A Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline Biologicals' Influenza Vaccine GSK3206641A Administered in Adults 18 to 64 Years of Age and 65 Years of Age and Older

Center for Biologics Evaluation and Research (CBER) criteria for seroprotection rate (SPR) for 18 to 64 years of age is shown if the Lower Limit (LL) of the 99.17% confidence interval (CI) for the SPR meets or exceeds 70%, and for greater than or equal to (≥) 65 years of age if the LL of the 99.17% CI for the SPR meets or exceeds 60%. SPR is defined as the percentage of participants with an HI antibody titer ≥40 1/dilution (DIL). The percentage of participants was calculated along with Clopper-Pearson exact two-sided 99.17% CIs.

CBER criteria for seroconversion rate (SCR) for 18 to 64 years of age is shown if LL of the 99.17% CI for the SCR meets or exceeds 40%, and for ≥65 years of age, if the LL of the 99.17% CI for the SCR meets or exceeds 30%. Seroconversion is defined as a post-vaccination antibody titer ≥40 1/DIL in the serum of participants seronegative before vaccination (i.e. titer < assay cut-off at Day 1). For seropositive participants (i.e. titer ≥ assay cut-off at Day 1), seroconversion requires a 4-fold rise in post-vaccination HI antibody titer (but at least a titer of 40 1/DIL). The percentage of participants was calculated with Clopper-Pearson exact two-sided 99.17% CIs.

Note: The cut-off value for antibody titer was defined by the laboratory before the analysis.

Solicited administered site events assessed were pain, redness and swelling. Any Pain = occurrence of symptom regardless of intensity grade. Any Redness or any Swelling symptom = any symptom having a surface diameter greater than (>) 20 millimeters (mm).

Solicited administered site events assessed were pain, redness and swelling. Any Pain = occurrence of symptom regardless of intensity grade. Any Redness or any Swelling symptom = any symptom having a surface diameter >20 mm.

Solicited systemic events assessed were fatigue, fever, headache, muscle ache all over body, joint pain, shivering, sweating and gastrointestinal symptoms (Nausea, vomiting, diarrhea and abdominal pain). Any = occurrence of symptom regardless of intensity grade. Fever was defined as temperature ≥38 degrees Celsius (°C) for oral route (preferred location for measuring temperature).

Solicited systemic events assessed were fatigue, fever, headache, muscle ache all over body, joint pain, shivering, sweating and gastrointestinal symptoms (Nausea, vomiting, diarrhea and abdominal pain). Any = occurrence of symptom regardless of intensity grade. Fever was defined as temperature ≥38°C for oral route (preferred location for measuring temperature).

An unsolicited adverse event (AE) is an AE that was not solicited using a Participant Diary and that was spontaneously communicated by a participant who had signed the informed consent. Unsolicited AEs include serious and non-serious AEs. Potential unsolicited AEs may have been medically attended (i.e. symptoms or illnesses requiring a hospitalization, or emergency room visit, or visit to/by a health care provider). Unsolicited AEs that were not medically attended nor perceived as a concern by participant were collected during interview with the participants and by review of available medical records at the following visit. An unsolicited adverse event is any event reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

An unsolicited AE is an AE that was not solicited using a Participant Diary and that was spontaneously communicated by a participant who has signed the informed consent. Unsolicited AEs include serious and non-serious AEs. Potential unsolicited AEs may have been medically attended (i.e. symptoms or illnesses requiring a hospitalization, or emergency room visit, or visit to/by a health care provider). Unsolicited AEs that were not medically attended nor perceived as a concern by participant are collected during interview with the participants and by review of available medical records at the next visit. An unsolicited adverse event is any event reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

MAEs were defined as adverse events with medically-attended visits that are not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason.

MAEs were defined as adverse events with medically-attended visits that are not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason.

A SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant. Abnormal pregnancy outcomes were also considered (e.g. spontaneous abortion, fatal death, stillbirth, congenital anomalies, ectopic pregnancy) or other situations where medical or scientific judgement was exercised in deciding whether reporting was appropriate.

pIMDs are a subset of adverse events of special interest that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune etiology.

pIMDs are a subset of adverse events of special interest that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune etiology.

A SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant. Abnormal pregnancy outcomes were also considered (e.g. spontaneous abortion, fatal death, stillbirth, congenital anomalies, ectopic pregnancy) or other situations where medical or scientific judgement was exercised in deciding whether reporting was appropriate.

HI antibody titers were expressed as Geometric Mean Titers (GMTs). The GMTs calculations were performed by taking the anti-log of the mean of the titer transformations. Values for titers below the assay cutoff will be assigned half the assay cut-off value for the purpose of GMT computation.

Note: The cut-off value for HI titer was defined by the laboratory before the analysis.

A seropositive participant is a participant whose antibody titer was greater than or equal to the assay cut-off value.

Note: The cut-off value for antibody titer was defined by the laboratory before the analysis.

Seroconversion rate is defined as the percentage of participants with a post-vaccination antibody titer ≥40 1/DIL in the serum of participants seronegative before vaccination (i.e. titer < assay cut-off at Day 1). For seropositive participants (i.e. titer ≥ assay cut-off at Day 1), seroconversion required a 4-fold rise in post-vaccination HI antibody titer (but at least a titer of 40 1/DIL).

Note: The cut-off value for antibody titer was defined by the laboratory before the analysis.

SPR is defined as the percentage of participants with HI antibody titer ≥40 1/DIL.

Note: The cut-off value for antibody titer was defined by the laboratory before the analysis.

MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 1): post-vaccination GMT over pre-vaccination GMT.

Anti-MN antibody titers were expressed as GMTs. The GMTs calculations were performed by taking the antilog of the mean of the log titer transformations. Values for the neutralisation titers below the assay cut-off were assigned half the assay cut-off value for the purpose of GMT computation. MN analyses were performed on the MN subset that included approximately 420 participants (60 per group). The first 30 participants per treatment group were selected in the ≥65 age group and then the first 15 participants in 18 to 49 years and 50 to 64 years age groups. If there were not 15 participants for the 18 to 49 or 50 to 64 years age groups, they were selected whichever had the smaller number fully and then had a total of 30 for the total among these 2 age groups per treatment group. All samples were collected first, then selected for the subset.

A seropositive participant is a participant whose antibody titer was greater than or equal to the assay cut-off value.

Note: The cut-off value for antibody titer was defined by the laboratory before the analysis. MN analyses were performed on the MN subset.

VRR is expressed as the percentage of participants with a vaccine response defined as at least a 4-fold increase in antibody titer as compared to the antibody titer at Day 1 (pre-vaccination). Antibody titers below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of vaccine response calculation. For VRR, the percentage of participants was calculated with Clopper-Pearson exact two-sided 95% CIs. MN analyses were performed on the MN subset.