SmallpoxPhase 1/2NCT00437021
MVA Post-Event: Administration Timing and Boost Study
A Phase 1/2 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 7 sites in United States.
Trial summary
The purpose of this study is to evaluate an investigational smallpox vaccine, called IMVAMUNE®, with respect to safety and immune (body's defense system) response. Participants will include healthy adults, age 18 or older born after 1971, who have not had smallpox vaccine before. Read more about this study
- Who is it for?
- Ages 18 to 38 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
- 226 participants
- Where
- 7 sitesUnited States
- Study dates
- 16 Apr 2007to 21 Apr 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 38 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- -At least 18 years of age and born after 1971 -Never received smallpox vaccination -Read, signed, and dated informed consent document -Available for follow-up for the planned duration of the study (one year after last immunization) -Acceptable medical history by screening evaluation and limited physical assessment -If the subject is female and of childbearing potential, negative serum pregnancy test at screening and negative urine or serum pregnancy test within 24 hours prior to vaccination -If the subject is female and of childbearing potential, she agrees to use acceptable contraception, and not become pregnant for the duration of the study a. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized b. Acceptable contraception methods are restricted to effective devices (e.g., Intrauterine Devices (IUD)s, NuvaRing®) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, and abstinence from sexual intercourse with men (vaginal penetration by a penis, coitus) c. Women who are not sexually active must agree to use one of the acceptable contraception methods if they are of childbearing potential -Negative enzyme linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) -Alanine aminotransferase (ALT) <1.25 times institutional upper limit of normal -Negative hepatitis B surface antigen and negative antibody to hepatitis C virus -Negative urine glucose and urine protein <1 plus by dipstick or urinalysis Adequate renal function defined as a serum creatinine equal to or less than the institutional upper limit of normal by gender; and urine protein <30 mg/dL or trace proteinuria (by urinalysis or dip stick). -Electrocardiogram (ECG) in absence of clinical significance (e.g., complete left or right bundle branch block, incomplete left bundle branch block or sustained ventricular arrythmia, or two premature ventricular contractions (PVC's) in a row, or sympathetic tonus (ST) elevation consistent with ischemia) -Complete blood count (CBC): Hemoglobin equal to or above the lower limit of institutional normal; White blood cells greater than or equal to 3200 /mm^3 and equal to or below the upper limit of institutional normal Platelets equal to or above the lower limit of institutional normal -Weight: greater than or equal to 110 pounds
Who cannot join
- -History of immunodeficiency -Typical vaccinia scar -Known or suspected history of smallpox vaccination -Military service prior to 1991 or after January 2003 -Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease, diabetes mellitus, or moderate to severe kidney impairment -Malignancy not including squamous cell skin cancer or basal cell skin cancer unless at the vaccination site or history of skin cancer at the vaccination site -Active autoimmune disease Persons with vitiligo or thyroid disease (e.g., taking thyroid hormone replacement) are not excluded. -History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor -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 (http://hin.nhlbi.nih.gov/atpiii/calculator.asp) -NOTE that this criterion applies only to subjects 20 years of age and older AND only if at least one of the following apply: a. have smoked a cigarette in the past month, and/or b. have hypertension (defined as systolic blood pressure >140 mm Hg) or are on antihypertensive medication, and/or c. have a family history of coronary heart disease in male first-degree relative (father or brother) <55 years of age or a female first-degree relative (mother or sister) <65 years of age. -Current use of immunosuppressive medication a. Corticosteroid