Hematopoietic Cell Transplantation
Conditions
Brief summary
This randomized phase II studies the side effects of high-dose trivalent influenza vaccine or standard-dose quadrivalent inactivated influenza and how well they work in treating adult patients undergoing stem cell transplant. Season influenza can cause more severe infections in patients who have had a stem cell transplant since their immune system doesn't work as well. Influenza vaccine may provide better protection against flu in adults.
Detailed description
PRIMARY OBJECTIVES: I. To determine whether high dose (HD)-trivalent influenza vaccine (TIV) compared with standard dose (SD)-quadrivalent inactivated influenza vaccine (QIV) will increase the probability of achieving a \>= 4-fold rise in hemagglutination inhibition assay (HAI) titer, \>= 1:40 HAI titer, or a higher geometric mean titer (GMT) titer to influenza A antigens in adult hematopoietic cell transplantation (HSCT) recipients. SECONDARY OBJECTIVES: I. To determine whether HD-TIV compared with SD-QIV will increase the probability of achieving a \>= 4-fold rise in HAI titers, \>= 1:40 HAI titer, or higher GMT titers to influenza B antigens in adult HSCT recipients. II. To determine the frequency and severity of solicited local injection site adverse events (e.g. pain/tenderness, redness, and swelling at injection site) with HD-TIV compared to SD-QIV in adult HSCT recipients. III. To determine the frequency and severity of solicited systemic adverse events (e.g. fevers, headache, fatigue/malaise, nausea, body ache/myalgia, general activity level, and vomiting) with HD-TIV compared to SD-QIV in adult HSCT recipients. IV. To define the relationship between HAI titers, in vivo T and B cell phenotype, and in vitro influenza-specific T and B cell response in adult HSCT recipients receiving either HD-TIV or SD-QIV. V. To correlate HAI responses to microneutralization responses. VI. To compare the persistent HAI and microneutralization assay (MN) titers for all four antigen seven months after the last vaccine dose to assess for persistence of antibody titers. VII. To compare influenza detection by polymerase chain reaction (PCR) during influenza season in adult HSCT recipients receiving either HD-TIV or standard dose QIV. OUTLINE: Patients are randomized into 1 of 2 groups. GROUP I: Patients receive HD-TIV intramuscularly once at baseline and once between 28-42 days. GROUP II: Patients receive SD-QIV intramuscularly once at baseline and once between 28-42 days. After completion of study treatment, patients are contacted at 1-3 and 8-10 days after each vaccination visit.
Interventions
Standard Dose Quadrivalent Influenza Vaccine given intramuscularly
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALTrivalent Influenza Vaccine
High Dose Trivalent Influenza Vaccine given intramuscularly
Sponsors
Vanderbilt-Ingram Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Allogeneic HSCT recipients who are 3-23 months post-transplant; 2. ≥ 18 years of age; 3. Available for duration of study; 4. Patients with stable GVHD for at least 4 weeks will be eligible (stable is defined as no major change in systemic immunosuppressive therapy for worsening GVHD; adjustment of actual dose to obtain a stable target level is acceptable). 5. Can be reached by telephone and/or electronic communication 6. Subjects must have a platelet count of ≥30,000 to receive the immunizations. Patients requiring platelet transfusions are eligible to enroll and must have a platelet count ≥30,000 within 72 hours prior to their immunization, or platelet count ≥75,000 without transfusion documented within 30 days for subjects \<12 months post- transplant and within 90 days for subjects 12-23 months post-transplant.
