Influenza
Conditions
Keywords
influenza, H5N1, vaccine, avian influenza, parent protocol
Brief summary
Severe disease in humans due to bird influenza viruses (H5N1) has led to concern that this virus may result in a widespread outbreak of bird flu. The purpose of this study is to evaluate the dose and dosing schedule for 2 different types of H5N1 vaccine. Participants will be randomly assigned to 1 of 9 possible vaccine groups. All participants will receive 2 doses of Clade 1, Clade 2, or combination Clade 1 and 2 on Day 0. All participants will receive a second dose of the same vaccine or a different vaccine type on study day 7, 14, 28 or 180. Study participants will include about 500 healthy adult subjects, ages 18-49 years old, who have no history of prior H5 flu exposure or vaccination. Study procedures may include medical history, physical exam, and blood sampling. Subject participation may last up to 372 days. Several DMID studies have recently evaluated H5N1 vaccines in healthy adults, 04-063, 05-0090, 05-0015, and 05-0043.
Detailed description
Severe disease in humans due to avian influenza viruses of the H5N1 subtype has raised concern regarding the potential emergence of these viruses in pandemic form. Results of earlier studies suggest that previous priming can significantly affect the responses to subsequent booster doses, even if these booster doses represent an antigenic variant. Both the length of time between priming and revaccination, as well as the antigenic relatedness of the priming and revaccination antigens, may impact the response. These issues could have an important impact on pre-vaccination strategies prior to the emergence of a pandemic. This study will evaluate immunogenicity with the same or with different H5 variants. In this study, different will be defined as clade 1 followed by clade 1, clade 1 followed by clade 2, clade 2 followed by clade 2, or a combination of clades 1 & 2 followed by a combination of clades 1 & 2. In addition, the study will evaluate the effect of the interval between doses on the subsequent response, with ultra-short intervals defined as 7 or 14 days, a short interval defined as 28 days and a long interval defined as 180 days. The study will evaluate whether the use of a longer duration between doses or cross-clade priming will result in enhanced immunogenicity. Primary objectives are: evaluate the dose and schedules of unadjuvanted inactivated subvirion H5N1 vaccines belonging to the same or different clades in H5-naïve, healthy adults; determine if boosting of subjects given the inactivated influenza rg A/Vietnam/1203/04 vaccine with a heterologous antigen inactivated influenza rg A/Indonesia/05/05 results in broader or higher immune responses compared with boosting with the homologous antigen; and evaluate the immune response to 2 doses of H5 vaccine given at times \< 1 month apart. Secondary objectives are: determine the safety of 2 doses of inactivated H5 vaccines in healthy adults given at different schedules and antigen combinations; obtain additional information regarding the antibody response to a single dose and to ultra-short immunization schedules; and evaluate the effect on antibody levels after receiving an antigenic variant to the priming virus given as a booster or simultaneously. The study will be conducted as a randomized, prospective controlled, multi-center trial. Approximately 500 healthy adult subjects, aged 18-49, who have no history of prior H5 influenza exposure or vaccination will be enrolled. Subjects will be randomized to receive varying schedules, (2 doses separated by 7, 14, 28 or 180 days), and clades of unadjuvanted inactivated subvirion H5N1 vaccine.
Interventions
BIOLOGICALA/Vietnam/1203/04
Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.
BIOLOGICALA/Indonesia/05/05
Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.
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 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women, 18 through 49 years old, who deny exposure to H5 virus or participation in an H5 vaccine study. * In good health, as determined by vital signs (heart rate less than 100 bpm; blood pressure: systolic less than or equal to 140 mm Hg; diastolic less than or equal to 90 mm Hg; oral temperature less than 100.0 degrees Fahrenheit), medical history to ensure stable medical condition and a targeted physical examination, as indicated, based on medical history. A stable medical condition is defined as no recent change in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months. Any change that is due to change of health care provider, insurance company, etc, or is done for financial reasons, as long as in the same class of medication, will not be considered a violation of the inclusion criterion. Any change to prescription medication due to improvement of a disease outcome will not be considered a violation of the inclusion criterion. * Women of childbearing potential (not surgically sterile or postmenopausal for greater than or equal to 1 year) must not be pregnant as indicated by a negative pregnancy test (urine or serum) within 24 hours prior to vaccine administration. * Women of childbearing potential who are at risk of becoming pregnant must agree to practice adequate contraception (i.e., barrier methods, abstinence, monogamous relationship with vasectomized partner, intrauterine devices, Depo-Provera, Norplant, oral contraceptives, contraceptive patches or other licensed, effective methods) until 30 days following receipt of the last dose of vaccine. * Able to understand and comply with planned study procedures. * Able to provide informed consent prior to initiation of any study procedures and be available for all study visits.
