SmallpoxPhase 2NCT00879762
High Dose IMVAMUNE® in Vaccinia-Naive Individuals
A Phase 2 study testing MVA Smallpox Vaccine in people with Smallpox, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial summary
The purpose of this research is to compare the ability of a new investigational smallpox vaccine called IMVAMUNE® to produce a strong immune response against smallpox disease if given as one single, higher dose compared with two lower doses given one month apart. 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?
- 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
- 2 sitesUnited States
- Study dates
- 29 May 2009to 9 Mar 2011
- Phase
- Phase 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
- Prior to initial vaccination: -At least 18 years of age and born after 1971 -Read, sign, and date informed consent document -Available for follow-up for the planned duration of the study (six months 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 28 days following the last vaccination a. A woman is considered of childbearing potential unless post-menopausal (> 1 year) or surgically sterilized (tubal ligation, bilateral oophorectomy, or hysterectomy) b. Acceptable contraception methods are restricted to effective devices (IUDs, NuvaRing®) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, abstinence from sexual intercourse with men (vaginal penetration by a penis, coitus), and monogamous relationship with a vasectomized partner. -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+ by dipstick or urinalysis -Adequate renal function is defined as a serum creatinine not exceeding the institution's upper limit of normal. - Electrocardiogram (ECG) in absence of clinical significance [e.g., complete left or right bundle branch block, incomplete left bundle branch block or sustained ventricular arrhythmia, or two premature ventricular contractions (PVC's) in a row, or sympathetic tonus (ST) elevation consistent with ischemia] -The following blood parameters: a. Hemoglobin equal or above the lower limit of institutional normal (sex specific); b. White blood cells greater than 2,500 and less than 11,000/mm^3; c. Platelets greater than or equal to 140,000/mm^3 -Weight greater than or equal to 110 pounds Inclusion Criteria that must be met prior to the second vaccination: -Acceptable medical history -ECG (obtained after Day 14 after first vaccination) in absence of clinical significance (e.g., complete left or right bundle branch block, incomplete left bundle branch block or sustained ventricular arrhythmia, or two PVC's in a row, or ST elevation consistent with ischemia) -If the subject is female and of childbearing potential, 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 28 days following the last vaccination a. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized b. Acceptable contraception methods are restricted to effective devices (IUDs, 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)
Who cannot join
- Exclusion criteria that apply prior to the initial vaccination: -History of immunodeficiency -Typical vaccinia scar -Known or suspected history of smallpox vaccination including Modified Vaccinia Ankara (MVA) alone or as a vector as well as other investigational smallpox vaccine -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 a. 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 -Systolic blood pressure >/= 150 mmHg or diastolic blood pressure >/= 100 mmHg. -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. -High-dose steroid use for greater than 2 weeks duration within three months prior to vaccination and 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 or planned receipt of inactivated vaccine from 14 days prior to the first vaccination through 14 days post second vaccination -Receipt or planned receipt of any other live attenuated vaccine within 30 days prior to the first vaccination through 30 days post second vaccination -Use of any other experimental agent within 30 days prior to vaccination and for the duration of the study -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 prior to Visit 9 -Acute febrile illness (greater than or equal to 100.5 degrees Fahrenheit) on the day of vaccination -Pregnant or lactating women -Eczema of any degree or history of eczema -People with active atopic dermatitis, active 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 (including gentamicin) -Study personnel Exclusion criteria that apply prior to the second vaccination: -History of immunodeficiency -Known or suspected impairment of immunologic function including, but not limited to, clinically sig nificant 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 a. 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 -Systolic blood pressure >/= 150 mmHg or diastolic blood pressure >/=100 mmHg -High-dose steroid use for greater than 2 weeks duration within three months prior to vaccination and 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 or planned receipt of inactivated vaccine from 14 days prior to vaccination through 14 days post second vaccination -Receipt or planned receipt of any other live attenuated vaccine from 30 days prior to vaccination through 30 days post second vaccination -Use of any other experimental agent within 30 days prior to vaccination and for the duration of the study -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 prior to Visit 9 -Acute febrile illness (greater than or equal to 100.4 degrees Fahrenheit) on the day of vaccination -Pregnant or lactating women -Eczema of any degree or history of eczema -People with active atopic dermatitis, active 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 (including gentamicin)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Iowa - Vaccine Research and Education Unit
Iowa City, Iowa, 52242-2600
Saint Louis University Center for Vaccine Development
St Louis, Missouri, 63104-1015
About this study
Official title: Comparison of Safety and Immunogenicity of a High Dose (5 x 10^8 TCID50) and a Standard Dose (1 x 10^8 TCID50) of IMVAMUNE® in Healthy Vaccinia-Naive Individuals
The purpose of this research is to compare the ability of a new investigational smallpox vaccine called IMVAMUNE® to produce a strong immune response against smallpox disease if given as one single, higher dose compared with two lower doses given one month apart. Another purpose of the study is to see how quickly someone might be protected against smallpox. Volunteers will be vaccinia-naïve adults age 18 and older (born after 1971) divided into 2 groups. Volunteers in Group A will receive a high dose of vaccine given in 2 shots on day 0 followed by a placebo (inactive substance) shot on day 28. Group B will receive the standard dose of vaccine and placebo given in 2 shots on day 0 followed by a standard dose shot on Day 28. Study participation will include 10 planned study visits over approximately 7 months.
