A Phase 1/2 interventional study of Live vaccinia virus vaccine and MVA Smallpox Vaccine in Smallpox, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 7 sites in United States. Open to participants aged 18 Years to 38 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-09-19.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1/2, Interventional, and Prevention
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.
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.
73 studies on the registry are indexed under Smallpox; 5 are open to participants now.
This study's enrollment of 226 is above the median of 150 across 61 interventional studies indexed under Smallpox.
Browse Smallpox studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
-At least 18 years of age and born after 1971 -Never received smallpox vaccination -Read, signed, and dated 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 , 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 , and not become pregnant for the duration of the study a. A woman is considered of childbearing potential unless 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 (HIV) - (ALT) \<1.25 times institutional -Negative surface antigen and negative antibody to 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). - (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): 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 equal to or above the lower limit of institutional normal -Weight: greater than or equal to 110 pounds
Exclusion Criteria:
-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, liver disease, diabetes mellitus, or moderate to severe kidney impairment - 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 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 , 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 medication a. 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 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
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Standard dose IMVAMUNE® vaccine or placebo on Days 0 and 7.
Biological: MVA Smallpox Vaccine · Other: Placebo
Standard dose IMVAMUNE® vaccine or placebo on Days 0 and 28.
Biological: MVA Smallpox Vaccine · Other: Placebo
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.
Biological: Live vaccinia virus vaccine · Other: Placebo
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.
Biological: Live vaccinia virus vaccine · Biological: MVA Smallpox Vaccine · Other: Placebo
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.
Biological: Live vaccinia virus vaccine · Biological: MVA Smallpox Vaccine · Other: Placebo
Standard dose IMVAMUNE® vaccine or placebo on Day 0.
Biological: MVA Smallpox Vaccine · Other: Placebo
Dryvax® Vaccinia Vaccine (\~10\^5 \[plaque forming units (pfu)/dose\] given via scarification, titer 10\^8 pfu per mL after reconstitution).
IMVAMUNE® Vaccinia Vaccine delivered by subcutaneous (SC) route at titer 1X10\^8 Tissue Culture Infections Dose50 per 0.5 mL dose.
0.9 percent (weight/volume) sodium chloride injection, United States Pharmacopeia \[Sterile Saline Placebo (SSP)\].
Physiologic normal saline for injection.
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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: Day 0 through Day 15 after first vaccination
GMT of BN Enzyme Linked Immunosorbent Assay (ELISA) in Groups A and B
Geometric mean of titers collected 14 days after the second vaccination.
Time frame: 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.
Time frame: Day 14 after the second vaccination
The study population included adults aged greater than 18 years (and born after 1971) who met all inclusion/exclusion criteria. Participants were recruited from seven sites within the United States. The first participant was enrolled on April 16, 2007, and the last participant was enrolled on April 3, 2008.
| Milestone | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 | Group C: One Dose Dryvax, Day 0 | Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | Group E: IMVAMUNE + Dryvax, Day 0 | Group F: IMVAMUNE, Day 0 | Placebo A | Placebo B | Placebo C | Placebo D | Placebo E | Placebo F |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 61 | 66 | 8 | 5 | 2 | 63 | 6 | 5 | 0 | 1 | 2 | 7 |
| Completed | 59 | 62 | 8 | 5 | 2 | 61 | 5 | 4 | 0 | 1 | 2 | 7 |
| Not completed | 2 | 4 | 0 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 3 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Geometric mean of titers collected 14 days after the second vaccination.
| titer | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 |
|---|---|---|
| Geometric Mean Titer (GMT) of Bavarian Nordic's (BN) Plaque Reduction Neutralizing Antibody Titer (PRNT) Assay in Groups A and B | 10.8 (9.0 to 12.9) | 30.2 (22.1 to 41.1) |
Geometric mean of titers collected 14 days after the second vaccination.
| titer | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 |
|---|---|---|
| GMT of Saint Louis University's (SLU) PRNT Assay in Group A and Group B | 27.4 (19.1 to 39.3) | 212.2 (146.6 to 307.2) |
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
| Participants | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 | Group C: One Dose Dryvax, Day 0 | Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | Group E: IMVAMUNE + Dryvax, Day 0 | Group F: IMVAMUNE, Day 0 | Placebo A | Placebo B | Placebo D | Placebo E | Placebo F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Frequency of Serious Adverse Events (SAEs) | 1 | 2 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 |
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.
| Participants | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 | Group C: One Dose Dryvax, Day 0 | Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | Group E: IMVAMUNE + Dryvax, Day 0 | Group F: IMVAMUNE, Day 0 | Placebo A | Placebo B | Placebo D | Placebo E | Placebo F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Frequency of Non-Serious AEs | 32 | 43 | 4 | 1 | 0 | 26 | 4 | 2 | 0 | 0 | 5 |
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).
| Participants | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 | Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | Placebo A | Placebo B | Placebo D |
|---|---|---|---|---|---|---|
| Post First Vaccination | 47 | 50 | 4 | 1 | 2 | 0 |
| Post Second Vaccination | 51 | 53 | 3 | 0 | 0 | 1 |
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).