nasal sprays are permissible b. Persons who are using a topical steroid can be enrolled after their therapy is completed c. Inhaled steroids for asthma are not permissible -Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol -Any history of illegal injection drug use -Receipt of inactivated vaccine 14 days prior to vaccination -Receipt of live attenuated vaccine within 30 days prior to vaccination -Use of experimental agent within 30 days prior to vaccination -Receipt of blood products or immunoglobulin within six months prior to vaccination -Donation of a unit of blood within 56 days prior to vaccination or for the duration of the study -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, chronic exfoliative skin disorders/conditions, current Varicella zoster, or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2×2 cm -Any condition that, in the opinion of the investigator, might interfere with study objectives -Known allergy to IMVAMUNE® vaccine -Known allergy to egg or aminoglycoside -Study personnel
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Maryland, School of Medicine, Center for Vaccine Development and Global Health
Baltimore, Maryland, 21201-1509
Case Western Reserve University - John T. Carey Special Immunology Unit
Cleveland, Ohio, 44106-3808
Duke Translational Medicine Institute - Clinical Vaccine Unit
Durham, North Carolina, 27704-2120
University of Texas Medical Branch - Pediatrics - Infectious Diseases and Immunology - Galveston
Galveston, Texas, 77555-5302
University of Iowa - Vaccine Research and Education Unit
Iowa City, Iowa, 52242-2600
University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases
Rochester, New York, 14642-0001
Saint Louis University Center for Vaccine Development
St Louis, Missouri, 63104-1015
About this study
Official title: Evaluation of IMVAMUNE® Smallpox Vaccine With Respect to Safety and Optimization of Immune Responses by Different Vaccination Regimens in Vaccinia-Naïve Adults
The purpose of this study is to evaluate an investigational smallpox vaccine, called IMVAMUNE®, with respect to safety and immune (body's defense system) response. Participants will include healthy adults, age 18 or older born after 1971, who have not had smallpox vaccine before. Participants were originally assigned to 1 of 5 groups. In July 2007, a hold was placed on the Dryvax® groups and the study was modified. Participants, will be assigned by chance to one of 3 groups to be vaccinated twice with IMVAMUNE® vaccine or placebo (inactive substance) in Groups A and B, or to receive a single vaccination with IMVAMUNE® or placebo in Group F. Participants will complete a memory aid (diary) for 15 days following vaccination. Blood samples will be collected. Participants may participate for up to 425 days.
Read the detailed description
The study will evaluate the IMVAMUNE® smallpox vaccine with respect to safety and optimization of immune responses by different vaccination regimens in vaccinia-naïve adults. Study participants must be age 18 and older and born after 1971. Originally, participants were planned to be randomly assigned to 1 of 5 groups to be immunized twice with IMVAMUNE® vaccine or placebo subcutaneously in Groups A and B, or Dryvax® or placebo by scarification in Group C or both IMVAMUNE® and Dryvax® or 2 placebos in Groups D and Group E. In July 2007, enrollment was halted at the request of Center for Biologics Evaluation and Research (CBER). At that time, enrollment included zero subjects in Group A, 2 subjects in Group B, 8 subjects in Group C, 6 subjects in Group D, and 4 subjects in Group E. CBER placed an official hold on the enrollment into the Groups that would administer Dryvax®, i.e., Groups C, D and E. Subjects previously enrolled into Groups C, D, and E will be followed according to the protocol. The protocol has been modified as follows. Participants will be randomly assigned to 1 of 3 groups to be immunized twice with IMVAMUNE® vaccine or placebo subcutaneously in Groups A and B, or to receive a single immunization with IMVAMUNE® or placebo subcutaneously in Group F. (NOTE: Group B will contain two additional participants that were enrolled prior to modification.) Group A will receive IMVAMUNE® vaccine or placebo on Days 0 and 7. Group B will receive IMVAMUNE® vaccine or placebo on