Read the detailed description
Despite the fact that the World Health Organization (WHO) officially declared smallpox to be eradicated, a new threat exists due to the potential use of variola virus as an agent for biological warfare and/or bio-terrorism. As a consequence, there is an urgent need for a safe and efficacious vaccine to protect the public against smallpox. To date, the majority of clinical studies with Modified Vaccinia Ankara (MVA) have studied a prime-boost vaccination regimen, with a dose of up to 1×10^8 tissue culture infectious dose 50 (TCID50) of MVA administered on Days 0 and 28. While this vaccination regimen induces a robust immune response that is protective in a variety of animal models and is appropriate for a pre-smallpox release scenario, in the event of a confirmed release of smallpox, a more rapid vaccination regimen that provides a protective immune response would be desirable. Ideally, at least short-term protection could be obtained with a single dose of vaccine. While a single dose of MVA at 1×10^8 TCID50, does induce an immune response in the majority of recipients, it is possible that a higher dose of MVA could provide a more rapid and/or stronger immune response relative to a single, standard 1×10^8 TCID50 dose of MVA. The goal of this study is to examine the kinetics and magnitude of the immune response of a single high dose of MVA (5×10^8 TCID50) relative to both a single and prime/boost regimen using the standard doses (1×10^8 TCID50) of MVA. This study will complement a current, ongoing study, DMID Protocol 06-0012, which is examining the immune response to compressed prime/boost dosing regimens of MVA administered at (1×10^8 TCID50). Upon the completion of these studies, clinical data will be generated which will inform policy makers about different options for post-event utilization of available smallpox vaccines. The study is designed as a randomized, non-placebo controlled, double blinded study containing two arms: Group A (N=45) will receive a single high dose of IMVAMUNE® (5x10^8 TCID50, consisting of two 0.5 mL injections) vaccine on Day 0 and a single saline placebo dose (single 0.5 mL injection) on Day 28 to match the two dose regimen of Group B. Group B (N=45) will receive a standard two dose regimen of IMVAMUNE® (1x10^8 TCID50) vaccine on Day 0 (consisting of 0.5 mL injection of vaccine and 0.5 mL injection of saline placebo) and Day 28 (single 0.5 mL injection of vaccine). Safety will be measured by assessment of adverse events for 28 days following the last vaccination (56 days following the initial vaccination for those subjects that fail to receive the second dose) and for serious adverse events at six months post the final vaccination, and reactogenicity to the vaccines for 15 days following each vaccination. Immunogenicity testing will include antibody testing [enzyme linked immunosorbent assay (ELISA) and plaque reduction neutralizing antibody titers (PRNT)] and cellular immune responses [(INF-gamma enzyme linked immunospot (ELISPOT)] following each vaccination and at six months post the final vaccination. In addition, ELISA responses, using MVA VR-1508 as the target antigen and PRNT using vaccinia WR (Western Reserve) as the target antigen will be explored. Participants will include 90 healthy, vaccinia-naïve adults, aged 18 and older (born after 1971). Study duration will be approximately 13 months (7 months/subject).
- Conditions
- Smallpox
- Being tested
- 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.
MVA Smallpox VaccineBiological
IMVAMUNE® Vaccinia Vaccine, undiluted, delivered by subcutaneous route on Day 0 at high dose 5×10^8 TCID50 (5×10^8 TCID50 per 1.0 mL dose - administered as 2 x 0.5 mL.