Exclusion criteria
* Has occupational exposure to poultry, to include but is not limited to chicken, turkey, or duck farmer, factory worker in poultry processing plant, veterinary staff that handles poultry; has recreational exposure to poultry, e.g. raising poultry in 4-H club, duck hunter that slaughters/handles the kill or history of previous H5N1 vaccination or exposure. * Has a known allergy to eggs, egg products or other components of the vaccine (including gelatin, formaldehyde, octoxinol, thimerosal and egg or chicken protein). * Is female of child-bearing potential who is breastfeeding or intends to become pregnant during the study period up to 30 days following receipt of the last dose of vaccine. * Has immunosuppression as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months. * Has an active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematologic malignancy. Active neoplastic disease is defined as no neoplastic disease or treatment for neoplastic disease within the past 5 years. * Has long-term use (greater than 2 weeks) of oral or parenteral steroids (glucocorticoids), or high-dose inhaled steroids (\>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids are allowed). * Has a history of receiving immunoglobulin or other blood products within the 3 months prior to enrollment in this study. * Has received any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study, or plans to receive any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) following each study vaccine. * Has an acute or chronic medical condition that would render vaccination unsafe or would interfere with the evaluation of responses. This includes, but is not limited to solicited reactogenicity symptoms, known chronic liver disease, significant renal disease, unstable or progressive neurological disorders, diabetes mellitus, and transplant recipients. * Has a history of severe reactions following vaccination with contemporary influenza virus vaccines. * Has an acute illness or has an oral temperature greater than 99.9 degrees Fahrenheit (37.7 degrees Celsius) within 3 days prior to enrollment. * Has received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to enrollment in this study, or expects to receive an experimental agent during the study period. * Has any condition that would, in the opinion of the site principal investigator place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol. * Has a diagnosis of schizophrenia, bipolar disease or other severe (disabling) chronic psychiatric diagnosis. * Has been hospitalized for psychiatric illness, history of suicide attempt or confinement for danger to self or others. * Is receiving psychiatric drugs. Subjects who are receiving a single antidepressant drug and are stable for at least 3 months prior to enrollment without decompensating are allowed enrollment into the study. * Has known human immunodeficiency virus, hepatitis B, or hepatitis C infection. * Has a history of alcohol or drug abuse in the 5 years prior to enrollment. * Has a history of Guillain-Barré syndrome. * Has any condition that the investigator believes may interfere with successful completion of the study. * Plans to enroll in another clinical trial (that has a study intervention in the form of drug, biologic or device that could interfere with safety assessment of H5N1 vaccine) at any time during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 28 days post last vaccination. | The GMTs are as assessed by the HAI assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. |
| Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 28 days post last vaccination. | The GMTs are as assessed by the HAI assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. |
| Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen | 28 days post last vaccination. | The number of subjects who achieve a 4-fold or greater rise in titer, relative to the baseline (Day 0) titer, assessed by the HAI assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. Subjects whose baseline titer is \<10 must have a post vaccination titer of at least 1:40 to be considered a 4-fold rise. |
| Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen | 28 days post last vaccination. | The number of subjects who achieve a 4-fold or greater rise in titer, relative to the baseline (Day 0) titer, assessed by the HAI assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. Subjects whose baseline titer is \<10 must have a post vaccination titer of at least 1:40 to be considered a 4-fold rise. |
| Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 28 days post last vaccination. | The number of subjects who achieve a HAI antibody titer of 1:40 or greater as assessed by the HAI assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. |
| Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 28 days post last vaccination. | The number of subjects who achieve a HAI antibody titer of 1:40 or greater as assessed by the HAI assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen | 28 days post last vaccination. | The number of subjects who achieve a 4-fold or greater rise in titer, relative to the baseline (Day 0) titer, assessed by the microneutralization assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. Subjects whose baseline titer is \<10 must have a post vaccination titer of at least 1:40 to be considered a 4-fold rise. |
| Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 28 days post last vaccination. | The number of subjects who achieve a titer of 1:40 or greater as assessed by the microneutralization assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. |
| Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 28 days post last vaccination. | The number of subjects who achieve a titer of 1:40 or greater as assessed by the microneutralization assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. |
| Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | Six months post last vaccination | The GMTs are as assessed by the HAI assay against the A/Vietnam/04 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. |
| Number of Serious Adverse Events | Duration of study | Serious adverse events were collected at each study visit from the time of first vaccination through the final study visit at 180 days after the last vaccination. |
| Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | Six months post last vaccination | The GMTs are as assessed by the microneutralization assay against the A/Vietnam/04 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. |
| Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | Six months post last vaccination | The GMTs are as assessed by the microneutralization assay against the A/Indonesia/05 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. |
| Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Weeks 1, 2, 3 and 4 after the second dose | The kinetics of the antibody response to vaccination with A/Vietnam/04 is evaluated by the HAI GMT against the A/Vietnam/04 antigen at weekly intervals after receipt of 2 doses 7, 14 and 28 days apart |
| Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | Six months after last vaccination | The GMTs are as assessed by the HAI assay against the A/Indonesia/05 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. The CI shown as 5.0 to 5.0 reflect that all subjects had a titer of 5.0 for the VN,VN, Day 0,14 and VN, Day 0 groups. |
| Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | 7 days after first vaccination | Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after first vaccination and review the Memory Aid with clinic staff at follow a up visit on Day 8. Subjects are counted if they indicated experiencing the symptom at any severity during the reporting period. The symptoms of redness and swelling were solicited as both functional grading as impact on daily activies as well as collected as a measured value in mm. The number reported for all symptoms is the number reporting greater than none. |
| Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | 7 days after second vaccination | Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after the second vaccination and review the Memory Aid with clinic staff at a follow up visit on Day 8. Subjects are counted if they indicated experiencing the symptom at any severity during the reporting period. The symptoms of redness and swelling were solicited as both functional grading as impact on daily activies as well as collected as a measured value in mm. The number reported for all symptoms is the number reporting greater than none. |
| Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 28 days post last vaccination. | The GMTs are as assessed by the microneutralization assay against the A/Vietnam/04 antigen at 1 month following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. |
| Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 28 days post last vaccination. | The GMTs are as assessed by the microneutralization assay against the A/Indonesia/05 antigen at 1 month following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. |
| Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen | 28 days post last vaccination. | The number of subjects who achieve a 4-fold or greater rise in titer, relative to the baseline (Day 0) titer, assessed by the microneutralization assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. Subjects whose baseline titer is \<10 must have a post vaccination titer of at least 1:40 to be considered a 4-fold rise. |
Countries
United States
Participant flow
Recruitment details
Healthy ambulatory adults were recruited from the surrounding communities of the research clinics from September 8, 2008 to November 12, 2008.