Days 0 and 28. Group F will receive a single dose of IMVAMUNE® at Day 0. All participants will complete a memory aid for 15 days following each vaccination. Groups C, D, and E will have the appropriate reactogenicity information collected until the vaccination lesion, if present is well dried. Adverse events will be collected for 28 days after each vaccination. Specimens will be collected for immunologic assays at the noted clinic visits, as well as 1 year post last vaccination. Serious adverse events will be collected throughout the study period. The primary safety objective is to evaluate the safety of IMVAMUNE® given as a single dose, IMVAMUNE® given in a 2 dose prime-boost regimen at Day 0 and 7 or Day 0 and 28, IMVAMUNE® followed by a boost with Dryvax®, and IMVAMUNE® given simultaneously with Dryvax®. The primary immunogenicity objective is to determine if the Geometric Mean Titer (GMT) of neutralizing antibody [using Modified Vaccinia Ankara (MVA) as the target antigen] among subjects receiving a regimen of 2 doses of IMVAMUNE® (1×10^8, Days 0 and 7, Group A) is non-inferior to that among subjects receiving 2 doses of IMVAMUNE® (1×10^8, Days 0 and 28, Group B) at Day 14 following the 2nd dose. The secondary immunogenicity objective is to determine if the GMT, as assessed by enzyme linked immunosorbent assay (ELISA) (using MVA as the target antigen), among subjects receiving a regimen of 2 doses of IMVAMUNE® (1×10^8, Days 0 and 7, Group A) is non-inferior to that among subjects receiving 2 doses of IMVAMUNE® (1×10^8, Days 0 and 28, Group B) at Day 14 following the 2nd dose. The tertiary immunogenicity objective is to characterize the kinetics, magnitude, and duration of cellular and humoral immune responses to IMVAMUNE® alone or IMVAMUNE® as a prime followed by a boost with IMVAMUNE® or Dryvax®, or Dryvax® alone.
- Conditions
- Smallpox
- Being tested
- Live vaccinia virus vaccine, MVA Smallpox Vaccine, Placebo
- Keywords
- IMVAMUNE®, 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® Vaccinia Vaccine (~10^5 [plaque forming units (pfu)/dose] given via scarification, titer 10^8 pfu per mL after reconstitution).
MVA Smallpox VaccineBiological
IMVAMUNE® Vaccinia Vaccine delivered by subcutaneous (SC) route at titer 1X10^8 Tissue Culture Infections Dose50 per 0.5 mL dose.
PlaceboOther
0.9 percent (weight/volume) sodium chloride injection, United States Pharmacopeia [Sterile Saline Placebo (SSP)].
PlaceboOther
Physiologic normal saline for injection.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Standard dose IMVAMUNE® vaccine or placebo on Days 0 and 7. Receives: Biological: MVA Smallpox Vaccine; Other: Placebo |
| Group B | Experimental | Standard dose IMVAMUNE® vaccine or placebo on Days 0 and 28. Receives: Biological: MVA Smallpox Vaccine; Other: Placebo |
| Group C | Active comparator | Dryvax® vaccine or placebo on Day 0. This arm was discontinued from original protocol. Subjects already enrolled in this group will continue follow-up per protocol. Receives: Biological: Live vaccinia virus vaccine; Other: Placebo |
| Group D | Experimental | Standard dose IMVAMUNE® vaccine or placebo on Day 0 and Dryvax® vaccine or placebo on Day 7. This arm was discontinued from original protocol. Subjects already enrolled in this group will continue follow-up per protocol. Receives: Biological: Live vaccinia virus vaccine; Biological: MVA Smallpox Vaccine; Other: Placebo |
| Group E | Experimental | Dryvax® vaccine and standard dose IMVAMUNE® vaccine or 2 placebos on Day 0. This arm was discontinued from original protocol. Subjects already enrolled in this group will continue follow-up per protocol. Receives: Biological: Live vaccinia virus vaccine; Biological: MVA Smallpox Vaccine; Other: Placebo |
| Group F | Experimental | Standard dose IMVAMUNE® vaccine or placebo on Day 0. Receives: Biological: MVA Smallpox Vaccine; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric Mean Titer (GMT) of Bavarian Nordic's (BN) Plaque Reduction Neutralizing Antibody Titer (PRNT) Assay in Groups A and B
Geometric mean of titers collected 14 days after the second vaccination.
Measured: Day 14 after the second vaccination
GMT of Saint Louis University's (SLU) PRNT Assay in Group A and Group B
Geometric mean of titers collected 14 days after the second vaccination.
