Safety and Immunogenicity of Different Formulations of Monovalent Influenza A/Astrakhan/3212/2020 Like (H5N8) Virus Vaccine With AS03 Adjuvant System in Medically Stable Adults

Phase 1

Completed

Conditions: Influenza, Human

Interventions: Biological: FLU Q-PAN H5N8 375_B
Biological: FLU Q-PAN H5N8 375_A
Biological: FLU Q-PAN H5N8 750_B
Biological: FLU Q-PAN H5N8 750_A

Registration Number: NCT05975840

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of this study is to assess the safety and immunogenicity of different formulations of monovalent Influenza A/Astrakhan/3212/2020-like virus vaccine with AS03 adjuvant system in adults greater than or equal to (\>=)18 years of age.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 518

Inclusion Criteria

Medically stable participants as established by medical history and clinical examination before entering into the study.
A male or female >=18 years of age at the time of signing consent form.
Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study specific procedure.
Female participants of childbearing potential or non-childbearing potential may be enrolled in the study if specific criteria are met.

Exclusion Criteria

Current diagnosis or history of autoimmune disorder(s) except hypothyroidism due to Hashimoto's thyroiditis.
History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
Clinically significant acute or chronic pulmonary, cardiovascular, hepatic, or renal disease that appears uncontrolled or untreated, as determined by history or physical examination.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history, physical examination, or abnormalities in screening blood tests.
Recurrent history of or uncontrolled neurological disorders or seizures.
History of Guillain-Barré syndrome.
Diagnosed with cancer, or treatment for cancer within 3 years.
- Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible.
- Persons with a history of histologically confirmed basal cell carcinoma of the skin successfully treated with local excision only, are accepted and are eligible, but other histologic types of skin cancer are exclusionary.
- Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylaxis are eligible.
Documented human immunodeficiency virus-positive participants.
Bedridden participants.
Personal or family history of narcolepsy.
Food and Drug Administration (FDA) toxicity Grade 2, or greater, laboratory tests at Screening.
Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
Use of any investigational or non-registered product other than the study vaccine during the period beginning 30 days before the first dose of study vaccine (Day -29 to Day 1), or planned use during the entire study period.
Use of public health emergency vaccines like coronavirus disease 2019 (COVID-19), Monkey pox (mpox) etc. These can be given at any time, but there should a gap of 2 - weeks before a dose of study vaccine can be given.
Use of any licensed vaccines: prior to receipt of the study vaccine and continuing up to 3 weeks after receiving the dose 2 of study vaccine.
Administration of long-acting immune-modifying drugs at any time during the study period.
Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first dose of study vaccine or planned administration during the study period.
Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine dose and through the entire study period. For corticosteroids, this will mean prednisone equivalent >=20 milligrams/day for 14 days or a total of >=280 mg of prednisone equivalent dose in any 14-day period. Inhaled and topical steroids are allowed.
Pregnant or lactating female.
Female planning to become pregnant or planning to discontinue contraceptive precautions within 2 months after completion of the vaccination series.
History of/or current drug/alcohol abuse.
Any study personnel or their immediate dependents, family, or household member.
Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non investigational vaccine/product.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Age group 18-64: FLU Q-PAN H5N8 375_B	FLU Q-PAN H5N8 375_B	Participants received 2 doses of 375_B vaccine formulation, 21 days apart.
Age group 18-64: FLU Q-PAN H5N8 375_A	FLU Q-PAN H5N8 375_A	Participants received 2 doses of 375_A vaccine formulation, 21 days apart.
Age group 18-64: FLU Q-PAN H5N8 750_B	FLU Q-PAN H5N8 750_B	Participants received 2 doses of 750_B vaccine formulation, 21 days apart.
Age group 18-64: FLU Q-PAN H5N8 750_A	FLU Q-PAN H5N8 750_A	Participants received 2 doses of 750_A vaccine formulation, 21 days apart.
Age group >=65: FLU Q-PAN H5N8 375_B	FLU Q-PAN H5N8 375_B	Participants received 2 doses of 375_B vaccine formulation, 21 days apart.
Age group >=65: FLU Q-PAN H5N8 375_A	FLU Q-PAN H5N8 375_A	Participants received 2 doses of 375_A vaccine formulation, 21 days apart.
Age group >=65: FLU Q-PAN H5N8 750_B	FLU Q-PAN H5N8 750_B	Participants received 2 doses of 750_B vaccine formulation, 21 days apart.
Age group >=65: FLU Q-PAN H5N8 750_A	FLU Q-PAN H5N8 750_A	Participants received 2 doses of 750_A vaccine formulation, 21 days apart.