Participants by arm
| Arm | Count |
|---|---|
| VN/VN, Day 0, 7 Day 0, Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine (VN); 90 mcg dosage; Day 7, Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine (VN); 90 mcg dosage. | 27 |
| VN/VN, Day 0, 14 Day 0, Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine (VN); 90 mcg dosage; Day 14, Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine (VN); 90 mcg dosage. | 26 |
| I/I, Day 0, 28 Day 0, Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine (I); 90 mcg dosage; Day 28, Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine (I); 90 mcg dosage. | 51 |
| VN/I, Day 0, 28 Day 0, Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine (VN); 90 mcg dosage; Day 28, Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine (I); 90 mcg dosage. | 49 |
| VN+I/VN+I, Day 0, 28 Day 0, Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine (VN); 45 mcg dosage and Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine (I); 45 mcg dosage; Day 28, Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine (VN); 45 mcg dosage and Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine (I); 45 mcg dosage. | 51 |
| VN/I, Day 0, 180 Day 0, Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine (VN); 90 mcg dosage; Day 180, Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine (I); 90 mcg dosage. | 49 |
| I/I, Day 0, 180 Day 0, Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine (I); 90 mcg dosage; Day 180, Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine (I); 90 mcg dosage. | 52 |
| VN, Day 0 Day 0, Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine (VN); 90 mcg dosage. | 97 |
| VN/VN, Day 0, 28 Day 0, Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine (VN); 90 mcg dosage; Day 28, Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine (VN); 90 mcg dosage. | 103 |
| Total | 505 |
Baseline characteristics
| Characteristic | VN/VN, Day 0, 14 | I/I, Day 0, 28 | VN/I, Day 0, 28 | VN+I/VN+I, Day 0, 28 | VN/I, Day 0, 180 | VN/VN, Day 0, 7 | I/I, Day 0, 180 | VN, Day 0 | VN/VN, Day 0, 28 | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 51 Participants | 49 Participants | 51 Participants | 49 Participants | 27 Participants | 52 Participants | 97 Participants | 103 Participants | 505 Participants |
| Age Continuous | 34.0 years STANDARD_DEVIATION 9.5 | 37.0 years STANDARD_DEVIATION 9.2 | 33.6 years STANDARD_DEVIATION 7.9 | 31.9 years STANDARD_DEVIATION 8.8 | 33.8 years STANDARD_DEVIATION 9.3 | 34.6 years STANDARD_DEVIATION 9.6 | 33.5 years STANDARD_DEVIATION 9.6 | 34.3 years STANDARD_DEVIATION 9.4 | 35.2 years STANDARD_DEVIATION 8.4 | 34.3 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 26 participants | 51 participants | 49 participants | 51 participants | 49 participants | 27 participants | 52 participants | 97 participants | 103 participants | 505 participants |
| Sex: Female, Male Female | 14 Participants | 36 Participants | 31 Participants | 24 Participants | 26 Participants | 14 Participants | 30 Participants | 60 Participants | 61 Participants | 296 Participants |
| Sex: Female, Male Male | 12 Participants | 15 Participants | 18 Participants | 27 Participants | 23 Participants | 13 Participants | 22 Participants | 37 Participants | 42 Participants | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 26 | 23 / 25 | 44 / 51 | 42 / 48 | 42 / 51 | 46 / 49 | 39 / 52 | 85 / 97 | 98 / 103 |
| serious Total, serious adverse events | 0 / 26 | 1 / 25 | 0 / 51 | 0 / 48 | 0 / 51 | 0 / 49 | 1 / 52 | 0 / 97 | 0 / 103 |
Outcome results
Primary
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen
The GMTs are as assessed by the HAI assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VN/VN, Day 0, 7 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 5.1 Titer |
| VN/VN, Day 0, 14 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 5.1 Titer |
| I/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 27.6 Titer |
| VN/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 10.1 Titer |
| VN+I/VN+I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 24.3 Titer |
| VN/I, Day 0, 180 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 41.3 Titer |
| I/I, Day 0, 180 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 58.7 Titer |
| VN, Day 0 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 5.3 Titer |
| VN/VN, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 5.7 Titer |
Primary
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen
The GMTs are as assessed by the HAI assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VN/VN, Day 0, 7 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 14.7 Titer |
| VN/VN, Day 0, 14 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 27.9 Titer |
| I/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 6.7 Titer |
| VN/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 13.6 Titer |
| VN+I/VN+I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 15.1 Titer |
| VN/I, Day 0, 180 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 39.7 Titer |
| I/I, Day 0, 180 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 10.5 Titer |
| VN, Day 0 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 9.1 Titer |
| VN/VN, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 22.9 Titer |
Primary
Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen
The number of subjects who achieve a 4-fold or greater rise in titer, relative to the baseline (Day 0) titer, assessed by the HAI assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. Subjects whose baseline titer is \<10 must have a post vaccination titer of at least 1:40 to be considered a 4-fold rise.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VN/VN, Day 0, 7 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen | 0 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen | 0 Participants |