PlaceboOther
0.5 mL injection of saline placebo administered with vaccine on Day 0 (Group B) or single saline placebo dose (single 0.5 mL injection) on Day 28 (Group A).
| Study group | Role | What they receive |
|---|---|---|
| Group A: High Dose | Experimental | Single high dose of IMVAMUNE® (5x10^8 TCID50, consisting of two 0.5 mL injections) vaccine on Day 0 and a single saline placebo dose (single 0.5 mL injection) on Day 28 to match the two dose regimen of Group B. Receives: Biological: MVA Smallpox Vaccine; Other: Placebo |
| Group B: Standard Dose | Active comparator | Standard two dose regimen of IMVAMUNE® (1x10^8 TCID50) vaccine on Day 0 (consisting of 0.5 mL injection of vaccine and 0.5 mL injection of saline placebo) and Day 28 (single 0.5 mL injection of vaccine). Receives: Biological: MVA Smallpox Vaccine; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Seroconversion After One Vaccination Using Bavarian Nordic's (BN) Enzyme Linked Immunosorbent Assay (ELISA) in the Intent-to-Treat (ITT) Population
Seroconversion is defined as a titer >= 50 or as a 2-fold or greater increase in titer from baseline if pre-vaccination titer was >= 50. Participants who did not seroconvert during the study were analyzed as right censored at the last sample collection date. Samples collected after the second vaccination were also analyzed as right censored.
Measured: Days 0, 4, 8, 14, 21, and 28 after first vaccination
Time to Seroconversion After One Vaccination Using BN ELISA in the Per Protocol Population
Seroconversion is defined as a titer >= 50 or as a 2-fold or greater increase in titer from baseline if pre-vaccination titer was >= 50. Participants who did not seroconvert during the study were analyzed as right censored at the last sample collection date. Samples collected after the second vaccination were also analyzed as right censored.
Measured: Days 0, 4, 8, 14, 21, and 28 after first vaccination
Frequency of Serious Adverse Events (SAEs) Related to Vaccination
The number of participants who experienced at least one SAE throughout the course of the study that was deemed related to the study vaccination. 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 180 after second vaccination (Day 208 after first vaccination)
Frequency of Non-Serious AEs Related to Vaccination
The number of participants who experienced at least one unsolicited non-serious AE of any severity from Day 0 to 28 days post second vaccination (56 days post first vaccination) that was deemed related to the study vaccination.
Measured: Day 0 after first vaccination to Day 28 after second vaccination (Day 56 after first vaccination)
Frequency of Local Solicited Reactogenicity AEs for Subjective Symptoms
Local solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Local subjective events included pain at injection site, itchiness at injection site, underarm pain, and underarm swelling and were graded on a 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 (Day 28 through Day 43 after first vaccination)
Frequency of Local Solicited Reactogenicity AEs for Measured Symptoms
Local solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Local measured events included erythema and induration at the vaccination site and were measured in millimeters.
Measured: Day 0 through Day 15 after first vaccination; Day 0 through Day 15 after second vaccination (Day 28 through Day 43 after first vaccination)
Frequency of Systemic Solicited Reactogenicity AEs
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 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 (Day 28 through Day 43 after first vaccination)
Secondary outcomes (2)
Peak Titer of Saint Louis University's (SLU) Plaque Reduction Neutralizing Antibody Titer (PRNT) Assay After First Vaccination in the ITT Population
The peak PRNT is defined as the largest titer among all available measurements post-first vaccination but prior to the second vaccination. Means and corresponding standard errors are calculated on the log2.5 scale.
Measured: Days 4, 8, 14, 21, and 28 after first vaccination
Peak Titer of SLU PRNT Assay After First Vaccination in the Per Protocol Population
The peak PRNT is defined as the largest titer among all available measurements post-first vaccination but prior to the second vaccination. Means and corresponding standard errors are calculated on the log2.5 scale.
Measured: Days 4, 8, 14, 21, and 28 after first vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2009 (estimated)
- Study start29 May 2009
- Primary completion9 Mar 2011
- Study completion9 Mar 2011
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.
