A Study to Evaluate Safety and Immunogenicity of One or Two Booster Vaccinations With H5N6 Influenza Vaccine in Adults Primed With H5N1 Influenza Vaccine or Unprimed

• aH5N6c on Day 1 (Biological): MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N6 vaccine (aH5N6c) for intramuscular (IM) administration, containing 7.5 μg H5N6 hemagglutinin (HA) (A/Guangdong/18SF020/2018 (H5N6)-like) + 0.25 mL MF59 (approximately 0.5 mL total volume)
• aH5N6c on Day 22 (Biological): MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N6 vaccine (aH5N6c) for intramuscular (IM) administration, containing 7.5 μg H5N6 HA (A/Guangdong/18SF020/2018 (H5N6)-like) + 0.25 mL MF59 (approximately 0.5 mL total volume) given 3 weeks after the first aH5N6c vaccination
• Placebo on Day 22 (Biological): Saline placebo (sterile, 0.5 mL) given 3 weeks after the aH5N6c vaccination

Primary outcomes

• Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HI) Antibodies Against the H5N6 Strain [Day 1, Day 8, Day 22, Day 43]: GMT pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the per-protocol set (PPS); definitions are provided in the Statistical Analysis Plan (SAP). The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.
• Geometric Mean Fold Increase (GMFI) of HI Antibodies Against the H5N6 Strain [Day 1, Day 8, Day 22, Day 43]: GMFI 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2 compared to pre-vaccination (Day 1) Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.
• Percentage of Subjects With HI Titers ≥1:40 Against the H5N6 Strain [Day 1, Day 8, Day 22, Day 43]: Pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.
• Percentage of Subjects With Seroconversion Against the H5N6 Strain [Day 8, Day 22, Day 43]: Seroconversion 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2, defined as a ≥4-fold increase in HI titer post-vaccination in those with pre-vaccination titer ≥1:10, or a post-vaccination HI titer ≥1:40 for subjects with baseline titer <1:10 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.

Secondary outcomes

• GMT of HI Antibodies Against the H5N1 Strain [Day 1, Day 8, Day 22, Day 43, Day 202]: GMT pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.
• GMFI of HI Antibodies Against the H5N1 Strain [Day 1, Day 8, Day 22, Day 43, Day 202]: GMFI 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2 compared to pre-vaccination (Day 1) Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.
• Percentage of Subjects With HI Titers ≥1:40 Against the H5N1 Strain [Day 1, Day 8, Day 22, Day 43, Day 202]: Pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.
• Percentage of Subjects With Seroconversion Against the H5N1 Strain [Day 8, Day 22, Day 43, Day 202]: Seroconversion 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2, defined as a ≥4-fold increase in HI titer post-vaccination in those with pre-vaccination titer ≥1:10, or a post-vaccination HI titer ≥1:40 for subjects with baseline titer <1:10 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.
• GMT of HI Antibodies Against the H5N6 Strain [Day 202]: GMT 6 months post-vaccination 2
• GMFI of HI Antibodies Against the H5N6 Strain [Day 1, Day 202]: GMFI 6 months post-vaccination 2 compared to pre-vaccination (Day 1)
• Percentage of Subjects With HI Titers ≥1:40 Against the H5N6 Strain [Day 202]: 6 months post-vaccination 2
• Percentage of Subjects With Seroconversion Against the H5N6 Strain [Day 202]: Seroconversion 6 months post-vaccination 2, defined as a ≥4-fold increase in HI titer post-vaccination in those with pre-vaccination titer ≥1:10, or a post-vaccination HI titer ≥1:40 for subjects with baseline titer <1:10
• Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs) [Day 1 through Day 7 and Day 22 through Day 28]: For 7 days following each vaccination
• Frequency and Severity of Unsolicited AEs [Day 1 through Day 43]: For 3 weeks following each vaccination
• Frequency of Serious AEs (SAEs), AEs Leading to Withdrawal, AEs of Special Interest (AESI) and Medically Attended AEs (MAAEs) [Day 1 through Day 202]: From vaccination until study completion

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Subjects who received 2 doses of aH5N1c vaccine or placebo in and completed the parent study V89_18 in the <65 years of age cohort.
* Individuals who can comply with study procedures including follow-up.