| I/I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen | 23 Participants |
| VN/I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen | 9 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen | 22 Participants |
| VN/I, Day 0, 180 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen | 24 Participants |
| I/I, Day 0, 180 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen | 32 Participants |
| VN, Day 0 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen | 1 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen | 3 Participants |
Primary
Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen
The number of subjects who achieve a 4-fold or greater rise in titer, relative to the baseline (Day 0) titer, assessed by the HAI assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. Subjects whose baseline titer is \<10 must have a post vaccination titer of at least 1:40 to be considered a 4-fold rise.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VN/VN, Day 0, 7 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen | 8 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen | 10 Participants |
| I/I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen | 3 Participants |
| VN/I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen | 11 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen | 14 Participants |
| VN/I, Day 0, 180 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen | 25 Participants |
| I/I, Day 0, 180 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen | 8 Participants |
| VN, Day 0 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen | 14 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen | 41 Participants |
Primary
Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen
The number of subjects who achieve a HAI antibody titer of 1:40 or greater as assessed by the HAI assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VN/VN, Day 0, 7 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 0 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 0 Participants |
| I/I, Day 0, 28 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 23 Participants |
| VN/I, Day 0, 28 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 9 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 22 Participants |
| VN/I, Day 0, 180 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 24 Participants |
| I/I, Day 0, 180 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 32 Participants |
| VN, Day 0 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 1 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 3 Participants |
Primary
Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen
The number of subjects who achieve a HAI antibody titer of 1:40 or greater as assessed by the HAI assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VN/VN, Day 0, 7 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 8 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 10 Participants |
| I/I, Day 0, 28 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 3 Participants |
| VN/I, Day 0, 28 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 11 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 14 Participants |
| VN/I, Day 0, 180 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 25 Participants |
| I/I, Day 0, 180 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 8 Participants |
| VN, Day 0 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 14 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 41 Participants |
Secondary
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination
The GMTs are as assessed by the HAI assay against the A/Indonesia/05 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. The CI shown as 5.0 to 5.0 reflect that all subjects had a titer of 5.0 for the VN,VN, Day 0,14 and VN, Day 0 groups.
Time frame: Six months after last vaccination
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VN/VN, Day 0, 7 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 5.4 Titer |
| VN/VN, Day 0, 14 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 5.0 Titer |
| I/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 7.8 Titer |
| VN/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 6.4 Titer |
| VN+I/VN+I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 6.2 Titer |
| VN/I, Day 0, 180 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 6.7 Titer |
| I/I, Day 0, 180 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 8.4 Titer |
| VN, Day 0 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 5.0 Titer |
| VN/VN, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 5.2 Titer |
Secondary
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses
The kinetics of the antibody response to vaccination with A/Vietnam/04 is evaluated by the HAI GMT against the A/Vietnam/04 antigen at weekly intervals after receipt of 2 doses 7, 14 and 28 days apart
Time frame: Weeks 1, 2, 3 and 4 after the second dose
Population: Analyses are based on a modified intent to treat population. 5 subjects in the VN/VN, Day 0, 28 group not receiving vaccination 2 are excluded, as were 2, also in this group, due to receipt of prohibited vaccines.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| VN/VN, Day 0, 7 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 1 | 16.2 Titer |
| VN/VN, Day 0, 7 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 2 | 18.5 Titer |
| VN/VN, Day 0, 7 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 3 | 16.2 Titer |
| VN/VN, Day 0, 7 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 4 | 14.7 Titer |
| VN/VN, Day 0, 14 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 4 | 27.9 Titer |