Measured: Day 14 after the second vaccination
Frequency of Serious Adverse Events (SAEs)
The number of participants who experienced at least one SAE throughout the course of the study. A SAE is defined as an AE meeting one of the following conditions:
- Death during the study period (from first vaccine until end of surveillance period)
- Life-threatening (defined as a participant at immediate risk of death at the time of the event)
- Requires inpatient hospitalization or prolongation of existing hospitalization during the period of protocol-defined surveillance
- Results in a congenital anomaly or birth defect
- Results in a persistent or significant disability/incapacity
- Severe adverse event associated with study product
Measured: Day 0 after first vaccination to study completion through Day 365 after last vaccination
Frequency of Non-Serious AEs
The number of participants who experienced at least one unsolicited non-serious AE of any severity from Day 0 after the first vaccination to 28 days after the last vaccination.
Measured: Day 0 after first vaccination through Day 28 after last vaccination
Frequency of Local Solicited Reactogenicity AEs for Groups A, B, and D and Placebo A, B, and D
Local solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Local events include pain at vaccination site, itchiness at vaccination site, rash at vaccination site underarm pain, underarm swelling, erythema, and induration. Erythema and induration at the vaccination site were measured in millimeters; the remaining events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Measured: Day 0 through Day 15 after first vaccination; Day 0 through Day 15 after second vaccination
Frequency of Local Solicited Reactogenicity AEs for Groups C and F and Placebo F
Local solicited reactogenicity AEs were collected daily for 15 days post vaccination using a memory aid. Local events include pain at vaccination site, itchiness at vaccination site, rash at vaccination site underarm pain, underarm swelling, erythema, and induration. Erythema and induration at the vaccination site were measured in millimeters; the remaining events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Measured: Day 0 through Day 15 after first vaccination
Frequency of Local Solicited Reactogenicity AEs for Group E and Placebo E
Local solicited reactogenicity AEs were collected daily for 15 days post vaccination using a memory aid. Results are reported by vaccination site (MVA Vaccination or Dryvax Vaccination). Local events included pain at vaccination site, itchiness at vaccination site, rash at vaccination site underarm pain, underarm swelling, erythema, and induration. Erythema and induration at the vaccination site were measured in millimeters; the remaining events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Measured: Day 0 through Day 15 after first vaccination
Frequency of Systemic Solicited Reactogenicity AEs for Groups A, B, and D and Placebo A, B, and D
Systemic solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Systemic events included muscle aches, chills, headache, nausea, feeling tired, change in appetite, joint pain, and elevated oral temperature. Events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Measured: Day 0 through Day 15 after first vaccination; Day 0 through Day 15 after second vaccination
Frequency of Systemic Solicited Reactogenicity AEs for Groups C, E, and F and Placebo E and F
Systemic solicited reactogenicity AEs were collected daily for 15 days post vaccination using a memory aid. Systemic events included muscle aches, chills, headache, nausea, feeling tired, change in appetite, joint pain, and elevated oral temperature. Events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Measured: Day 0 through Day 15 after first vaccination
Secondary outcomes (2)
GMT of BN Enzyme Linked Immunosorbent Assay (ELISA) in Groups A and B
Geometric mean of titers collected 14 days after the second vaccination.
Measured: Day 14 after the second vaccination
GMT of SLU ELISA in Groups A and B
Geometric mean of titers collected 14 days after the second vaccination.
Measured: Day 14 after the second vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2007 (estimated)
- Study start16 Apr 2007
- Primary completion21 Apr 2009
- Study completion21 Apr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 226 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00437021
- Sponsor's protocol ID
- 06-0012
- Status last verified
- 8 Mar 2010
- First submitted
- 16 Feb 2007
- Last updated
- 19 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Frey SE, Winokur PL, Salata RA, El-Kamary SS, Turley CB, Walter EB Jr, Hay CM, Newman FK, Hill HR, Zhang Y, Chaplin P, Tary-Lehmann M, Belshe RB. Safety and immunogenicity of IMVAMUNE(R) smallpox vaccine using different strategies for a post event scenario. Vaccine. 2013 Jun 24;31(29):3025-33. doi: 10.1016/j.vaccine.2013.04.050. Epub 2013 May 9.