- 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
- 91 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00879762
- Sponsor's protocol ID
- 08-0040
- Status last verified
- 26 Jan 2012
- First submitted
- 9 Apr 2009
- Last updated
- 13 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Safety and Immunogenicity of a High Dose (5 x 10^8 TCID50) and a Standard Dose (1 x 10^8 TCID50) of IMVAMUNE® in Healthy Vaccinia-Naive Individuals
- ClinicalTrials.gov ID
- NCT00879762
- Acronym / sponsor ID
- 08-0040
- Conditions
- Smallpox
- Keywords
- IMVAMUNE®, smallpox, vaccine
- Phase
- Phase 2
- 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
- 29 May 2009 (actual)
- Primary completion
- 9 Mar 2011 (actual)
- Study completion
- 9 Mar 2011 (actual)
- First posted
- 10 Apr 2009 (estimated)
- Results
- Posted 13 Jun 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 research is to compare the ability of a new investigational smallpox vaccine called IMVAMUNE® to produce a strong immune response against smallpox disease if given as one single, higher dose compared with two lower doses given one month apart. Another purpose of the study is to see how quickly someone might be protected against smallpox. Volunteers will be vaccinia-naïve adults age 18 and older (born after 1971) divided into 2 groups. Volunteers in Group A will receive a high dose of vaccine given in 2 shots on day 0 followed by a placebo (inactive substance) shot on day 28. Group B will receive the standard dose of vaccine and placebo given in 2 shots on day 0 followed by a standard dose shot on Day 28. Study participation will include 10 planned study visits over approximately 7 months.
Detailed description
Despite the fact that the World Health Organization (WHO) officially declared smallpox to be eradicated, a new threat exists due to the potential use of variola virus as an agent for biological warfare and/or bio-terrorism. As a consequence, there is an urgent need for a safe and efficacious vaccine to protect the public against smallpox. To date, the majority of clinical studies with Modified Vaccinia Ankara (MVA) have studied a prime-boost vaccination regimen, with a dose of up to 1×10^8 tissue culture infectious dose 50 (TCID50) of MVA administered on Days 0 and 28. While this vaccination regimen induces a robust immune response that is protective in a variety of animal models and is appropriate for a pre-smallpox release scenario, in the event of a confirmed release of smallpox, a more rapid vaccination regimen that provides a protective immune response would be desirable. Ideally, at least short-term protection could be obtained with a single dose of vaccine. While a single dose of MVA at 1×10^8 TCID50, does induce an immune response in the majority of recipients, it is possible that a higher dose of MVA could provide a more rapid and/or stronger immune response relative to a single, standard 1×10^8 TCID50 dose of MVA. The goal of this study is to examine the kinetics and magnitude of the immune response of a single high dose of MVA (5×10^8 TCID50) relative to both a single and prime/boost regimen using the standard doses (1×10^8 TCID50) of MVA. This study will complement a current, ongoing study, DMID Protocol 06-0012, which is examining the immune response to compressed prime/boost dosing regimens of MVA administered at (1×10^8 TCID50). Upon the completion of these studies, clinical data will be generated which will inform policy makers about different options for post-event utilization of available smallpox vaccines. The study is designed as a randomized, non-placebo controlled, double blinded study containing two arms: Group A (N=45) will receive a single high dose of IMVAMUNE® (5x10^8 TCID50, consisting of two 0.5 mL injections) vaccine on Day 0 and a single saline placebo dose (single 0.5 mL injection) on Day 28 to match the two dose regimen of Group B. Group B (N=45) will receive a standard two dose regimen of IMVAMUNE® (1x10^8 TCID50) vaccine on Day 0 (consisting of 0.5 mL injection of vaccine and 0.5 mL injection of saline placebo) and Day 28 (single 0.5 mL injection of vaccine). Safety will be measured by assessment of adverse events for 28 days following the last vaccination (56 days following the initial vaccination for those subjects that fail to receive the second dose) and for serious adverse events at six months post the final vaccination, and reactogenicity to the vaccines for 15 days following each vaccination. Immunogenicity testing will include antibody testing [enzyme linked immunosorbent assay (ELISA) and plaque reduction neutralizing antibody titers (PRNT)] and cellular immune responses [(INF-gamma enzyme linked immunospot (ELISPOT)] following each vaccination and at six months post the final vaccination. In addition, ELISA responses, using MVA VR-1508 as the target antigen and PRNT using vaccinia WR (Western Reserve) as the target antigen will be explored. Participants will include 90 healthy, vaccinia-naïve adults, aged 18 and older (born after 1971). Study duration will be approximately 13 months (7 months/subject).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: High Dose | Experimental | Biological: MVA Smallpox Vaccine, Other: PlaceboSingle high dose of IMVAMUNE® (5x10^8 TCID50, consisting of two 0.5 mL injections) vaccine on Day 0 and a single saline placebo dose (single 0.5 mL injection) on Day 28 to match the two dose regimen of Group B. |