| VN/VN, Day 0, 14 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 1 | 33.2 Titer |
| VN/VN, Day 0, 14 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 3 | 28.7 Titer |
| VN/VN, Day 0, 14 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 2 | 32.4 Titer |
| I/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 4 | 22.9 Titer |
| I/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 2 | 29.9 Titer |
| I/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 3 | 30.9 Titer |
| I/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses | Week 1 | 23.5 Titer |
Secondary
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination
The GMTs are as assessed by the HAI assay against the A/Vietnam/04 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Time frame: Six months post last vaccination
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VN/VN, Day 0, 7 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 8.8 Titer |
| VN/VN, Day 0, 14 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 9.0 Titer |
| I/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 6.1 Titer |
| VN/I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 6.6 Titer |
| VN+I/VN+I, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 7.7 Titer |
| VN/I, Day 0, 180 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 8.3 Titer |
| I/I, Day 0, 180 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 5.5 Titer |
| VN, Day 0 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 7.3 Titer |
| VN/VN, Day 0, 28 | Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 10.4 Titer |
Secondary
Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen
The GMTs are as assessed by the microneutralization assay against the A/Indonesia/05 antigen at 1 month following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VN/VN, Day 0, 7 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 5.3 Titer |
| VN/VN, Day 0, 14 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 6.1 Titer |
| I/I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 70.0 Titer |
| VN/I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 21.5 Titer |
| VN+I/VN+I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 66.8 Titer |
| VN/I, Day 0, 180 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 85.3 Titer |
| I/I, Day 0, 180 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 183.2 Titer |
| VN, Day 0 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 5.4 Titer |
| VN/VN, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen | 7.2 Titer |
Secondary
Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination
The GMTs are as assessed by the microneutralization assay against the A/Indonesia/05 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Time frame: Six months post last vaccination
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VN/VN, Day 0, 7 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 5.5 Titer |
| VN/VN, Day 0, 14 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 6.0 Titer |
| I/I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 20.6 Titer |
| VN/I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 16.1 Titer |
| VN+I/VN+I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 18.4 Titer |
| VN/I, Day 0, 180 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 14.7 Titer |
| I/I, Day 0, 180 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 23.0 Titer |
| VN, Day 0 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 5.5 Titer |
| VN/VN, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination | 5.9 Titer |
Secondary
Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen
The GMTs are as assessed by the microneutralization assay against the A/Vietnam/04 antigen at 1 month following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VN/VN, Day 0, 7 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 9.1 Titer |
| VN/VN, Day 0, 14 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 12.6 Titer |
| I/I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 5.8 Titer |
| VN/I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 9.8 Titer |
| VN+I/VN+I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 9.6 Titer |
| VN/I, Day 0, 180 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 56.6 Titer |
| I/I, Day 0, 180 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 10.9 Titer |
| VN, Day 0 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 7.1 Titer |
| VN/VN, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen | 17.0 Titer |
Secondary
Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination
The GMTs are as assessed by the microneutralization assay against the A/Vietnam/04 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Time frame: Six months post last vaccination
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| VN/VN, Day 0, 7 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 5.8 Titer |
| VN/VN, Day 0, 14 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 8.3 Titer |
| I/I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 5.3 Titer |
| VN/I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 6.2 Titer |
| VN+I/VN+I, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 6.4 Titer |
| VN/I, Day 0, 180 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 7.7 Titer |
| I/I, Day 0, 180 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 5.2 Titer |
| VN, Day 0 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 5.8 Titer |
| VN/VN, Day 0, 28 | Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination | 8.5 Titer |
Secondary
Number of Serious Adverse Events
Serious adverse events were collected at each study visit from the time of first vaccination through the final study visit at 180 days after the last vaccination.