PubMed 23664987
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of IMVAMUNE® Smallpox Vaccine With Respect to Safety and Optimization of Immune Responses by Different Vaccination Regimens in Vaccinia-Naïve Adults
- ClinicalTrials.gov ID
- NCT00437021
- Acronym / sponsor ID
- 06-0012
- Conditions
- Smallpox
- Keywords
- IMVAMUNE®, smallpox, vaccine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 226 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 16 Apr 2007 (actual)
- Primary completion
- 21 Apr 2009 (actual)
- Study completion
- 21 Apr 2009 (actual)
- First posted
- 19 Feb 2007 (estimated)
- Results
- Posted 19 Sep 2025
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 evaluate an investigational smallpox vaccine, called IMVAMUNE®, with respect to safety and immune (body's defense system) response. Participants will include healthy adults, age 18 or older born after 1971, who have not had smallpox vaccine before. Participants were originally assigned to 1 of 5 groups. In July 2007, a hold was placed on the Dryvax® groups and the study was modified. Participants, will be assigned by chance to one of 3 groups to be vaccinated twice with IMVAMUNE® vaccine or placebo (inactive substance) in Groups A and B, or to receive a single vaccination with IMVAMUNE® or placebo in Group F. Participants will complete a memory aid (diary) for 15 days following vaccination. Blood samples will be collected. Participants may participate for up to 425 days.
Detailed description
The study will evaluate the IMVAMUNE® smallpox vaccine with respect to safety and optimization of immune responses by different vaccination regimens in vaccinia-naïve adults. Study participants must be age 18 and older and born after 1971. Originally, participants were planned to be randomly assigned to 1 of 5 groups to be immunized twice with IMVAMUNE® vaccine or placebo subcutaneously in Groups A and B, or Dryvax® or placebo by scarification in Group C or both IMVAMUNE® and Dryvax® or 2 placebos in Groups D and Group E. In July 2007, enrollment was halted at the request of Center for Biologics Evaluation and Research (CBER). At that time, enrollment included zero subjects in Group A, 2 subjects in Group B, 8 subjects in Group C, 6 subjects in Group D, and 4 subjects in Group E. CBER placed an official hold on the enrollment into the Groups that would administer Dryvax®, i.e., Groups C, D and E. Subjects previously enrolled into Groups C, D, and E will be followed according to the protocol. The protocol has been modified as follows. Participants will be randomly assigned to 1 of 3 groups to be immunized twice with IMVAMUNE® vaccine or placebo subcutaneously in Groups A and B, or to receive a single immunization with IMVAMUNE® or placebo subcutaneously in Group F. (NOTE: Group B will contain two additional participants that were enrolled prior to modification.) Group A will receive IMVAMUNE® vaccine or placebo on Days 0 and 7. Group B will receive IMVAMUNE® vaccine or placebo on Days 0 and 28. Group F will receive a single dose of IMVAMUNE® at Day 0. All participants will complete a memory aid for 15 days following each vaccination. Groups C, D, and E will have the appropriate reactogenicity information collected until the vaccination lesion, if present is well dried. Adverse events will be collected for 28 days after each vaccination. Specimens will be collected for immunologic assays at the noted clinic visits, as well as 1 year post last vaccination. Serious adverse events will be collected throughout the study period. The primary safety objective is to evaluate the safety of IMVAMUNE® given as a single dose, IMVAMUNE® given in a 2 dose prime-boost regimen at Day 0 and 7 or Day 0 and 28, IMVAMUNE® followed by a boost with Dryvax®, and IMVAMUNE® given simultaneously with Dryvax®. The primary immunogenicity objective is to determine if the Geometric Mean Titer (GMT) of neutralizing antibody [using Modified Vaccinia Ankara (MVA) as the target antigen] among subjects receiving a regimen of 