A Phase 2 interventional study of MVA Smallpox Vaccine and MVA Smallpox Vaccine in Smallpox, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 8 sites in United States. Open to participants aged 18 Years to 38 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-02-03.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2, Interventional, and Prevention
Due to recent concern of biowarfare and bioterrorism, the US government is making efforts to improve its ability to protect citizens against the smallpox virus. This study will evaluate safety of IMVAMUNE®, an investigational smallpox vaccine, and its ability to stimulate the immune system (the body's defense system). Two vaccine preparations have the same name but one is a liquid and one is a powder that has liquid added just before it is given. The vaccine that comes as a liquid will be injected (given as a shot) just under the skin (subcutaneously) or injected between the layers of the skin (intradermally). The powder formulation is only injected just under the skin. Approximately 495 adults, age 18 older born after 1971, which have not had smallpox vaccine before, may participate in the study for about 7 months.
Smallpox was declared officially eradicated by the World Health Assembly in 1980. 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. Following the events of September 11, 2001 the Division of Microbiology and Infectious Diseases/National Institute of Allergy and Infectious Diseases contracted for the advanced development of IMVAMUNE®. Initially, a lyophilized formulation was manufactured, which was reconstituted 'at the bedside' prior to administration in clinical and non-clinical settings. Due in part to the potential requirement for mass vaccinations coupled with the increased manufacturing time and other constrains associated with lyophilization, it was decided to transition to a liquid product formulation. Therefore, after 2005, clinical and non-clinical efforts have focused largely on the liquid formulation, though non-clinical studies with the lyophilized formulation continued. Presently, due to the potential need to be able to stockpile Modified Vaccinia Ankara (MVA) for an extended period of time, there is renewed interest in the lyophilized formulation. The purpose of this study is to compare the safety and immunogenicity of lyophilized IMVAMUNE® [1x10\^8 tissue culture infectious dose 50 (TCID50)] versus liquid formulation IMVAMUNE® (1x10\^8 TCID50) administered by the subcutaneous (SC) route and a lower dose liquid formulation IMVAMUNE® (2x10\^7 TCID50) administered by the intradermal (ID) route in healthy vaccinia-naïve individuals. This study is designed as a randomized, non-placebo controlled, partially-blinded study (liquid versus lyophilized formulation by the SC route Group B versus A). The study staff is unblinded to Group C. The study will contain 3 arms: Group A [Number (N)=165] will receive a 2 dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL per dose) lyophilized formulation by the SC route on Day 0 and 28. Group B (N=165) will receive a 2 dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL per dose) liquid formulation by the SC route on Day 0 and 28. Group C (N=165) will receive a 2 dose regimen of IMVAMUNE® (2x10\^7 TCID50/0.1 mL per dose) liquid formulation by the ID route on Day 0 and 28. Safety will be measured by assessment of solicited local and systemic reactions within 15 days after each vaccination (Day 0-14), unsolicited adverse events for 28 days following the second vaccination (56 days following the initial vaccination for those subjects that fail to receive the second vaccination), and serious adverse events through six months post the final vaccination. Immunogenicity testing will include assessment of vaccinia-specific plaque reduction neutralizing antibody titers (PRNT) and enzyme linked immunosorbent assay (ELISA) mean geometric titers (GMT) based on individual peak titers. For each subject, the peak PRNT or ELISA will be defined as the largest titer among all available measurements post second vaccination.
73 studies on the registry are indexed under Smallpox; 5 are open to participants now.
This study's enrollment of 523 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.
Inclusion criteria that must be met prior to the initial vaccination:
If the subject is female and of childbearing potential, she agrees to use acceptable , and not become pregnant for 28 days following the last vaccination:
The following blood parameters:
Inclusion Criteria that must be met prior to the second 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:
Exclusion Criteria:
Exclusion criteria that apply prior to the initial vaccination:
Active disease
a. Persons with vitiligo or thyroid disease (e.g., taking thyroid hormone replacement) are not excluded
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 use for greater than 2 weeks duration within three months prior to vaccination and current use of medication
Exclusion criteria that apply prior to the second vaccination:
Active autoimmune disease
a. Persons with vitiligo or thyroid disease (e.g., taking thyroid hormone replacement) are not excluded
High-dose steroid use for greater than 2 weeks duration within three months prior to vaccination and current use of immunosuppressive medication.
