Smallpox
Conditions
Keywords
IMVAMUNE®, smallpox, vaccine
Brief 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. 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).
Interventions
BIOLOGICALMVA Smallpox Vaccine
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.
OTHERPlacebo
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).
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 38 Years
Healthy volunteers
Yes
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Systemic Solicited Reactogenicity AEs | 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). |
| Frequency of Local Solicited Reactogenicity AEs for Subjective Symptoms | 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 | 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. |
| Time to Seroconversion After One Vaccination Using Bavarian Nordic's (BN) Enzyme Linked Immunosorbent Assay (ELISA) in the Intent-to-Treat (ITT) Population | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Titer of SLU PRNT Assay After First Vaccination in the Per Protocol Population | Days 4, 8, 14, 21, and 28 after first vaccination | 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. |
| Peak Titer of Saint Louis University's (SLU) Plaque Reduction Neutralizing Antibody Titer (PRNT) Assay After First Vaccination in the ITT Population | Days 4, 8, 14, 21, and 28 after first vaccination | 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. |
Countries
United States
Participant flow
Recruitment details
The study population included vaccinia-naïve adults aged greater than 18 years (and born after 1971). Participants were recruited from two sites within the United States. The first participant was enrolled on May 29, 2009, and the last participant was enrolled on August 16, 2010.
Participants by arm
| Arm | Count |
|---|---|
| Group A: High Dose 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. | 45 |
| Group B: Standard Dose 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). | 45 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 1 |
Baseline characteristics
| Characteristic | Group B: Standard Dose | Total | Group A: High Dose |
|---|---|---|---|
| Age, Continuous | 26.8 years STANDARD_DEVIATION 4.8 | 26.8 years STANDARD_DEVIATION 4.7 | 26.9 years STANDARD_DEVIATION 4.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 84 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 39 Participants | 80 Participants | 41 Participants |
| Sex: Female, Male Female | 24 Participants | 48 Participants | 24 Participants |
| Sex: Female, Male Male | 21 Participants | 42 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 45 |
| other Total, other adverse events | 45 / 45 | 43 / 45 |
| serious Total, serious adverse events | 0 / 45 | 0 / 45 |
Outcome results
Primary
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.
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)
Population: The safety population includes all participants who received one dose of vaccine. One participant in Group A was additionally excluded due to receiving an incorrect dose for the first vaccination that did not correspond to either study group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: High Dose | Frequency of Local Solicited Reactogenicity AEs for Measured Symptoms | Post Vaccination 1 (Day 0 through Day 15) | 26 Participants |
| Group A: High Dose | Frequency of Local Solicited Reactogenicity AEs for Measured Symptoms | Post Vaccination 2 (Day 28 to Day 43) | 3 Participants |
| Group B: Standard Dose | Frequency of Local Solicited Reactogenicity AEs for Measured Symptoms | Post Vaccination 1 (Day 0 through Day 15) | 22 Participants |
| Group B: Standard Dose | Frequency of Local Solicited Reactogenicity AEs for Measured Symptoms | Post Vaccination 2 (Day 28 to Day 43) | 20 Participants |
Primary
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).
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)
Population: The safety population includes all participants who received one dose of vaccine. One participant in Group A was additionally excluded due to receiving an incorrect dose for the first vaccination that did not correspond to either study group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: High Dose | Frequency of Local Solicited Reactogenicity AEs for Subjective Symptoms | Post Vaccination 1 (Day 0 through Day 15) | 41 Participants |
| Group A: High Dose | Frequency of Local Solicited Reactogenicity AEs for Subjective Symptoms | Post Vaccination 2 (Day 28 through Day 43) | 7 Participants |
| Group B: Standard Dose | Frequency of Local Solicited Reactogenicity AEs for Subjective Symptoms | Post Vaccination 1 (Day 0 through Day 15) | 34 Participants |
| Group B: Standard Dose | Frequency of Local Solicited Reactogenicity AEs for Subjective Symptoms | Post Vaccination 2 (Day 28 through Day 43) | 33 Participants |
Primary
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.
Time frame: Day 0 after first vaccination to Day 28 after second vaccination (Day 56 after first vaccination)
Population: The safety population includes all participants who received one dose of vaccine. One participant in Group A was additionally excluded due to receiving an incorrect dose for the first vaccination that did not correspond to either study group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: High Dose | Frequency of Non-Serious AEs Related to Vaccination | 11 Participants |
| Group B: Standard Dose | Frequency of Non-Serious AEs Related to Vaccination | 9 Participants |
Primary
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
Time frame: Day 0 after first vaccination to study completion through Day 180 after second vaccination (Day 208 after first vaccination)
Population: The safety population includes all participants who received one dose of vaccine. One participant in Group A was additionally excluded due to receiving an incorrect dose for the first vaccination that did not correspond to either study group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: High Dose | Frequency of Serious Adverse Events (SAEs) Related to Vaccination | 0 Participants |
| Group B: Standard Dose | Frequency of Serious Adverse Events (SAEs) Related to Vaccination | 0 Participants |
Primary
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).
