Prophylaxis: Influenza
Conditions
Brief summary
The purpose of this study is to evaluate the immunologic equivalence of three consecutive lots of a cell based trivalent subunit influenza vaccine (TIVc), and to assess immunogenicity, safety and tolerability of the vaccine and an egg based trivalent subunit influenza vaccine (TIVf). The study comprised 1 vaccination, 2 clinic visits, 3 reminder calls and 2 blood draws. Female subjects of childbearing potential were tested for pregnancy before the administration of the vaccine and included only if using and agreeing to continue to use contraception during the course of the study. The total study participation time per subject is about 3 weeks.
Interventions
BIOLOGICALTIVc_LOT A
Single IM (Intramuscular) administration dose of 0.5 mL of TIVc
BIOLOGICALTIVc_LOT B
Single IM administration dose of 0.5 mL of TIVc
BIOLOGICALTIVc_LOT C
Single IM administration dose of 0.5 mL of TIVc
BIOLOGICALTIVf
Single IM administration dose of 0.5 mL of TIVf
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Males or females 18 through 49 years of age. * Subjects having provided informed consent. * Individuals in good health
Exclusion criteria
* Chronic or acute illness that would interfere with the subject's safety and/or could interfere with the evaluation of study vaccine, including known history of anaphylaxis, serious vaccine reactions or hypersensitivity, known immunodeficiency or receiving immunosuppressive therapy. * Female of childbearing potential not using acceptable contraceptive methods, pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunologic Equivalence of 3 Consecutive Influenza Vaccine (TIVc) Production Lots. | Day 22 | Hemagglutination inhibition (HI) geometric mean titers (GMTs) achieved by subjects, for each three vaccine strains, three weeks after one vaccination of one lot of TIVc vaccine (Day 22), evaluated using HI antigen assay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | Day 22 | Percentages of subjects achieving HI seroconversion after each of three vaccine strains were measured three weeks after vaccination of TIVc or TIVf vaccine (day 22). Percentages of subjects who achieved HI titer ≥1:40 against each of three vaccine strains were measured three weeks after one vaccination of TIVc or TIVf vaccine. HI assay analysis for TIVc vaccine was based on cell-based antigen and for TIVf vaccine was based on egg based antigen. According to Center for Biologics Evaluation and Research recommendations (CBER 2007), CBER criteria are met when the lower limit of the 2-sided 95% CI for seroconversion/significant increase is ≥ 40%, and the lower limit of the 2-sided 95% CI for HI titers ≥ 1:40 is ≥ 70%. |
| Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Day 1 through day 7 (without 30 min) | Safety was assessed as the number of subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after vaccination of TIVc and control vaccines. |
| Number of Subjects With Unsolicited Adverse Events | Day 1 through day 22 | Safety was assessed as the number of subjects who reported Unsolicited Adverse Events after vaccination of TIVc and control vaccine. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled at Twenty five study centers in the United States of America.
Pre-assignment details
All enrolled subjects were included in the trial.
Participants by arm
| Arm | Count |
|---|---|
| TIVc_LOT A Subjects 18 to ≤ 49 years of age who received one vaccination with an investigational vaccine TIVc from Lot A | 387 |
| TIVc_LOT B Subjects 18 to ≤ 49 years of age who received one vaccination with an investigational vaccine TIVc from Lot B | 392 |
| TIVc_LOT C Subjects 18 to ≤ 49 years of age who received one vaccination with an investigational vaccine TIVc from Lot C | 392 |
| TIVf Subjects 18 to ≤ 49 years of age who received one vaccination of Control vaccine TIVf | 390 |
| Total | 1,561 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 6 | 6 | 9 | 3 |
| Overall Study | OTHER | 1 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | TIVc_LOT A | TIVc_LOT B | TIVc_LOT C | TIVf | Total |
|---|---|---|---|---|---|
| Age, Continuous | 32.4 years STANDARD_DEVIATION 9.1 | 33.1 years STANDARD_DEVIATION 8.8 | 33.8 years STANDARD_DEVIATION 8.8 | 33.2 years STANDARD_DEVIATION 9 | 33.1 years STANDARD_DEVIATION 8.9 |
| Sex: Female, Male FEMALE | 221 Participants | 227 Participants | 243 Participants | 250 Participants | 941 Participants |
| Sex: Female, Male MALE | 166 Participants | 165 Participants | 149 Participants | 140 Participants | 620 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 709 / 1,169 | 237 / 391 | 946 / 1,560 |
| serious Total, serious adverse events | 0 / 1,169 | 2 / 391 | 2 / 1,560 |
Outcome results
Primary
Immunologic Equivalence of 3 Consecutive Influenza Vaccine (TIVc) Production Lots.