Exclusion Criteria:

* Females of childbearing potential who are pregnant, lactating, or who have not adhered to a specified set of contraceptive methods from at least 30 days prior to study entry and who do not plan to do so until at least 30 days after the last study vaccination.
* Progressive, unstable or uncontrolled clinical conditions.
* Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
* Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
* Abnormal function of the immune system.
* History of any medical condition considered an adverse event of special interest (AESI).
* Received immunoglobulins with immunomodulating effects or any blood products within 180 days prior to informed consent.
* Subjects, who received an influenza H5 vaccine other than in the V89_18 parent study or have a history of H5 influenza infection prior to enrollment.
* Received an investigational or non-registered medicinal product within 30 days prior to informed consent.
* Individuals who received any other vaccines \[except corona virus disease 2019 (COVID-19) vaccines\] within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this study or who are planning to receive any vaccine within 28 days from the study vaccination.
* Receipt of any COVID-19 vaccine within 7 days prior to enrollment or plan to receive any COVID-19 vaccine within 7 days from study vaccination.
* Acute (severe) febrile illness.
* A known history of Guillain-Barre Syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis.

Participant flow

Outcome results

• Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HI) Antibodies Against the H5N6 Strain (Primary), Geometric mean, titer: Group 1 5.48 (5.07 to 5.92); Group 2 5.55 (5.13 to 6.01); Group 3 5.47 (5.12 to 5.85)
• Geometric Mean Fold Increase (GMFI) of HI Antibodies Against the H5N6 Strain (Primary), Geometric mean, ratio: Group 1 3.71 (2.77 to 4.98); Group 2 4.31 (3.18 to 5.84); Group 3 1.45 (1.13 to 1.86)
• Percentage of Subjects With HI Titers ≥1:40 Against the H5N6 Strain (Primary), Number, % of participants: Group 1 0.0 (0.00 to 4.99); Group 2 0.0 (0.00 to 5.44); Group 3 1.1 (0.03 to 5.91)
• Percentage of Subjects With Seroconversion Against the H5N6 Strain (Primary), Number, % of participants: Group 1 28.4 (18.01 to 40.69); Group 2 36.1 (24.16 to 49.37); Group 3 8.9 (3.92 to 16.77)
• GMT of HI Antibodies Against the H5N1 Strain (Secondary), Geometric mean, titer: Group 1 13.16 (10.91 to 15.87); Group 2 15.54 (12.83 to 18.83); Group 3 6.89 (5.86 to 8.11)
• GMFI of HI Antibodies Against the H5N1 Strain (Secondary), Geometric mean, ratio: Group 1 11.13 (8.28 to 14.95); Group 2 11.88 (8.70 to 16.21); Group 3 1.43 (1.10 to 1.86)
• Percentage of Subjects With HI Titers ≥1:40 Against the H5N1 Strain (Secondary), Number, % of participants: Group 1 13.2 (6.23 to 23.64); Group 2 23.8 (13.98 to 36.21); Group 3 2.3 (0.28 to 7.97)
• Percentage of Subjects With Seroconversion Against the H5N1 Strain (Secondary), Number, % of participants: Group 1 77.8 (65.54 to 87.28); Group 2 72.4 (59.10 to 83.34); Group 3 8.0 (3.30 to 15.88)
• GMT of HI Antibodies Against the H5N6 Strain (Secondary), Geometric mean, titer: Group 1 21.18 (16.69 to 26.89); Group 2 19.35 (15.20 to 24.64); Group 3 10.05 (8.14 to 12.40)
• GMFI of HI Antibodies Against the H5N6 Strain (Secondary), Geometric mean, ratio: Group 1 3.82 (3.01 to 4.85); Group 2 3.49 (2.74 to 4.45); Group 3 1.81 (1.47 to 2.24)
• Percentage of Subjects With HI Titers ≥1:40 Against the H5N6 Strain (Secondary), Number, % of participants: Group 1 39.7 (28.03 to 52.30); Group 2 30.3 (19.59 to 42.85); Group 3 11.8 (5.79 to 20.57)
• Percentage of Subjects With Seroconversion Against the H5N6 Strain (Secondary), Number, % of participants: Group 1 37.3 (25.80 to 49.99); Group 2 30.2 (19.23 to 43.02); Group 3 9.6 (4.25 to 18.11)
• Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs) (Secondary), Count of participants, Participants: Group 1 54; Group 2 48; Group 3 67
• Frequency and Severity of Unsolicited AEs (Secondary), Count of participants, Participants: Group 1 23; Group 2 21; Group 3 25
• Frequency of Serious AEs (SAEs), AEs Leading to Withdrawal, AEs of Special Interest (AESI) and Medically Attended AEs (MAAEs) (Secondary), Count of participants, Participants: Group 1 3; Group 2 3; Group 3 4

Adverse events

Time frame: SAEs, AEs leading to withdrawal from the study, adverse events of special interest (AESIs), and MAAEs Day 1 through Day 202, other AEs Day 1 through Day 43

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2022-07-15)
• Statistical Analysis Plan (PDF, 2022-07-14)

• Therapeutic Area Head, Study chair, Seqirus