2 doses of IMVAMUNE® (1×10^8, Days 0 and 7, Group A) is non-inferior to that among subjects receiving 2 doses of IMVAMUNE® (1×10^8, Days 0 and 28, Group B) at Day 14 following the 2nd dose. The secondary immunogenicity objective is to determine if the GMT, as assessed by enzyme linked immunosorbent assay (ELISA) (using MVA as the target antigen), among subjects receiving a regimen of 2 doses of IMVAMUNE® (1×10^8, Days 0 and 7, Group A) is non-inferior to that among subjects receiving 2 doses of IMVAMUNE® (1×10^8, Days 0 and 28, Group B) at Day 14 following the 2nd dose. The tertiary immunogenicity objective is to characterize the kinetics, magnitude, and duration of cellular and humoral immune responses to IMVAMUNE® alone or IMVAMUNE® as a prime followed by a boost with IMVAMUNE® or Dryvax®, or Dryvax® alone.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Biological: MVA Smallpox Vaccine, Other: PlaceboStandard dose IMVAMUNE® vaccine or placebo on Days 0 and 7. |
| Group B | Experimental | Biological: MVA Smallpox Vaccine, Other: PlaceboStandard dose IMVAMUNE® vaccine or placebo on Days 0 and 28. |
| Group C | Active comparator | Biological: Live vaccinia virus vaccine, Other: PlaceboDryvax® vaccine or placebo on Day 0. This arm was discontinued from original protocol. Subjects already enrolled in this group will continue follow-up per protocol. |
| Group D | Experimental | Biological: Live vaccinia virus vaccine, Biological: MVA Smallpox Vaccine, Other: PlaceboStandard dose IMVAMUNE® vaccine or placebo on Day 0 and Dryvax® vaccine or placebo on Day 7. This arm was discontinued from original protocol. Subjects already enrolled in this group will continue follow-up per protocol. |
| Group E | Experimental | Biological: Live vaccinia virus vaccine, Biological: MVA Smallpox Vaccine, Other: PlaceboDryvax® vaccine and standard dose IMVAMUNE® vaccine or 2 placebos on Day 0. This arm was discontinued from original protocol. Subjects already enrolled in this group will continue follow-up per protocol. |
| Group F | Experimental | Biological: MVA Smallpox Vaccine, Other: PlaceboStandard dose IMVAMUNE® vaccine or placebo on Day 0. |
Who may qualify
- Ages
- 18 to 38 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- -At least 18 years of age and born after 1971 -Never received smallpox vaccination -Read, signed, and dated informed consent document -Available for follow-up for the planned duration of the study (one year after last immunization) -Acceptable medical history by screening evaluation and limited physical assessment -If the subject is female and of childbearing potential, negative serum pregnancy test at screening and negative urine or serum pregnancy test within 24 hours prior to vaccination -If the subject is female and of childbearing potential, she agrees to use acceptable contraception, and not become pregnant for the duration of the study a. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized b. Acceptable contraception methods are restricted to effective devices (e.g., Intrauterine Devices (IUD)s, NuvaRing®) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, and abstinence from sexual intercourse with men (vaginal penetration by a penis, coitus) c. Women who are not sexually active must agree to use one of the acceptable contraception methods if they are of childbearing potential -Negative enzyme linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) -Alanine aminotransferase (ALT) <1.25 times institutional upper limit of normal -Negative hepatitis B surface antigen and negative antibody to hepatitis C virus -Negative urine glucose and urine protein <1 plus by dipstick or urinalysis Adequate renal function defined as a serum creatinine equal to or less than the institutional upper limit of normal by gender; and urine protein <30 mg/dL or trace proteinuria (by urinalysis or dip stick). -Electrocardiogram (ECG) in absence of clinical significance (e.g., complete left or right bundle branch block, incomplete left bundle branch block or sustained ventricular arrythmia, or two premature ventricular contractions (PVC's) in a row, or sympathetic tonus (ST) elevation consistent with ischemia) -Complete blood count (CBC): Hemoglobin equal to or above the lower limit of institutional normal; White blood cells greater than or equal to 3200 /mm^3 and equal to or below the upper limit of institutional normal Platelets equal to or above the lower limit of institutional normal -Weight: greater than or equal to 110 pounds