Exclusion criteria
1. History of hypersensitivity to previous influenza vaccination or severe hypersensitivity to eggs/egg protein; 2. History of Guillain-Barre syndrome; 3. Evidence of hematologic malignancy or disease relapse post-transplant (stable mixed chimerism is permitted); 4. History of receiving current seasonal influenza vaccine post-transplant; 5. Pregnant female; 6. History of proven influenza disease after September 1, 2018 prior to enrollment; 7. Non-allogeneic (e.g. autologous) or syngeneic hematopoietic SCT recipients; 8. History of known active infection with HIV 9. History of cirrhosis 10. History of known latex hypersensitivity; 11. Subjects who have received stem cell boost or delayed donor lymphocyte infusion within 90 days of enrollment, including day of enrollment 12. Receipt of. IVIG/SCIG \<28 days prior to vaccination Criteria for temporarily delaying vaccine administration: The following conditions are temporary or self-limiting, and a subject may be included in the study once the condition has resolved, provided that the subject is otherwise eligible: 1. Fever ≥100.4ºF/38.0ºC (oral measurement), or an acute illness within 48 hours of enrollment 2. Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks prior to potential study vaccination. Note: if patients were eligible for vaccine 1, they will be eligible to receive vaccine 2 regardless of any changes on their GVHD status, unless it is deemed not medically safe to receive influenza vaccine. For subjects who were enrolled and vaccinated in 2017-18, and 2018-19, the goal is to enroll these same subjects who participated the previous influenza season year and then administer the same vaccination as the previous year. These subjects are referred to as repeaters. For example, subjects enrolled in 2017-18 year were eligible to enroll again in 2018-19 as repeaters. For subjects enrolled in 2018-19 year and received at least one vaccine, will be eligible to be enrolled as repeaters for 2019-2020 season.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | Visit 1 titers (baseline) were measured on day 0; visit 2 titers were measured 28-42 days after visit 1; visit 3 titers were measured 28-42 days after visit 2; and visit 4 titers were measured 138-222 days after visit 2. | Point estimates and 95% confidence intervals for proportion of subjects achieving seroprotection (≥1:40 HAI titer) and seroconversion (4-fold or greater rise in HAI titers from visit 1) for Influenza A antigens. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | Visit 1 titers (baseline) were measured on day 0; visit 2 titers were measured 28-42 days after visit 1; visit 3 titers were measured 28-42 days after visit 2; and visit 4 titers were measured 138-222 days after visit 2. | Point estimates and 95% confidence intervals for proportion of subjects achieving seroprotection (≥1:40 HAI titer) and seroconversion (4-fold or greater rise in HAI titers from visit 1) for Influenza B antigens. |
| Solicited Local Injection Site Adverse Events | Adverse events were recorded for 7 days following each vaccination or until resolution, up to study conclusion. | The proportion of subjects in each group experiencing at least one solicited AE with 95% posterior credible intervals, separated by vaccine number and adverse event type. AEs were assessed by clinicians using Tables 4 and 5 within section C16 of the protocol. Solicited injection site AEs included: pain, tenderness, erythema/redness, and swelling/induration. The diameter of any erythema/redness and swelling/induration was measured to evaluate redness size and swelling size. |
| Solicited Systemic Adverse Events | Adverse events were recorded for 7 days following each vaccination or until resolution, up to study conclusion. | The proportion of subjects in each group experiencing at least one solicited AE with 95% posterior credible intervals, separated by vaccine number and adverse event type. AEs were assessed by clinicians using Tables 4 and 5 within section C16 of the protocol. Solicited systemic AEs included: fevers, fatigue/malaise, headache, nausea, body ache/myalgia, generally activity, and vomiting. |
| Percentage of Individuals in Each Group That Test Positive for Influenza by PCR | Nasal swabs were collected at each study visit or within 48 hours if a subject presented with influenza-like symptoms throughout the duration of the study. | The percentage of breakthrough flu in vaccinated participants, separated by treatment group. |
Other
| Measure | Time frame | Description |
|---|---|---|
| B Cell Response Assessed by Mass Cytometry and In-vitro Functionality Assays | Visit 1 cell counts (baseline) were measured on day 0; visit 2 cell counts were measured 28-42 days after visit 1; visit 3 cell counts were measured 28-42 days after visit 2; and visit 4 cell counts were measured 138-222 days after visit 2. | The total number of B cells will be measured prior to each vaccination and compared to each group. |
| T Cell Response Assessed by Mass Cytometry and In-vitro Functionality Assays | Visit 1 cell counts (baseline) were measured on day 0; visit 2 cell counts were measured 28-42 days after visit 1; visit 3 cell counts were measured 28-42 days after visit 2; and visit 4 cell counts were measured 138-222 days after visit 2. | The total number of T cells will be measured prior to each vaccination and compared to each group. |
Countries
United States
Participant flow
Recruitment details
A total of 138 adults were targeted with the expectation of a 20% drop out rate, as described in Section C17 in the protocol. We were able to enroll 124 subjects with a 15% dropout rate between Visit 1 and Visit 4.