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.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
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.
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.
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.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
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.
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.
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.
Group B: 165 subjects will receive a 2 dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL per dose) liquid formulation by the subcutaneous route on Day 0 and 28.
Biological: MVA Smallpox Vaccine
Group C: 165 subjects will receive a 2 dose regimen of IMVAMUNE® (2x10\^7 TCID50/0.1mL per dose) liquid formulation by the intradermal route on Day 0 and 28.
Biological: MVA Smallpox Vaccine
Group A: 165 subjects will receive a 2 dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL per dose) lyophilized formulation by the subcutaneous route on Day 0 and 28.
Biological: MVA Smallpox Vaccine
Vaccinia vaccine liquid formulation delivered by subcutaneous (SC) route at 1x10\^8 TCID50 per 0.5 mL dose on Days 0 and 28.
Vaccinia vaccine liquid formulation delivered at lower dose \[2x10\^7 tissue culture infectious dose 50 (TCID50) per 0.1 mL dose\] by intradermal (ID) route on Days 0 and 28.
Vaccinia vaccine lyophilized formulation delivered by subcutaneous (SC) route at 1x10\^8 TCID50 per 0.5 mL dose on Days 0 and 28.
Geometric Mean Titer (GMT) Based on Vaccinia-specific Individual Peak Plaque Reduction Neutralization Titers (PRNT) Following 2 Doses of IMVAMUNE® Lyophilized Versus Following 2 Doses of IMVAMUNE® Liquid Administered Subcutaneously, ITT Population
Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.
Time frame: Days 14, 28 and 180 after 2nd vaccination
GMT Based on Vaccinia-specific Individual Peak PRNT Following 2 Doses of IMVAMUNE® Lyophilized Versus Following 2 Doses of IMVAMUNE® Liquid Administered Subcutaneously, Per Protocol Population
Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.
Time frame: Days 14, 28 and 180 after 2nd vaccination
GMT Based on Vaccinia-specific Individual Peak PRNT, Following 2 (Lower) Doses Liquid IMVAMUNE® Administered Intradermally Versus 2 (Higher) Doses of Liquid IMVAMUNE® Administered Subcutaneously, ITT Population
Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.
Time frame: Days 14, 28 and 180 after 2nd vaccination
GMT Based on Vaccinia-specific Individual Peak PRNT, Following 2 (Lower) Doses Liquid IMVAMUNE® Administered Intradermally Versus 2 (Higher) Doses of Liquid IMVAMUNE® Administered Subcutaneously, Per Protocol Population
Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each timepoint as well as for the peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.
Time frame: Days 14, 28 and 180 after 2nd vaccination
Number of Participants Reporting Serious Adverse Events Associated With IMVAMUNE® Vaccination
An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Those SAEs considered associated are those with a known temporal relationship, or the event is known to occur in association with study product or with a product in a similar class of study products AND no alternate etiology is identified.
Time frame: Day 0 through 180 days after second vaccination
Number of Participants Assessed With Grade 3 and 4 Laboratory Toxicities Associated With IMVAMUNE®.
Safety laboratory parameters included hemoglobin, white blood cells (WBC), platelets, ALT, and serum creatinine. These parameters were evaluated at Day 0 and 14 days after vaccination. Thresholds for Grade 3 or 4 were hemoglobin less than 8.0 g/dL, WBC less than 2000 cells/mm\^3, platelets less than 50,000 cells/mm\^3, ALT 5.0 times the upper limit of normal (ULN) or greater, and serum creatinine of 1.9 times ULN or greater. Associated with IMVAMUNE was defined as a known temporal relationship, or the event is known to occur in association with study product or with a product in a similar class of study products AND no alternate etiology is identified.
Time frame: Days 0, 14 and 42
GMT Based on Vaccinia-specific Individual Peak ELISA Titers, Following 2 Doses (Lower) Liquid Formulation IMVAMUNE® Administered Intradermally Versus That Obtained Following 2 Doses IMVAMUNE® Liquid Formulation Administered Subcutaneously, ITT Population
Blood was collected from participants for testing in the ELISA assay with IMVAMUNE (non-replicating vaccinia in humans) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 25 (half the lower limit of detection) for analysis.