Key exclusion criteria (1 listed)
- -History of immunodeficiency -Typical vaccinia scar -Known or suspected history of smallpox vaccination -Military service prior to 1991 or after January 2003 -Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease, diabetes mellitus, or moderate to severe kidney impairment -Malignancy not including squamous cell skin cancer or basal cell skin cancer unless at the vaccination site or history of skin cancer at the vaccination site -Active autoimmune disease Persons with vitiligo or thyroid disease (e.g., taking thyroid hormone replacement) are not excluded. -History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor -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 (http://hin.nhlbi.nih.gov/atpiii/calculator.asp) -NOTE that this criterion applies only to subjects 20 years of age and older AND only if at least one of the following apply: a. have smoked a cigarette in the past month, and/or b. have hypertension (defined as systolic blood pressure >140 mm Hg) or are on antihypertensive medication, and/or c. have a family history of coronary heart disease in male first-degree relative (father or brother) <55 years of age or a female first-degree relative (mother or sister) <65 years of age. -Current use of immunosuppressive medication a. Corticosteroid nasal sprays are permissible b. Persons who are using a topical steroid can be enrolled after their therapy is completed c. Inhaled steroids for asthma are not permissible -Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol -Any history of illegal injection drug use -Receipt of inactivated vaccine 14 days prior to vaccination -Receipt of live attenuated vaccine within 30 days prior to vaccination -Use of experimental agent within 30 days prior to vaccination -Receipt of blood products or immunoglobulin within six months prior to vaccination -Donation of a unit of blood within 56 days prior to vaccination or for the duration of the study -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, chronic exfoliative skin disorders/conditions, current Varicella zoster, or any acute skin disorders of large magnitude, e.g., laceration requiring sutures, burn greater than 2×2 cm -Any condition that, in the opinion of the investigator, might interfere with study objectives -Known allergy to IMVAMUNE® vaccine -Known allergy to egg or aminoglycoside -Study personnel
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® Vaccinia Vaccine (~10^5 [plaque forming units (pfu)/dose] given via scarification, titer 10^8 pfu per mL after reconstitution). | Biological | Group C, Group D, Group E |
| MVA Smallpox VaccineIMVAMUNE® Vaccinia Vaccine delivered by subcutaneous (SC) route at titer 1X10^8 Tissue Culture Infections Dose50 per 0.5 mL dose. | Biological | Group A, Group B, Group D, Group E, Group F |
| Placebo0.9 percent (weight/volume) sodium chloride injection, United States Pharmacopeia [Sterile Saline Placebo (SSP)]. | Other | Group A, Group B, Group D, Group E, Group F |
| PlaceboPhysiologic normal saline for injection. | Other | Group C, Group D, Group E |
Primary outcome
Geometric Mean Titer (GMT) of Bavarian Nordic's (BN) Plaque Reduction Neutralizing Antibody Titer (PRNT) Assay in Groups A and B
Time frame: Day 14 after the second vaccination
Geometric mean of titers collected 14 days after the second vaccination.
GMT of Saint Louis University's (SLU) PRNT Assay in Group A and Group B
Time frame: Day 14 after the second vaccination
Geometric mean of titers collected 14 days after the second vaccination.