Participants by arm
| Arm | Count |
|---|---|
| Group I (HD-TIV) Patients received HD-TIV intramuscularly once at baseline (day 0) and again between 28-42 days later.
Trivalent Influenza Vaccine: High Dose Trivalent Influenza Vaccine given intramuscularly
Laboratory Biomarker Analysis: Correlative studies | 60 |
| Group 2 (SD-QIV) Patients received SD-QIV intramuscularly once at baseline (day 0) and again between 28-42 days later.
Quadrivalent Inactivated Influenza Vaccine: Standard Dose Quadrivalent Influenza Vaccine given intramuscularly
Laboratory Biomarker Analysis: Correlative studies | 64 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 5 |
| Overall Study | Investigator Request | 0 | 2 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 4 |
Baseline characteristics
| Characteristic | Group I (HD-TIV) | Group 2 (SD-QIV) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 21 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants | 43 Participants | 96 Participants |
| Age, Continuous | 52.657 years | 59.986 years | 57.815 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants | 62 Participants | 120 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 51 Participants | 60 Participants | 111 Participants |
| Region of Enrollment United States | 60 participants | 64 participants | 124 participants |
| Sex: Female, Male Female | 26 Participants | 22 Participants | 48 Participants |
| Sex: Female, Male Male | 34 Participants | 42 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 60 | 5 / 64 |
| other Total, other adverse events | 45 / 60 | 45 / 64 |
| serious Total, serious adverse events | 4 / 60 | 0 / 64 |
Outcome results
Primary
HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity
Point estimates and 95% confidence intervals for proportion of subjects achieving seroprotection (≥1:40 HAI titer) and seroconversion (4-fold or greater rise in HAI titers from visit 1) for Influenza A antigens.
Time frame: Visit 1 titers (baseline) were measured on day 0; visit 2 titers were measured 28-42 days after visit 1; visit 3 titers were measured 28-42 days after visit 2; and visit 4 titers were measured 138-222 days after visit 2.
Population: The number analyzed for each row represents the number of participants that completed the indicated visit and had a recorded HAI titer for the indicated antigen and visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 2 GMT ≥1:40 | 0.62 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 2 GMFR ≥ 4-Fold Rise | 0.23 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 3 GMT ≥1:40 | 0.75 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 3 GMFR ≥ 4-Fold Rise | 0.41 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 4 GMT ≥1:40 | 0.66 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 4 GMFR ≥ 4-Fold Rise | 0.34 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 2 GMT ≥1:40 | 0.65 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 2 GMFR ≥ 4-Fold Rise | 0.32 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 3 GMT ≥1:40 | 0.78 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 3 GMFR ≥ 4-Fold Rise | 0.49 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 4 GMT ≥1:40 | 0.66 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 4 GMFR ≥ 4-Fold Rise | 0.40 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 4 GMT ≥1:40 | 0.49 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 2 GMT ≥1:40 | 0.59 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 2 GMT ≥1:40 | 0.60 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 2 GMFR ≥ 4-Fold Rise | 0.25 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 3 GMFR ≥ 4-Fold Rise | 0.38 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 3 GMT ≥1:40 | 0.73 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 2 GMFR ≥ 4-Fold Rise | 0.19 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 3 GMFR ≥ 4-Fold Rise | 0.39 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 4 GMFR ≥ 4-Fold Rise | 0.27 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 4 GMT ≥1:40 | 0.65 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H3N2 Visit 3 GMT ≥1:40 | 0.73 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity | A/H1N1 Visit 4 GMFR ≥ 4-Fold Rise | 0.35 proportion of participants |
Secondary
HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity
Point estimates and 95% confidence intervals for proportion of subjects achieving seroprotection (≥1:40 HAI titer) and seroconversion (4-fold or greater rise in HAI titers from visit 1) for Influenza B antigens.
Time frame: Visit 1 titers (baseline) were measured on day 0; visit 2 titers were measured 28-42 days after visit 1; visit 3 titers were measured 28-42 days after visit 2; and visit 4 titers were measured 138-222 days after visit 2.