Time frame: Duration of study
Population: All subjects receiving at least one study vaccination are included in the safety population and analyses of safety are intention to treat (ITT). Three subjects were randomized but not vaccinated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VN/VN, Day 0, 7 | Number of Serious Adverse Events | 0 Events |
| VN/VN, Day 0, 14 | Number of Serious Adverse Events | 1 Events |
| I/I, Day 0, 28 | Number of Serious Adverse Events | 0 Events |
| VN/I, Day 0, 28 | Number of Serious Adverse Events | 0 Events |
| VN+I/VN+I, Day 0, 28 | Number of Serious Adverse Events | 0 Events |
| VN/I, Day 0, 180 | Number of Serious Adverse Events | 0 Events |
| I/I, Day 0, 180 | Number of Serious Adverse Events | 1 Events |
| VN, Day 0 | Number of Serious Adverse Events | 0 Events |
| VN/VN, Day 0, 28 | Number of Serious Adverse Events | 0 Events |
Secondary
Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen
The number of subjects who achieve a 4-fold or greater rise in titer, relative to the baseline (Day 0) titer, assessed by the microneutralization assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. Subjects whose baseline titer is \<10 must have a post vaccination titer of at least 1:40 to be considered a 4-fold rise.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VN/VN, Day 0, 7 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen | 0 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen | 0 Participants |
| I/I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen | 34 Participants |
| VN/I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen | 14 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen | 34 Participants |
| VN/I, Day 0, 180 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen | 30 Participants |
| I/I, Day 0, 180 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen | 43 Participants |
| VN, Day 0 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen | 1 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen | 1 Participants |
Secondary
Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen
The number of subjects who achieve a 4-fold or greater rise in titer, relative to the baseline (Day 0) titer, assessed by the microneutralization assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. Subjects whose baseline titer is \<10 must have a post vaccination titer of at least 1:40 to be considered a 4-fold rise.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VN/VN, Day 0, 7 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen | 3 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen | 6 Participants |
| I/I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen | 1 Participants |
| VN/I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen | 7 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen | 3 Participants |
| VN/I, Day 0, 180 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen | 28 Participants |
| I/I, Day 0, 180 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen | 6 Participants |
| VN, Day 0 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen | 7 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen | 30 Participants |
Secondary
Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen
The number of subjects who achieve a titer of 1:40 or greater as assessed by the microneutralization assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VN/VN, Day 0, 7 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 0 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 0 Participants |
| I/I, Day 0, 28 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 34 Participants |
| VN/I, Day 0, 28 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 14 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 34 Participants |
| VN/I, Day 0, 180 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 30 Participants |
| I/I, Day 0, 180 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 43 Participants |
| VN, Day 0 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 1 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen | 1 Participants |
Secondary
Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen
The number of subjects who achieve a titer of 1:40 or greater as assessed by the microneutralization assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Time frame: 28 days post last vaccination.
Population: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VN/VN, Day 0, 7 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 3 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 6 Participants |
| I/I, Day 0, 28 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 1 Participants |
| VN/I, Day 0, 28 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 7 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 3 Participants |
| VN/I, Day 0, 180 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 28 Participants |
| I/I, Day 0, 180 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 6 Participants |
| VN, Day 0 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 7 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen | 30 Participants |
Secondary
Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after first vaccination and review the Memory Aid with clinic staff at follow a up visit on Day 8. Subjects are counted if they indicated experiencing the symptom at any severity during the reporting period. The symptoms of redness and swelling were solicited as both functional grading as impact on daily activies as well as collected as a measured value in mm. The number reported for all symptoms is the number reporting greater than none.
