaccinia scar.
- Known or suspected history of smallpox vaccination.
- Military service prior to 1989 or after January 2003.
- Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
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®: 0.25 mL of vaccine will be administered by the standard route of scarification using a bifurcated needle on day 112 for Groups A, B, C, D and F. | Biological | A, B, C, D, F |
| MVA Smallpox VaccineImvamune/MVA-BN 1x10^8 will be administered intramuscularly to Group F on day 0 and day 28. | Biological | F |
| MVA Smallpox VaccineImvamune/MVA-BN Groups A, B C and E will be administered subcutaneously: 2x10^7, 5x10^7, 1x10^8, 1x10^8, respectively, on days 0 and day 28. | Biological | A, B, C, E |
| PlaceboGroup E will receive sterile saline placebo for injection via scarification on day 112. | Other | E |
| PlaceboGroup D will receive sterile saline placebo for injection subcutaneously on day 0 and day 28. | Other | D |
Primary outcome
Adverse Events and side effects to the vaccines.
Time frame: Reactogenicity will be evaluated for a 2-week period post-vaccination at each time point and for the duration of study.
1 secondary outcome
Immunogenicity testing of antibody and cellular responses to the vaccines.
Time frame: Visit days 0, 14, 28, 42, 56, 112, 140, 182, 365, and 730.
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 19 Dec 2014.
- Results publication: PubMed 23349878Elizaga ML, Vasan S, Marovich MA, Sato AH, Lawrence DN, Chaitman BR, Frey SE, Keefer MC; MVA Cardiac Safety Working Group. Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review. PLoS One. 2013;8(1):e54407. doi: 10.1371/journal.pone.0054407. Epub 2013 Jan 17.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Live vaccinia virus vaccine and MVA Smallpox Vaccine in people with Smallpox, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 16 inclusion and 32 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 19 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 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Adverse Events and side effects to the vaccines. (time frame: Reactogenicity will be evaluated for a 2-week period post-vaccination at each time point and for the duration of study.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00082446, which also lists 1 linked publication.
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 19 Dec 2014; AzTrials last refreshed its copy on 30 Oct 2026.