| Participants | Group C: One Dose Dryvax, Day 0 | Group F: IMVAMUNE, Day 0 | Placebo F |
|---|---|---|---|
| Frequency of Local Solicited Reactogenicity AEs for Groups C and F and Placebo F | 8 | 50 | 1 |
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).
| Participants | Group E: IMVAMUNE + Dryvax, Day 0 | Placebo E |
|---|---|---|
| MVA Vaccination | 1 | 0 |
| Dryvax Vaccination | 2 | 2 |
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).
| Participants | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 | Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | Placebo A | Placebo B | Placebo D |
|---|---|---|---|---|---|---|
| Post First Vaccination | 31 | 41 | 2 | 4 | 3 | 0 |
| Post Second Vaccination | 29 | 23 | 3 | 2 | 3 | 0 |
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).
| Participants | Group C: One Dose Dryvax, Day 0 | Group E: IMVAMUNE + Dryvax, Day 0 | Group F: IMVAMUNE, Day 0 | Placebo E | Placebo F |
|---|---|---|---|---|---|
| Frequency of Systemic Solicited Reactogenicity AEs for Groups C, E, and F and Placebo E and F | 5 | 2 | 33 | 1 | 3 |
Geometric mean of titers collected 14 days after the second vaccination.
| titer | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 |
|---|---|---|
| GMT of BN Enzyme Linked Immunosorbent Assay (ELISA) in Groups A and B | 108.7 (87.7 to 134.8) | 501.7 (364.1 to 691.3) |
Geometric mean of titers collected 14 days after the second vaccination.
| titer | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 |
|---|---|---|
| GMT of SLU ELISA in Groups A and B | 60.5 (51.0 to 71.7) | 510.9 (373.0 to 699.7) |
Collected over AEs collected include solicited AEs, unsolicited AEs, and SAEs. Solicited AEs were collected daily for 15 days post each vaccination. Unsolicited AEs were collected from the first vaccination through 28 days after the last vaccination. SAEs were collected from the first vaccination to study completion (Day 365 after the last vaccination).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group A: Two Doses IMVAMUNE, Days 0, 7 | 0/61 (0%) | 1/61 (1.6%) | 57/61 (93.4%) |
| Group B: Two Doses IMVAMUNE, Days 0, 28 | 0/67 (0%) | 2/67 (3%) | 66/67 (98.5%) |
| Group C: One Dose Dryvax, Day 0 | 0/8 (0%) | 0/8 (0%) | 8/8 (100%) |
| Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | 0/5 (0%) | 0/5 (0%) | 5/5 (100%) |
| Group E: IMVAMUNE + Dryvax, Day 0 | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| Group F: IMVAMUNE, Day 0 | 0/63 (0%) | 3/63 (4.8%) | 58/63 (92.1%) |
| Placebo A | 0/6 (0%) | 0/6 (0%) | 6/6 (100%) |
| Placebo B | 0/4 (0%) | 0/4 (0%) | 4/4 (100%) |
| Placebo D | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Placebo E | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| Placebo F | 0/7 (0%) | 0/7 (0%) | 6/7 (85.7%) |
| Event | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 | Group C: One Dose Dryvax, Day 0 | Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | Group E: IMVAMUNE + Dryvax, Day 0 | Group F: IMVAMUNE, Day 0 | Placebo A | Placebo B | Placebo D | Placebo E | Placebo F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| AppendicitisInfections and infestations | 1/61 | 0/67 | 0/8 | 0/5 | 0/2 | 0/63 | 0/6 | 0/4 | 0/1 | 0/2 | 0/7 |
| UrosepsisInfections and infestations | 0/61 | 0/67 | 0/8 | 0/5 | 0/2 | 1/63 | 0/6 | 0/4 | 0/1 | 0/2 | 0/7 |
| Adenocarcinoma of the cervixNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/61 | 0/67 | 0/8 | 0/5 | 0/2 | 1/63 | 0/6 | 0/4 | 0/1 | 0/2 | 0/7 |
| Ureteral disorderRenal and urinary disorders | 0/61 | 0/67 | 0/8 | 0/5 | 0/2 | 1/63 | 0/6 | 0/4 | 0/1 | 0/2 | 0/7 |
| Deep vein thrombosisVascular disorders | 0/61 | 0/67 | 0/8 | 0/5 | 0/2 | 1/63 | 0/6 | 0/4 | 0/1 | 0/2 | 0/7 |
| Complicated migraineNervous system disorders | 0/61 | 1/67 | 0/8 | 0/5 | 0/2 | 0/63 | 0/6 | 0/4 | 0/1 | 0/2 | 0/7 |
| Breast cosmetic surgerySurgical and medical procedures | 0/61 | 1/67 | 0/8 | 0/5 | 0/2 | 0/63 | 0/6 | 0/4 | 0/1 | 0/2 | 0/7 |