Hemagglutination inhibition (HI) geometric mean titers (GMTs) achieved by subjects, for each three vaccine strains, three weeks after one vaccination of one lot of TIVc vaccine (Day 22), evaluated using HI antigen assay.
Time frame: Day 22
Population: Per Protocol Set(PPS) All subjects in the FAS (Full Analysis Set) Immunogenicity Population who were not excluded due to reasons defined prior to unblinding or analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| TIVc_LOT A | Immunologic Equivalence of 3 Consecutive Influenza Vaccine (TIVc) Production Lots. | B Massachusetts/2/2012 (B) | 178 Titers |
| TIVc_LOT A | Immunologic Equivalence of 3 Consecutive Influenza Vaccine (TIVc) Production Lots. | A/Texas/50/2012 (H3N2) | 466 Titers |
| TIVc_LOT A | Immunologic Equivalence of 3 Consecutive Influenza Vaccine (TIVc) Production Lots. | A/Brisbane/10/2010 (H1N1) | 667 Titers |
| TIVc_LOT B | Immunologic Equivalence of 3 Consecutive Influenza Vaccine (TIVc) Production Lots. | B Massachusetts/2/2012 (B) | 175 Titers |
| TIVc_LOT B | Immunologic Equivalence of 3 Consecutive Influenza Vaccine (TIVc) Production Lots. | A/Brisbane/10/2010 (H1N1) | 738 Titers |
| TIVc_LOT B | Immunologic Equivalence of 3 Consecutive Influenza Vaccine (TIVc) Production Lots. | A/Texas/50/2012 (H3N2) | 472 Titers |
| TIVc_LOT C | Immunologic Equivalence of 3 Consecutive Influenza Vaccine (TIVc) Production Lots. | A/Texas/50/2012 (H3N2) | 437 Titers |
| TIVc_LOT C | Immunologic Equivalence of 3 Consecutive Influenza Vaccine (TIVc) Production Lots. | A/Brisbane/10/2010 (H1N1) | 655 Titers |
| TIVc_LOT C | Immunologic Equivalence of 3 Consecutive Influenza Vaccine (TIVc) Production Lots. | B Massachusetts/2/2012 (B) | 172 Titers |
Comparison: To demonstrate immunologic equivalence of three consecutive TIVc production lots as evaluated by HI antibody responses after vaccination for all 3 influenza strains at day 22.95% CI: [0.667, 1.5]ANCOVA
Comparison: To demonstrate immunologic equivalence of three consecutive TIVc production lots as evaluated by HI antibody responses after vaccination for for all 3 influenza strains at day 2295% CI: [0.667, 1.5]ANCOVA
Comparison: To demonstrate immunologic equivalence of three consecutive TIVc production lots as evaluated by HI antibody responses after vaccination for all 3 influenza strains at day 2295% CI: [0.667, 1.5]ANCOVA
Secondary
Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf
Safety was assessed as the number of subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after vaccination of TIVc and control vaccines.
Time frame: Day 1 through day 7 (without 30 min)
Population: Solicited Safety Set-All subjects in the exposed set with any solicited AE data postvaccination or indicators of solicited AEs postvaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Induration | 168 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Erythema | 208 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Ecchymosis | 76 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Pain | 481 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Nausea | 91 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Myalgia | 109 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Arthralgia | 84 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Headache | 259 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Fatigue | 221 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Diarrhea | 85 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Chills | 45 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Loss of appetite | 66 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Vomiting | 18 Subjects |
| TIVc_LOT A | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Fever (≥38°C) | 7 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Chills | 11 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Induration | 62 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Headache | 80 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Erythema | 77 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Vomiting | 9 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Ecchymosis | 30 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Fatigue | 77 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Pain | 135 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Loss of appetite | 39 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Nausea | 30 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Diarrhea | 47 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Myalgia | 28 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Fever (≥38°C) | 2 Subjects |
| TIVc_LOT B | Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIVc and TIVf | Arthralgia | 28 Subjects |
Secondary
Number of Subjects With Unsolicited Adverse Events
Safety was assessed as the number of subjects who reported Unsolicited Adverse Events after vaccination of TIVc and control vaccine.