| Group B: Standard Dose | Active comparator | Biological: MVA Smallpox Vaccine, Other: PlaceboStandard two dose regimen of IMVAMUNE® (1x10^8 TCID50) vaccine on Day 0 (consisting of 0.5 mL injection of vaccine and 0.5 mL injection of saline placebo) and Day 28 (single 0.5 mL injection of vaccine). |
Who may qualify
- Ages
- 18 to 38 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Prior to initial vaccination: -At least 18 years of age and born after 1971 -Read, sign, and date informed consent document -Available for follow-up for the planned duration of the study (six months 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 28 days following the last vaccination a. A woman is considered of childbearing potential unless post-menopausal (> 1 year) or surgically sterilized (tubal ligation, bilateral oophorectomy, or hysterectomy) b. Acceptable contraception methods are restricted to effective devices (IUDs, NuvaRing®) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, abstinence from sexual intercourse with men (vaginal penetration by a penis, coitus), and monogamous relationship with a vasectomized partner. -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+ by dipstick or urinalysis -Adequate renal function is defined as a serum creatinine not exceeding the institution's upper limit of normal. - Electrocardiogram (ECG) in absence of clinical significance [e.g., complete left or right bundle branch block, incomplete left bundle branch block or sustained ventricular arrhythmia, or two premature ventricular contractions (PVC's) in a row, or sympathetic tonus (ST) elevation consistent with ischemia] -The following blood parameters: a. Hemoglobin equal or above the lower limit of institutional normal (sex specific); b. White blood cells greater than 2,500 and less than 11,000/mm^3; c. Platelets greater than or equal to 140,000/mm^3 -Weight greater than or equal to 110 pounds Inclusion Criteria that must be met prior to the second vaccination: -Acceptable medical history -ECG (obtained after Day 14 after first vaccination) in absence of clinical significance (e.g., complete left or right bundle branch block, incomplete left bundle branch block or sustained ventricular arrhythmia, or two PVC's in a row, or ST elevation consistent with ischemia) -If the subject is female and of childbearing potential, 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 28 days following the last vaccination a. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized b. Acceptable contraception methods are restricted to effective devices (IUDs, 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)
Key exclusion criteria (1 listed)
- Exclusion criteria that apply prior to the initial vaccination: -History of immunodeficiency -Typical vaccinia scar -Known or suspected history of smallpox vaccination including Modified Vaccinia Ankara (MVA) alone or as a vector as well as other investigational smallpox vaccine -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 a. 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 -Systolic blood pressure >/= 150 mmHg or diastolic blood pressure >/= 100 mmHg. -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. -High-dose steroid use for greater than 2 weeks duration within three months prior to vaccination and 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 or planned receipt of inactivated vaccine from 14 days prior to the first vaccination through 14 days post second vaccination -Receipt or planned receipt of any other live attenuated vaccine within 30 days prior to the first vaccination through 30 days post second vaccination -Use of any other experimental agent within 30 days prior to vaccination and for the duration of the study -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 prior to Visit 9 -Acute febrile illness (greater than or equal to 100.5 degrees Fahrenheit) on the day of vaccination -Pregnant or lactating women -Eczema of any degree or history of eczema -People with active atopic dermatitis, active 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 (including gentamicin) -Study personnel Exclusion criteria that apply prior to the second vaccination: -History of immunodeficiency -Known or suspected impairment of immunologic function including, but not limited to, clinically sig nificant 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 a. 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 -Systolic blood pressure >/= 150 mmHg or diastolic blood pressure >/=100 mmHg -High-dose steroid use for greater than 2 weeks duration within three months prior to vaccination and 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 or planned receipt of inactivated vaccine from 14 days prior to vaccination through 14 days post second vaccination -Receipt or planned receipt of any other live attenuated vaccine from 30 days prior to vaccination through 30 days post second vaccination -Use of any other experimental agent within 30 days prior to vaccination and for the duration of the study -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 prior to Visit 9 -Acute febrile illness (greater than or equal to 100.4 degrees Fahrenheit) on the day of vaccination -Pregnant or lactating women -Eczema of any degree or history of eczema -People with active atopic dermatitis, active 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 (including gentamicin)