Time frame: 7 days after first vaccination
Population: All subjects receiving the first vaccination are included in the safety population and analyses of safety are ITT. Three subjects were randomized but not vaccinated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Myalgia | 5 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Fever | 1 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Tenderness | 17 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (measured) | 1 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Malaise | 2 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Pain | 9 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (functional) | 3 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Nausea | 2 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (functional) | 0 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (measured) | 3 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Headache | 5 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Malaise | 4 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Myalgia | 8 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (measured) | 6 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (functional) | 6 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Pain | 11 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (measured) | 4 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Fever | 1 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Headache | 11 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (functional) | 3 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Nausea | 1 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Tenderness | 15 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Tenderness | 21 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Malaise | 10 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (measured) | 4 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Myalgia | 13 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Pain | 10 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Fever | 2 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (functional) | 6 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Headache | 19 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Nausea | 2 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (measured) | 12 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (functional) | 3 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Headache | 18 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (measured) | 3 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Fever | 3 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Malaise | 13 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (functional) | 2 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Myalgia | 12 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (measured) | 9 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (functional) | 7 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Tenderness | 35 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Nausea | 5 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Pain | 14 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (functional) | 10 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Myalgia | 13 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Fever | 4 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (measured) | 6 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Headache | 20 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (measured) | 16 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Tenderness | 27 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (functional) | 5 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Pain | 20 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Nausea | 5 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Malaise | 16 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Malaise | 9 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Myalgia | 9 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Fever | 1 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (functional) | 5 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Headache | 15 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (functional) | 7 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (measured) | 10 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Tenderness | 30 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Pain | 28 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (measured) | 5 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Nausea | 2 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Malaise | 11 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Headache | 14 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (functional) | 6 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (measured) | 8 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (measured) | 3 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Fever | 3 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Myalgia | 12 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Nausea | 3 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Pain | 15 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Tenderness | 20 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (functional) | 2 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (functional) | 7 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Tenderness | 66 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Pain | 38 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Headache | 32 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Myalgia | 23 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Malaise | 25 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Fever | 5 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (functional) | 5 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (measured) | 13 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Nausea | 9 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (measured) | 6 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Fever | 9 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Tenderness | 76 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Pain | 44 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (measured) | 12 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Nausea | 11 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Headache | 40 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (measured) | 19 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Redness (functional) | 15 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Myalgia | 25 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Swelling (functional) | 11 Participants |
| VN/VN, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination | Malaise | 28 Participants |
Secondary
Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after the second vaccination and review the Memory Aid with clinic staff at a follow up visit on Day 8. Subjects are counted if they indicated experiencing the symptom at any severity during the reporting period. The symptoms of redness and swelling were solicited as both functional grading as impact on daily activies as well as collected as a measured value in mm. The number reported for all symptoms is the number reporting greater than none.
Time frame: 7 days after second vaccination
Population: All subjects receiving the second vaccination are included in this outcome measure. The VN, Day 0 Group received only one dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Myalgia | 5 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Fever | 0 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Malaise | 3 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (functional) | 4 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Headache | 7 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (measured) | 3 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Pain | 9 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Tenderness | 15 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Nausea | 4 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (measured) | 7 Participants |
| VN/VN, Day 0, 7 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (functional) | 1 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (functional) | 2 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Nausea | 2 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Fever | 2 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (functional) | 2 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Myalgia | 4 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Malaise | 4 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Pain | 8 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Headache | 8 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Tenderness | 14 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (measured) | 4 Participants |
| VN/VN, Day 0, 14 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (measured) | 3 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Nausea | 3 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Tenderness | 21 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (measured) | 6 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Malaise | 8 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (functional) | 7 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (functional) | 5 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Fever | 3 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Myalgia | 5 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (measured) | 11 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Headache | 8 Participants |
| I/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Pain | 12 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Tenderness | 24 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Pain | 7 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (functional) | 1 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Myalgia | 5 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (functional) | 3 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Nausea | 2 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (measured) | 1 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (measured) | 5 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Headache | 11 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Malaise | 4 Participants |
| VN/I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Fever | 1 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Malaise | 13 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Myalgia | 12 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (measured) | 4 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (functional) | 2 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Pain | 19 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Headache | 12 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (functional) | 3 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Fever | 5 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Tenderness | 28 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Nausea | 2 Participants |
| VN+I/VN+I, Day 0, 28 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (measured) | 7 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Malaise | 6 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Headache | 10 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Nausea | 2 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (measured) | 6 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Fever | 3 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Myalgia | 5 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Pain | 10 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Tenderness | 26 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (functional) | 7 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (measured) | 10 Participants |
| VN/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (functional) | 5 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (functional) | 7 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Fever | 3 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Malaise | 9 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (functional) | 2 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (measured) | 8 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Myalgia | 5 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Nausea | 5 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (measured) | 3 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Tenderness | 22 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Pain | 11 Participants |
| I/I, Day 0, 180 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Headache | 13 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Tenderness | 71 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (functional) | 11 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Myalgia | 22 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Fever | 6 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Redness (measured) | 22 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Malaise | 24 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Pain | 49 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (measured) | 13 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Swelling (functional) | 9 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Nausea | 11 Participants |
| VN, Day 0 | Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination | Headache | 22 Participants |