| Event | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 | Group C: One Dose Dryvax, Day 0 | Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | Group E: IMVAMUNE + Dryvax, Day 0 | Group F: IMVAMUNE, Day 0 | Placebo A | Placebo B | Placebo D | Placebo E | Placebo F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| FatigueGeneral disorders | 23/61 | 24/67 | 4/8 | 4/5 | 2/2 | 23/63 | 2/6 | 4/4 | 0/1 | 1/2 | 1/7 |
| Vaccination site erythemaGeneral disorders | 34/61 | 39/67 | 8/8 | 3/5 | 2/2 | 23/63 | 1/6 | 0/4 | 0/1 | 1/2 | 1/7 |
| Vaccination site painGeneral disorders | 52/61 | 59/67 | 5/8 | 4/5 | 1/2 | 45/63 | 0/6 | 2/4 | 0/1 | 2/2 | 1/7 |
| Vaccination site pruritusGeneral disorders | 18/61 | 15/67 | 7/8 | 2/5 | 2/2 | 11/63 | 0/6 | 0/4 | 1/1 | 2/2 | 0/7 |
| Vaccination site swellingGeneral disorders | 29/61 | 30/67 | 7/8 | 3/5 | 2/2 | 14/63 | 0/6 | 0/4 | 0/1 | 0/2 | 0/7 |
| MyalgiaMusculoskeletal and connective tissue disorders | 20/61 | 19/67 | 4/8 | 0/5 | 2/2 | 13/63 | 1/6 | 2/4 | 0/1 | 1/2 | 0/7 |
| HeadacheNervous system disorders | 21/61 | 30/67 | 2/8 | 1/5 | 2/2 | 24/63 | 2/6 | 2/4 | 0/1 | 1/2 | 2/7 |
| Axillary painGeneral disorders | 7/61 | 9/67 | 5/8 | 0/5 | 1/2 | 5/63 | 0/6 | 0/4 | 0/1 | 0/2 | 0/7 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 5/61 | 3/67 | 5/8 | 0/5 | 1/2 | 3/63 | 0/6 | 0/4 | 0/1 | 1/2 | 0/7 |
| ChillsGeneral disorders | 5/61 | 5/67 | 3/8 | 0/5 | 0/2 | 3/63 | 0/6 | 0/4 | 0/1 | 1/2 | 0/7 |
Participants were analyzed according to the treatment group they were randomized to.
| Age, Continuous(years) | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 | Group C: One Dose Dryvax, Day 0 | Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | Group E: IMVAMUNE + Dryvax, Day 0 | Group F: IMVAMUNE, Day 0 | Placebo A | Placebo B | Placebo D | Placebo E | Placebo F | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 24.7 ± 4.6 | 25.0 ± 3.9 | 26.5 ± 4.3 | 26.4 ± 5.1 | 31.0 ± 4.2 | 24.3 ± 3.9 | 25.2 ± 3.5 | 21.4 ± 2.3 | 24.0 ± NA | 20.5 ± 0.7 | 27.9 ± 4.8 | 24.8 ± 4.2 |
| Sex: Female, Male(Participants) | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 | Group C: One Dose Dryvax, Day 0 | Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | Group E: IMVAMUNE + Dryvax, Day 0 | Group F: IMVAMUNE, Day 0 | Placebo A | Placebo B | Placebo D | Placebo E | Placebo F | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | 25 | 36 | 1 | 2 | 1 | 32 | 3 | 0 | 0 | 0 | 5 | 105 |
| Male | 36 | 30 | 7 | 3 | 1 | 31 | 3 | 5 | 1 | 2 | 2 | 121 |
| Ethnicity (NIH/OMB)(Participants) | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 | Group C: One Dose Dryvax, Day 0 | Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | Group E: IMVAMUNE + Dryvax, Day 0 | Group F: IMVAMUNE, Day 0 | Placebo A | Placebo B | Placebo D | Placebo E | Placebo F | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 2 | 3 | 0 | 0 | 0 | 3 | 1 | 0 | 0 | 0 | 0 | 9 |
| Not Hispanic or Latino | 59 | 63 | 8 | 5 | 2 | 60 | 5 | 5 | 1 | 2 | 7 | 217 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Group A: Two Doses IMVAMUNE, Days 0, 7 | Group B: Two Doses IMVAMUNE, Days 0, 28 | Group C: One Dose Dryvax, Day 0 | Group D: IMVAMUNE, Day 0 + Dryvax, Day 7 | Group E: IMVAMUNE + Dryvax, Day 0 | Group F: IMVAMUNE, Day 0 | Placebo A | Placebo B | Placebo D | Placebo E | Placebo F | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 2 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 5 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 5 | 3 | 0 | 1 | 0 | 6 | 0 | 0 | 0 | 0 | 1 | 16 |
| White | 52 | 56 | 8 | 4 | 2 | 54 | 6 | 4 | 1 | 2 | 6 | 195 |
| More than one race | 4 | 3 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 8 |
| Unknown or Not Reported | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
This study is completed, as verified in Mar 2010. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: MVA-BN smallpox vaccine
National Institute of Allergy and Infectious Diseases (NIAID) →