Frequency of Serious Adverse Events (SAEs)
Time frame: Day 0 after first vaccination to study completion through Day 365 after last vaccination
The number of participants who experienced at least one SAE throughout the course of the study. A SAE is defined as an AE meeting one of the following conditions: * Death during the study period (from first vaccine until end of surveillance period) * Life-threatening (defined as a participant at immediate risk of death at the time of the event) * Requires inpatient hospitalization or prolongation of existing hospitalization during the period of protocol-defined surveillance * Results in a congenital anomaly or birth defect * Results in a persistent or significant disability/incapacity * Severe adverse event associated with study product
Frequency of Non-Serious AEs
Time frame: Day 0 after first vaccination through Day 28 after last vaccination
The number of participants who experienced at least one unsolicited non-serious AE of any severity from Day 0 after the first vaccination to 28 days after the last vaccination.
Frequency of Local Solicited Reactogenicity AEs for Groups A, B, and D and Placebo A, B, and D
Time frame: Day 0 through Day 15 after first vaccination; Day 0 through Day 15 after second vaccination
Local solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Local events include pain at vaccination site, itchiness at vaccination site, rash at vaccination site underarm pain, underarm swelling, erythema, and induration. Erythema and induration at the vaccination site were measured in millimeters; the remaining events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Frequency of Local Solicited Reactogenicity AEs for Groups C and F and Placebo F
Time frame: Day 0 through Day 15 after first vaccination
Local solicited reactogenicity AEs were collected daily for 15 days post vaccination using a memory aid. Local events include pain at vaccination site, itchiness at vaccination site, rash at vaccination site underarm pain, underarm swelling, erythema, and induration. Erythema and induration at the vaccination site were measured in millimeters; the remaining events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Frequency of Local Solicited Reactogenicity AEs for Group E and Placebo E
Time frame: Day 0 through Day 15 after first vaccination
Local solicited reactogenicity AEs were collected daily for 15 days post vaccination using a memory aid. Results are reported by vaccination site (MVA Vaccination or Dryvax Vaccination). Local events included pain at vaccination site, itchiness at vaccination site, rash at vaccination site underarm pain, underarm swelling, erythema, and induration. Erythema and induration at the vaccination site were measured in millimeters; the remaining events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Frequency of Systemic Solicited Reactogenicity AEs for Groups A, B, and D and Placebo A, B, and D
Time frame: Day 0 through Day 15 after first vaccination; Day 0 through Day 15 after second vaccination
Systemic solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Systemic events included muscle aches, chills, headache, nausea, feeling tired, change in appetite, joint pain, and elevated oral temperature. Events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Frequency of Systemic Solicited Reactogenicity AEs for Groups C, E, and F and Placebo E and F
Time frame: Day 0 through Day 15 after first vaccination
Systemic solicited reactogenicity AEs were collected daily for 15 days post vaccination using a memory aid. Systemic events included muscle aches, chills, headache, nausea, feeling tired, change in appetite, joint pain, and elevated oral temperature. Events were graded on a subjective scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
2 secondary outcomes
GMT of BN Enzyme Linked Immunosorbent Assay (ELISA) in Groups A and B
Time frame: Day 14 after the second vaccination
GMT of SLU ELISA in Groups A and B
Time frame: Day 14 after the second vaccination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23664987Frey SE, Winokur PL, Salata RA, El-Kamary SS, Turley CB, Walter EB Jr, Hay CM, Newman FK, Hill HR, Zhang Y, Chaplin P, Tary-Lehmann M, Belshe RB. Safety and immunogenicity of IMVAMUNE(R) smallpox vaccine using different strategies for a post event scenario. Vaccine. 2013 Jun 24;31(29):3025-33. doi: 10.1016/j.vaccine.2013.04.050. Epub 2013 May 9.
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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 1/2 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 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 1 inclusion and 1 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 Sep 2025. 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 combined 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.
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?
Yes. Results are posted in the registry (first posted 19 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Geometric Mean Titer (GMT) of Bavarian Nordic's (BN) Plaque Reduction Neutralizing Antibody Titer (PRNT) Assay in Groups A and B (time frame: Day 14 after the second vaccination). The study lists 9 primary outcomes in all. 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 NCT00437021, 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 Sep 2025.