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 |
|---|---|---|
| MVA Smallpox VaccineIMVAMUNE® Vaccinia Vaccine, undiluted, delivered by subcutaneous route on Day 0 at high dose 5×10^8 TCID50 (5×10^8 TCID50 per 1.0 mL dose - administered as 2 x 0.5 mL. | Biological | Group A: High Dose, Group B: Standard Dose |
| Placebo0.5 mL injection of saline placebo administered with vaccine on Day 0 (Group B) or single saline placebo dose (single 0.5 mL injection) on Day 28 (Group A). | Other | Group A: High Dose, Group B: Standard Dose |
Primary outcome
Time to Seroconversion After One Vaccination Using Bavarian Nordic's (BN) Enzyme Linked Immunosorbent Assay (ELISA) in the Intent-to-Treat (ITT) Population
Time frame: Days 0, 4, 8, 14, 21, and 28 after first vaccination
Seroconversion is defined as a titer >= 50 or as a 2-fold or greater increase in titer from baseline if pre-vaccination titer was >= 50. Participants who did not seroconvert during the study were analyzed as right censored at the last sample collection date. Samples collected after the second vaccination were also analyzed as right censored.
Time to Seroconversion After One Vaccination Using BN ELISA in the Per Protocol Population
Time frame: Days 0, 4, 8, 14, 21, and 28 after first vaccination
Seroconversion is defined as a titer >= 50 or as a 2-fold or greater increase in titer from baseline if pre-vaccination titer was >= 50. Participants who did not seroconvert during the study were analyzed as right censored at the last sample collection date. Samples collected after the second vaccination were also analyzed as right censored.
Frequency of Serious Adverse Events (SAEs) Related to Vaccination
Time frame: Day 0 after first vaccination to study completion through Day 180 after second vaccination (Day 208 after first vaccination)
The number of participants who experienced at least one SAE throughout the course of the study that was deemed related to the study vaccination. 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 Related to Vaccination
Time frame: Day 0 after first vaccination to Day 28 after second vaccination (Day 56 after first vaccination)
The number of participants who experienced at least one unsolicited non-serious AE of any severity from Day 0 to 28 days post second vaccination (56 days post first vaccination) that was deemed related to the study vaccination.
Frequency of Local Solicited Reactogenicity AEs for Subjective Symptoms
Time frame: Day 0 through Day 15 after first vaccination; Day 0 through Day 15 after second vaccination (Day 28 through Day 43 after first vaccination)
Local solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Local subjective events included pain at injection site, itchiness at injection site, underarm pain, and underarm swelling and were graded on a scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
Frequency of Local Solicited Reactogenicity AEs for Measured Symptoms
Time frame: Day 0 through Day 15 after first vaccination; Day 0 through Day 15 after second vaccination (Day 28 through Day 43 after first vaccination)
Local solicited reactogenicity AEs were collected daily for 15 days post each vaccination using a memory aid. Local measured events included erythema and induration at the vaccination site and were measured in millimeters.
Frequency of Systemic Solicited Reactogenicity AEs
Time frame: Day 0 through Day 15 after first vaccination; Day 0 through Day 15 after second vaccination (Day 28 through Day 43 after first 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 scale of Grade 0 (None), Grade 1 (Mild), Grade 2 (Moderate), and Grade 3 (Severe).
2 secondary outcomes
Peak Titer of Saint Louis University's (SLU) Plaque Reduction Neutralizing Antibody Titer (PRNT) Assay After First Vaccination in the ITT Population
Time frame: Days 4, 8, 14, 21, and 28 after first vaccination
Peak Titer of SLU PRNT Assay After First Vaccination in the Per Protocol Population
Time frame: Days 4, 8, 14, 21, and 28 after first vaccination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
2 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 MVA Smallpox Vaccine in people with Smallpox, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 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 13 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Yes. Results are posted in the registry (first posted 13 Jun 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?
Time to Seroconversion After One Vaccination Using Bavarian Nordic's (BN) Enzyme Linked Immunosorbent Assay (ELISA) in the Intent-to-Treat (ITT) Population (time frame: Days 0, 4, 8, 14, 21, and 28 after first vaccination). The study lists 7 primary outcomes in all. 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 13 Jun 2025.