Population: The number analyzed for each row represents the number of participants that completed the indicated visit and had a recorded HAI titer for the indicated antigen and visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 2 GMT ≥1:40 | 0.73 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 2 GMFR ≥ 4-Fold Rise | 0.25 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 3 GMT ≥1:40 | 0.92 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 3 GMFR ≥ 4-Fold Rise | 0.44 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 4 GMT ≥1:40 | 0.83 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 4 GMFR ≥ 4-Fold Rise | 0.34 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 2 GMT ≥1:40 | 0.72 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 2 GMFR ≥ 4-Fold Rise | 0.07 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 3 GMT ≥1:40 | 0.80 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 3 GMFR ≥ 4-Fold Rise | 0.10 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 4 GMT ≥1:40 | 0.64 proportion of participants |
| Group I (HD-TIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 4 GMFR ≥ 4-Fold Rise | 0.09 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 4 GMT ≥1:40 | 0.84 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 2 GMT ≥1:40 | 0.79 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 2 GMT ≥1:40 | 0.87 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 2 GMFR ≥ 4-Fold Rise | 0.17 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 3 GMFR ≥ 4-Fold Rise | 0.27 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 3 GMT ≥1:40 | 0.86 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 2 GMFR ≥ 4-Fold Rise | 0.22 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 3 GMFR ≥ 4-Fold Rise | 0.29 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 4 GMFR ≥ 4-Fold Rise | 0.22 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 4 GMT ≥1:40 | 0.73 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Yamagata Visit 3 GMT ≥1:40 | 0.88 proportion of participants |
| Group 2 (SD-QIV) | HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity | B/Victoria Visit 4 GMFR ≥ 4-Fold Rise | 0.18 proportion of participants |
Secondary
Percentage of Individuals in Each Group That Test Positive for Influenza by PCR
The percentage of breakthrough flu in vaccinated participants, separated by treatment group.
Time frame: Nasal swabs were collected at each study visit or within 48 hours if a subject presented with influenza-like symptoms throughout the duration of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group I (HD-TIV) | Percentage of Individuals in Each Group That Test Positive for Influenza by PCR | 5 Participants |
| Group 2 (SD-QIV) | Percentage of Individuals in Each Group That Test Positive for Influenza by PCR | 2 Participants |
Secondary
Solicited Local Injection Site Adverse Events
The proportion of subjects in each group experiencing at least one solicited AE with 95% posterior credible intervals, separated by vaccine number and adverse event type. AEs were assessed by clinicians using Tables 4 and 5 within section C16 of the protocol. Solicited injection site AEs included: pain, tenderness, erythema/redness, and swelling/induration. The diameter of any erythema/redness and swelling/induration was measured to evaluate redness size and swelling size.
Time frame: Adverse events were recorded for 7 days following each vaccination or until resolution, up to study conclusion.
Population: The number of subjects analyzed for Vaccine 1 represents the number of subjects who attended Visit 1 and received the first vaccine. The number of subjects analyzed for Vaccine 2 represents the number of subjects who attended Visit 2 and received the second vaccine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group I (HD-TIV) | Solicited Local Injection Site Adverse Events | Vaccine 1 - Pain | 0.250 proportion of participants |
| Group I (HD-TIV) | Solicited Local Injection Site Adverse Events | Vaccine 1 - Tenderness | 0.383 proportion of participants |
| Group I (HD-TIV) | Solicited Local Injection Site Adverse Events | Vaccine 1 - Redness size | 0.067 proportion of participants |
| Group I (HD-TIV) | Solicited Local Injection Site Adverse Events | Vaccine 1 - Swelling | 0.117 proportion of participants |
| Group I (HD-TIV) | Solicited Local Injection Site Adverse Events | Vaccine 1 - Swelling size | 0.100 proportion of participants |
| Group I (HD-TIV) | Solicited Local Injection Site Adverse Events | Vaccine 2 - Pain | 0.254 proportion of participants |
| Group I (HD-TIV) | Solicited Local Injection Site Adverse Events | Vaccine 2 - Tenderness | 0.458 proportion of participants |
| Group I (HD-TIV) | Solicited Local Injection Site Adverse Events | Vaccine 2 - Redness size | 0.102 proportion of participants |
| Group I (HD-TIV) | Solicited Local Injection Site Adverse Events | Vaccine 2 - Swelling | 0.136 proportion of participants |
| Group I (HD-TIV) | Solicited Local Injection Site Adverse Events | Vaccine 2 - Swelling size | 0.119 proportion of participants |