Time frame: Days 14, 28 and 180 after 2nd vaccination
GMT Based on Vaccinia-specific Individual Peak ELISA Titers, Following 2 Doses (Lower) Liquid Formulation IMVAMUNE® Administered Intradermally Versus That Obtained Following 2 Doses IMVAMUNE® Liquid Formulation Subcutaneously, Per Protocol Population
Blood was collected from participants for testing in the ELISA assay with IMVAMUNE (non-replicating vaccinia in humans) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 25 (half the lower limit of detection) for analysis.
Time frame: Days 14, 28 and 180 after second vaccination
GMT Based on Vaccinia-specific Individual Peak ELISA Titers Following 2 Doses of IMVAMUNE® Lyophilized Formulation Versus That Obtained Following 2 Doses of IMVAMUNE® Liquid Formulation Subcutaneously, ITT Population.
Blood was collected from participants for testing in the ELISA assay with IMVAMUNE (non-replicating vaccinia in humans) as the assay antigen. The geometric mean titers were calculated using the individual peak titer after second vaccination. Titer values below limit of detection were replaced by 25 (half the lower limit of detection) for analysis.
Time frame: Days 14, 28 and 180 after 2nd vaccination.
GMT Based on Vaccinia-specific Individual Peak ELISA Titers Following 2 Doses of IMVAMUNE® Lyophilized Formulation Versus That Obtained Following 2 Doses of IMVAMUNE® Liquid Formulation Subcutaneously, Per Protocol Population.
Blood was collected from participants for testing in the ELISA assay with IMVAMUNE (non-replicating vaccinia in humans) as the assay antigen. The geometric mean titers were calculated using the individual peak titer after second vaccination. Titer values below limit of detection were replaced by 25 (half the lower limit of detection) for analysis.
Time frame: Days 14, 28 and 180 after 2nd vaccination.
Participants were healthy adults age 18 and older (born after 1971) recruited from existing volunteer populations and from the communities at large around the clinical sites. Participants were enrolled between 09FEB2010 and 02SEP2010.
| Milestone | Lyophilized, Subcutaneous | Liquid, Subcutaneous | Liquid, Intradermal |
|---|---|---|---|
| Started | 165 | 167 | 191 |
| Received second vaccination | 150 | 157 | 153 |
| Completed | 155 | 160 | 180 |
| Not completed | 10 | 7 | 11 |
| Withdrew: Lost to follow-up | 6 | 7 | 9 |
| Withdrew: Withdrawal by subject | 3 | 0 | 2 |
| Withdrew: Adverse event | 1 | 0 | 0 |
Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.
| titer | Lyophilized, Subcutaneous | Liquid, Subcutaneous |
|---|---|---|
| Geometric Mean Titer (GMT) Based on Vaccinia-specific Individual Peak Plaque Reduction Neutralization Titers (PRNT) Following 2 Doses of IMVAMUNE® Lyophilized Versus Following 2 Doses of IMVAMUNE® Liquid Administered Subcutaneously, ITT Population | 77.9 (62.9 to 96.5) | 46.7 (37.9 to 57.4) |
Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.
| titer | Lyophilized, Subcutaneous | Liquid, Subcutaneous |
|---|---|---|
| GMT Based on Vaccinia-specific Individual Peak PRNT Following 2 Doses of IMVAMUNE® Lyophilized Versus Following 2 Doses of IMVAMUNE® Liquid Administered Subcutaneously, Per Protocol Population | 87.8 (71.2 to 108.3) | 49.5 (40.0 to 61.3) |
Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.
| titer | Liquid, Intradermal | Liquid, Subcutaneous |
|---|---|---|
| GMT Based on Vaccinia-specific Individual Peak PRNT, Following 2 (Lower) Doses Liquid IMVAMUNE® Administered Intradermally Versus 2 (Higher) Doses of Liquid IMVAMUNE® Administered Subcutaneously, ITT Population | 45.2 (37.0 to 55.4) | 46.7 (37.9 to 57.4) |
Blood was collected from participants for testing in the PRNT assay with vaccinia-Western Reserve (replicating vaccinia) as the assay antigen. The geometric mean titers were calculated for each timepoint as well as for the peak titer after second vaccination. Titer values below limit of detection were replaced by 7.5 (half the lower limit of detection) for analysis.