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)
Population: The safety population includes all participants who received one dose of vaccine. One participant in Group A was additionally excluded due to receiving an incorrect dose for the first vaccination that did not correspond to either study group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: High Dose | Frequency of Systemic Solicited Reactogenicity AEs | Post Vaccination 1 (Day 0 through Day 15) | 27 Participants |
| Group A: High Dose | Frequency of Systemic Solicited Reactogenicity AEs | Post Vaccination 2 (Day 28 to Day 43) | 7 Participants |
| Group B: Standard Dose | Frequency of Systemic Solicited Reactogenicity AEs | Post Vaccination 1 (Day 0 through Day 15) | 19 Participants |
| Group B: Standard Dose | Frequency of Systemic Solicited Reactogenicity AEs | Post Vaccination 2 (Day 28 to Day 43) | 11 Participants |
Primary
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.
Time frame: Days 0, 4, 8, 14, 21, and 28 after first vaccination
Population: The ITT population includes all participants enrolled and randomized. Participants in this population are analyzed according to the group they were randomized to.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: High Dose | Time to Seroconversion After One Vaccination Using Bavarian Nordic's (BN) Enzyme Linked Immunosorbent Assay (ELISA) in the Intent-to-Treat (ITT) Population | 14 days |
| Group B: Standard Dose | Time to Seroconversion After One Vaccination Using Bavarian Nordic's (BN) Enzyme Linked Immunosorbent Assay (ELISA) in the Intent-to-Treat (ITT) Population | 14 days |
Comparison: Null hypothesis: Median time to seroconversion among participants receiving one standard dose in Group B is 2.5-fold higher compared to participants receiving one high dose in Group A (hazard ratio = 2.5).95% CI: [0.398, 0.868]
Primary
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.
Time frame: Days 0, 4, 8, 14, 21, and 28 after first vaccination
Population: The per protocol population includes all participants who received one dose of vaccine and contributed both pre- and post-vaccination blood samples for testing for which valid results were reported. One participant in Group A was additionally excluded due to receiving an incorrect dose for the first vaccination that did not correspond to either study group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: High Dose | Time to Seroconversion After One Vaccination Using BN ELISA in the Per Protocol Population | 14 days |
| Group B: Standard Dose | Time to Seroconversion After One Vaccination Using BN ELISA in the Per Protocol Population | 14 days |
Comparison: Null hypothesis: Median time to seroconversion among participants receiving one standard dose in Group B is 2.5-fold higher compared to participants receiving one high dose in Group A (hazard ratio = 2.5).95% CI: [0.384, 0.853]
Secondary
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.
Time frame: Days 4, 8, 14, 21, and 28 after first vaccination
Population: The ITT population includes all participants enrolled and randomized. Participants in this population are analyzed according to the group they were randomized to.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: High Dose | Peak Titer of Saint Louis University's (SLU) Plaque Reduction Neutralizing Antibody Titer (PRNT) Assay After First Vaccination in the ITT Population | 4.94 log2.5 of titer | Standard Error 0.19 |
| Group B: Standard Dose | Peak Titer of Saint Louis University's (SLU) Plaque Reduction Neutralizing Antibody Titer (PRNT) Assay After First Vaccination in the ITT Population | 4.56 log2.5 of titer | Standard Error 0.23 |
Comparison: Null hypothesis: The mean difference in log2.5 transformed peak titers between Group A and Group B \>= 1.95% CI: [-0.2, 0.97]
Secondary
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.
Time frame: Days 4, 8, 14, 21, and 28 after first vaccination
Population: The ITT population includes all participants enrolled and randomized. Participants in this population are analyzed according to the group they were randomized to.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: High Dose | Peak Titer of SLU PRNT Assay After First Vaccination in the Per Protocol Population | 4.98 log2.5 of titer | Standard Error 0.19 |
| Group B: Standard Dose | Peak Titer of SLU PRNT Assay After First Vaccination in the Per Protocol Population | 4.56 log2.5 of titer | Standard Error 0.23 |
Comparison: Null hypothesis: The mean difference in log2.5 transformed peak titers between Group A and Group B \>= 1.95% CI: [-0.17, 1]