| Group 2 (SD-QIV) | Solicited Local Injection Site Adverse Events | Vaccine 2 - Redness size | 0.000 proportion of participants |
| Group 2 (SD-QIV) | Solicited Local Injection Site Adverse Events | Vaccine 1 - Pain | 0.156 proportion of participants |
| Group 2 (SD-QIV) | Solicited Local Injection Site Adverse Events | Vaccine 2 - Pain | 0.169 proportion of participants |
| Group 2 (SD-QIV) | Solicited Local Injection Site Adverse Events | Vaccine 1 - Tenderness | 0.297 proportion of participants |
| Group 2 (SD-QIV) | Solicited Local Injection Site Adverse Events | Vaccine 2 - Swelling size | 0.034 proportion of participants |
| Group 2 (SD-QIV) | Solicited Local Injection Site Adverse Events | Vaccine 1 - Redness size | 0.047 proportion of participants |
| Group 2 (SD-QIV) | Solicited Local Injection Site Adverse Events | Vaccine 2 - Tenderness | 0.288 proportion of participants |
| Group 2 (SD-QIV) | Solicited Local Injection Site Adverse Events | Vaccine 1 - Swelling | 0.094 proportion of participants |
| Group 2 (SD-QIV) | Solicited Local Injection Site Adverse Events | Vaccine 2 - Swelling | 0.102 proportion of participants |
| Group 2 (SD-QIV) | Solicited Local Injection Site Adverse Events | Vaccine 1 - Swelling size | 0.063 proportion of participants |
Secondary
Solicited Systemic Adverse Events
The proportion of subjects in each group experiencing at least one solicited AE with 95% posterior credible intervals, separated by vaccine number and adverse event type. AEs were assessed by clinicians using Tables 4 and 5 within section C16 of the protocol. Solicited systemic AEs included: fevers, fatigue/malaise, headache, nausea, body ache/myalgia, generally activity, and vomiting.
Time frame: Adverse events were recorded for 7 days following each vaccination or until resolution, up to study conclusion.
Population: The number of subjects analyzed for Vaccine 1 represents the number of subjects who attended Visit 1 and received the first vaccine. The number of subjects analyzed for Vaccine 2 represents the number of subjects who attended Visit 2 and received the second vaccine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 1 - Nausea | 0.083 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 2 - Fever | 0.034 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 1 - Fever | 0.033 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 2 - Fatigue | 0.254 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 1 - Myalgia | 0.200 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 2 - Headache | 0.203 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 1 - Headache | 0.267 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 2 - Nausea | 0.119 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 1 - General Activity | 0.300 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 2 - Myalgia | 0.153 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 1 - Fatigue | 0.350 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 2 - General Activity | 0.305 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 2 - Vomiting | 0.000 proportion of participants |
| Group I (HD-TIV) | Solicited Systemic Adverse Events | Vaccine 1 - Vomiting | 0.017 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 2 - Vomiting | 0.017 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 1 - Fever | 0.031 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 1 - Fatigue | 0.313 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 1 - Headache | 0.188 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 1 - Nausea | 0.172 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 1 - Myalgia | 0.172 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 1 - General Activity | 0.297 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 1 - Vomiting | 0.063 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 2 - Fever | 0.068 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 2 - Fatigue | 0.254 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 2 - Headache | 0.203 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 2 - Nausea | 0.186 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 2 - Myalgia | 0.153 proportion of participants |
| Group 2 (SD-QIV) | Solicited Systemic Adverse Events | Vaccine 2 - General Activity | 0.220 proportion of participants |
Other Pre-specified
B Cell Response Assessed by Mass Cytometry and In-vitro Functionality Assays
The total number of B cells will be measured prior to each vaccination and compared to each group.
Time frame: Visit 1 cell counts (baseline) were measured on day 0; visit 2 cell counts were measured 28-42 days after visit 1; visit 3 cell counts were measured 28-42 days after visit 2; and visit 4 cell counts were measured 138-222 days after visit 2.
Other Pre-specified
T Cell Response Assessed by Mass Cytometry and In-vitro Functionality Assays
The total number of T cells will be measured prior to each vaccination and compared to each group.
Time frame: Visit 1 cell counts (baseline) were measured on day 0; visit 2 cell counts were measured 28-42 days after visit 1; visit 3 cell counts were measured 28-42 days after visit 2; and visit 4 cell counts were measured 138-222 days after visit 2.