| titer | Liquid, Intradermal | Liquid, Subcutaneous |
|---|---|---|
| GMT Based on Vaccinia-specific Individual Peak PRNT, Following 2 (Lower) Doses Liquid IMVAMUNE® Administered Intradermally Versus 2 (Higher) Doses of Liquid IMVAMUNE® Administered Subcutaneously, Per Protocol Population | 59.6 (48.1 to 74.0) | 49.5 (40.0 to 61.3) |
An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Those SAEs considered associated are those with a known temporal relationship, or the event is known to occur in association with study product or with a product in a similar class of study products AND no alternate etiology is identified.
| participants | Lyophilized, Subcutaneous | Liquid, Subcutaneous | Liquid, Intradermal |
|---|---|---|---|
| Number of Participants Reporting Serious Adverse Events Associated With IMVAMUNE® Vaccination | 0 | 0 | 0 |
Safety laboratory parameters included hemoglobin, white blood cells (WBC), platelets, ALT, and serum creatinine. These parameters were evaluated at Day 0 and 14 days after vaccination. Thresholds for Grade 3 or 4 were hemoglobin less than 8.0 g/dL, WBC less than 2000 cells/mm\^3, platelets less than 50,000 cells/mm\^3, ALT 5.0 times the upper limit of normal (ULN) or greater, and serum creatinine of 1.9 times ULN or greater. Associated with IMVAMUNE was defined as a known temporal relationship, or the event is known to occur in association with study product or with a product in a similar class of study products AND no alternate etiology is identified.
| participants | Lyophilized, Subcutaneous | Liquid, Subcutaneous | Liquid, Intradermal |
|---|---|---|---|
| Number of Participants Assessed With Grade 3 and 4 Laboratory Toxicities Associated With IMVAMUNE®. | 0 | 0 | 0 |
Blood was collected from participants for testing in the ELISA assay with IMVAMUNE (non-replicating vaccinia in humans) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 25 (half the lower limit of detection) for analysis.
| titer | Liquid, Intradermal | Liquid, Subcutaneous |
|---|---|---|
| GMT Based on Vaccinia-specific Individual Peak ELISA Titers, Following 2 Doses (Lower) Liquid Formulation IMVAMUNE® Administered Intradermally Versus That Obtained Following 2 Doses IMVAMUNE® Liquid Formulation Administered Subcutaneously, ITT Population | 554.0 (474.2 to 647.1) | 700.5 (595.4 to 824.1) |
Blood was collected from participants for testing in the ELISA assay with IMVAMUNE (non-replicating vaccinia in humans) as the assay antigen. The geometric mean titers were calculated for each participant's individual peak titer after second vaccination. Titer values below limit of detection were replaced by 25 (half the lower limit of detection) for analysis.
| titer | Liquid, Intradermal | Liquid, Subcutaneous |
|---|---|---|
| GMT Based on Vaccinia-specific Individual Peak ELISA Titers, Following 2 Doses (Lower) Liquid Formulation IMVAMUNE® Administered Intradermally Versus That Obtained Following 2 Doses IMVAMUNE® Liquid Formulation Subcutaneously, Per Protocol Population | 757.9 (664.4 to 864.6) | 769.3 (661.8 to 894.2) |
Blood was collected from participants for testing in the ELISA assay with IMVAMUNE (non-replicating vaccinia in humans) as the assay antigen. The geometric mean titers were calculated using the individual peak titer after second vaccination. Titer values below limit of detection were replaced by 25 (half the lower limit of detection) for analysis.
| titer | Lyophilized, Subcutaneous | Liquid, Subcutaneous |
|---|---|---|
| GMT Based on Vaccinia-specific Individual Peak ELISA Titers Following 2 Doses of IMVAMUNE® Lyophilized Formulation Versus That Obtained Following 2 Doses of IMVAMUNE® Liquid Formulation Subcutaneously, ITT Population. | 893.5 (750.7 to 1063.5) | 700.5 (595.4 to 824.1) |
Blood was collected from participants for testing in the ELISA assay with IMVAMUNE (non-replicating vaccinia in humans) as the assay antigen. The geometric mean titers were calculated using the individual peak titer after second vaccination. Titer values below limit of detection were replaced by 25 (half the lower limit of detection) for analysis.