Time frame: Day 1 through day 22
Population: Unsolicited Safety Set-All subjects in the exposed set with unsolicited AE data postvaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIVc_LOT A | Number of Subjects With Unsolicited Adverse Events | Any AE | 139 Subjects |
| TIVc_LOT A | Number of Subjects With Unsolicited Adverse Events | AE leading to withdrawal | 0 Subjects |
| TIVc_LOT A | Number of Subjects With Unsolicited Adverse Events | SAE | 0 Subjects |
| TIVc_LOT A | Number of Subjects With Unsolicited Adverse Events | Medically attended AE | 28 Subjects |
| TIVc_LOT A | Number of Subjects With Unsolicited Adverse Events | Possibly or probably related AE | 50 Subjects |
| TIVc_LOT A | Number of Subjects With Unsolicited Adverse Events | New Onset of Chronic Disease | 2 Subjects |
| TIVc_LOT A | Number of Subjects With Unsolicited Adverse Events | Possibly or probably related SAE | 0 Subjects |
| TIVc_LOT A | Number of Subjects With Unsolicited Adverse Events | Death | 0 Subjects |
| TIVc_LOT B | Number of Subjects With Unsolicited Adverse Events | Death | 0 Subjects |
| TIVc_LOT B | Number of Subjects With Unsolicited Adverse Events | Any AE | 38 Subjects |
| TIVc_LOT B | Number of Subjects With Unsolicited Adverse Events | Possibly or probably related AE | 14 Subjects |
| TIVc_LOT B | Number of Subjects With Unsolicited Adverse Events | SAE | 2 Subjects |
| TIVc_LOT B | Number of Subjects With Unsolicited Adverse Events | Possibly or probably related SAE | 1 Subjects |
| TIVc_LOT B | Number of Subjects With Unsolicited Adverse Events | AE leading to withdrawal | 0 Subjects |
| TIVc_LOT B | Number of Subjects With Unsolicited Adverse Events | Medically attended AE | 9 Subjects |
| TIVc_LOT B | Number of Subjects With Unsolicited Adverse Events | New Onset of Chronic Disease | 1 Subjects |
Secondary
Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine.
Percentages of subjects achieving HI seroconversion after each of three vaccine strains were measured three weeks after vaccination of TIVc or TIVf vaccine (day 22). Percentages of subjects who achieved HI titer ≥1:40 against each of three vaccine strains were measured three weeks after one vaccination of TIVc or TIVf vaccine. HI assay analysis for TIVc vaccine was based on cell-based antigen and for TIVf vaccine was based on egg based antigen. According to Center for Biologics Evaluation and Research recommendations (CBER 2007), CBER criteria are met when the lower limit of the 2-sided 95% CI for seroconversion/significant increase is ≥ 40%, and the lower limit of the 2-sided 95% CI for HI titers ≥ 1:40 is ≥ 70%.
Time frame: Day 22
Population: FAS(Full Analysis Set) All subjects in the Enrolled Population who: ▫ receive a study vaccination and provide immunogenicity data at Day 1 and at Day 22 FAS populations was analyzed as randomized (i.e., according to the vaccine a subject was designated to receive, which may be different from the vaccine the subject actually received).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIVc_LOT A | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | Influenza A H1N1 Brisbane/2010 CC Ab-SC(1143,379 ) | 60 percentages of subjects |
| TIVc_LOT A | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | A/Texas/50/2012 (H3N2)- Seroconversion | 49 percentages of subjects |
| TIVc_LOT A | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | B Massachusetts/2/2012 (B) - Seroconversion | 39 percentages of subjects |
| TIVc_LOT A | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | Influenza A H1N1 Brisbane/2010 CC Ab-HI ≥1:40Day22 | 99 percentages of subjects |
| TIVc_LOT A | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | A/Texas/50/2012 (H3N2)- HI ≥1:40(Day 22) | 100 percentages of subjects |
| TIVc_LOT A | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | B Massachusetts/2/2012 (B) - HI ≥1:40 (Day 22) | 98 percentages of subjects |
| TIVc_LOT B | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | A/Texas/50/2012 (H3N2)- HI ≥1:40(Day 22) | 100 percentages of subjects |
| TIVc_LOT B | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | Influenza A H1N1 Brisbane/2010 CC Ab-SC(1143,379 ) | 69 percentages of subjects |
| TIVc_LOT B | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | Influenza A H1N1 Brisbane/2010 CC Ab-HI ≥1:40Day22 | 99 percentages of subjects |
| TIVc_LOT B | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | A/Texas/50/2012 (H3N2)- Seroconversion | 63 percentages of subjects |
| TIVc_LOT B | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | B Massachusetts/2/2012 (B) - HI ≥1:40 (Day 22) | 92 percentages of subjects |
| TIVc_LOT B | Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIVc and TIVf Vaccine. | B Massachusetts/2/2012 (B) - Seroconversion | 45 percentages of subjects |