| titer | Lyophilized, Subcutaneous | Liquid, Subcutaneous |
|---|---|---|
| GMT Based on Vaccinia-specific Individual Peak ELISA Titers Following 2 Doses of IMVAMUNE® Lyophilized Formulation Versus That Obtained Following 2 Doses of IMVAMUNE® Liquid Formulation Subcutaneously, Per Protocol Population. | 1062.4 (920.8 to 1225.8) | 769.3 (661.8 to 894.2) |
Collected over Solicited reactogenicity symptoms were collected on memory aid for 15 days after each vaccination. Non-serious unsolicited adverse events were collected for 28 days after each vaccination. Serious adverse events were collected through 180 days after the second vaccination.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Lyophilized, Subcutaneous | 0/165 (0%) | 1/165 (0.6%) | 164/165 (99.4%) |
| Liquid, Subcutaneous | 0/167 (0%) | 2/167 (1.2%) | 161/167 (96.4%) |
| Liquid, Intradermal | 0/191 (0%) | 1/191 (0.5%) | 191/191 (100%) |
| Event | Lyophilized, Subcutaneous | Liquid, Subcutaneous | Liquid, Intradermal |
|---|---|---|---|
| Colitis ischaemicGastrointestinal disorders | 1/165 | 0/167 | 0/191 |
| AppendicitisInfections and infestations | 0/165 | 1/167 | 0/191 |
| ColitisGastrointestinal disorders | 0/165 | 1/167 | 0/191 |
| Back painMusculoskeletal and connective tissue disorders | 0/165 | 0/167 | 1/191 |
| Event | Lyophilized, Subcutaneous | Liquid, Subcutaneous | Liquid, Intradermal |
|---|---|---|---|
| Injection site erythemaGeneral disorders | 128/165 | 136/167 | 190/191 |
| Injection site swellingGeneral disorders | 108/165 | 116/167 | 190/191 |
| Injection site painGeneral disorders | 155/165 | 152/167 | 125/191 |
| Injection site pruritusGeneral disorders | 82/165 | 81/167 | 170/191 |
| Vaccination Site DiscolourationGeneral disorders | 16/165 | 7/167 | 122/191 |
| MalaiseGeneral disorders | 90/165 | 83/167 | 98/191 |
| HeadacheNervous system disorders | 83/165 | 72/167 | 79/191 |
| MyalgiaGeneral disorders | 81/165 | 69/167 | 58/191 |
| Vaccination Site NoduleGeneral disorders | 41/165 | 34/167 | 35/191 |
| NauseaGastrointestinal disorders | 40/165 | 36/167 | 44/191 |
| Age, Categorical(Participants) | Lyophilized, Subcutaneous | Liquid, Subcutaneous | Liquid, Intradermal | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 165 | 167 | 191 | 523 |
| >=65 years | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | Lyophilized, Subcutaneous | Liquid, Subcutaneous | Liquid, Intradermal | Total |
|---|---|---|---|---|
| Mean | 27.0 ± 4.4 | 26.8 ± 4.5 | 27.7 ± 4.9 | 27.2 ± 4.6 |
| Sex: Female, Male(Participants) | Lyophilized, Subcutaneous | Liquid, Subcutaneous | Liquid, Intradermal | Total |
|---|---|---|---|---|
| Female | 81 | 80 | 102 | 263 |
| Male | 84 | 87 | 89 | 260 |
| Ethnicity (NIH/OMB)(Participants) | Lyophilized, Subcutaneous | Liquid, Subcutaneous | Liquid, Intradermal | Total |
|---|---|---|---|---|
| Hispanic or Latino | 6 | 17 | 12 | 35 |
| Not Hispanic or Latino | 159 | 150 | 179 | 488 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Lyophilized, Subcutaneous | Liquid, Subcutaneous | Liquid, Intradermal | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 10 | 6 | 5 | 21 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 1 | 1 |
| Black or African American | 18 | 13 | 19 | 50 |
| White | 129 | 144 | 156 | 429 |
| More than one race | 8 | 3 | 8 | 19 |
| Unknown or Not Reported | 0 | 1 | 2 | 3 |
| Region of Enrollment(participants) | Lyophilized, Subcutaneous | Liquid, Subcutaneous | Liquid, Intradermal | Total |
|---|---|---|---|---|
| United States | 165 | 167 | 191 | 523 |
The record gives a start of Feb 2010, a primary completion of Apr 2011 and a completion of Apr 2011. It does not say whether these dates are actual or estimated.
Results were first posted in Jan 2021, 9 years 9 months after primary completion. A results delay was requested in Aug 2011.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jan 2011. 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) →