Primary Outcome Measures

Name	Time	Method
Hemagglutination-inhibiting (HI) Antibody Titers Against Vaccine-homologous H5N8	At Day 43	Antibody titers were presented as geometric mean titers (GMTs).
Geometric Mean Fold Rise (GMFR) of Serum HI Antibody Titers Against Vaccine-homologous H5N8	At Day 43	The GMFR is defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus.
Number of Seroprotected (SP) Participants for HI Antibody Titers	At Day 43	Seroprotection rate is defined as the number of participants with HI titer value greater than or equal to (\>=) 1:40 which is considered as indicating protection.
Number of Participants Reporting Each Solicited Administration Site Event Following Dose 1	7 days (Day 1 to Day 7) following dose 1	Solicited administration site events included pain, redness and swelling.
Number of Participants Reporting Each Solicited Administration Site Event Following Dose 2	7 days (Day 22 to Day 28) following dose 2	Solicited administration site events included pain, redness and swelling.
Number of Participants Reporting Each Solicited Systemic Event Following Dose 1	7 days (Day 1 to Day 7) following dose 1	Solicited systemic events included fatigue, fever, headache, muscle ache, joint pain, shivering (chills), sweating, gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain). Fever is defined as temperature \>=38 degrees Celsius (°C) for oral route (preferred location for measuring temperature).
Number of Participants Reporting Each Solicited Systemic Event Following Dose 2	7 days (Day 22 to Day 28) following dose 2	Solicited systemic events included fatigue, fever, headache, muscle ache, joint pain, shivering (chills), sweating, gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain). Fever is defined as temperature \>=38 degrees Celsius (°C) for oral route (preferred location for measuring temperature).
Number of Participants With Any Increase in Toxicity Grading in Hematological Laboratory Parameters Following Dose 1	7 days (Day 1 to Day 7) following dose 1	Hemoglobin, white blood cells (WBC) increase, WBC decrease, platelets, neutrophils, lymphocytes and eosinophils were graded by FDA toxicity grading scale in which grades are Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life threatening. Blood samples were collected for safety laboratory tests from the first 50% of participants of each age and dose group, at 7 days following each vaccination (i.e., Visit 2 and Visit 4).
Number of Participants With Any Increase in Toxicity Grading in Hematological Laboratory Parameters Following Dose 2	7 days (Day 22 to Day 28) following dose 2	Hemoglobin, WBC increase, WBC decrease, platelets, neutrophils, lymphocytes and eosinophils were graded by FDA toxicity grading scale in which grades are Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life threatening. Blood samples were collected for safety laboratory tests from the first 50% of participants of each age and dose group, at 7 days following each vaccination (i.e., Visit 2 and Visit 4).
Number of Participants With Any Increase in Toxicity Grading in Biochemical Laboratory Parameters Following Dose 1	7 days (Day 1 to Day 7) following dose 1	Sodium increase, sodium decrease, potassium increase, potassium decrease, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin and blood urea nitrogen (BUN) were graded by FDA toxicity grading scale in which grades are Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life threatening. Blood samples were collected for safety laboratory tests from the first 50% of participants of each age and dose group, at 7 days following each vaccination (i.e., Visit 2 and Visit 4).
Number of Participants With Any Increase in Toxicity Grading in Biochemical Laboratory Parameters Following Dose 2	7 days (Day 22 to Day 28) following dose 2	Sodium increase, sodium decrease, potassium increase, potassium decrease, creatinine, ALT, AST, alkaline phosphatase, total bilirubin and BUN were graded by FDA toxicity grading scale in which grades are Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life threatening. Blood samples were collected for safety laboratory tests from the first 50% of participants of each age and dose group, at 7 days following each vaccination (i.e., Visit 2 and Visit 4).
Number of Participants Reporting Unsolicited AEs Following Dose 1	21 days (Day 1 to Day 22) following dose 1	An unsolicited adverse event is defined as an adverse event that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events.
Number of Participants Reporting Unsolicited AEs Following Dose 2	21 days (Day 22 to Day 43) following dose 2	An unsolicited adverse event is defined as an adverse event that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events.
Number of Participants Reporting Unsolicited Medically Attended Adverse Events (MAEs) Following Dose 1	21 days (Day 1 to Day 22) following dose 1	MAE is defined as an AE that results in an unscheduled visit to a medical professional (e.g., symptoms or illnesses requiring a hospitalization, emergency room visit, or visit to/by a healthcare provider).
Number of Participants Reporting Unsolicited MAEs Following Dose 2	21 days (Day 22 to Day 43) following dose 2
Number of Participants Reporting Unsolicited MAEs up to 6 Months Post Dose 2 (Administered on Day 22)	Up to 6 months post dose 2 (administered on Day 22)
Number of Participants Reporting Serious Adverse Events (SAEs) up to Day 43	From Day 1 to Day 43	An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an abnormal pregnancy outcome (e.g., spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy), or is a suspected transmission of any infectious agent via an authorized medicinal product.
Number of Participants Reporting SAEs up to 6 Months Post Dose 2 (Administered on Day 22)	Day 1 to 6 months post dose 2 (administered on Day 22)
Number of Participants Reporting Potential Immune-mediated Diseases (pIMDs) up to Day 43	From Day 1 to Day 43	pIMDs are defined a subset of AEs of special interest that includes autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
Number of Participants Reporting pIMDs up to 6 Months Post Dose 2 (Administered on Day 22)	Day 1 to 6 months post dose 2 (administered on Day 22)

Secondary Outcome Measures

Name	Time	Method
HI Antibody Titers Against Vaccine-homologous H5N8	Day 1, Day 22, and 6 months post dose 2 (administered on Day 22)	Antibody titers were presented as geometric mean titers (GMTs).
GMFR of Serum HI Antibody Titers Against Vaccine-homologous H5N8	At Day 22, and 6 months post dose 2 (administered on Day 22)	The GMFR is defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus.
Number of Seroprotected Participants for HI Antibody Titers	At Day 1, Day 22, and 6 months post dose 2 (administered on Day 22)	Seroprotection rate is defined as the number of participants with HI titer value \>= 1:40 which is considered as indicating protection.
Number of Seroconverted Participants for HI Antibody Titers	At Day 22, Day 43 and 6 months post dose 2 (administered on Day 22)	HI seroconversion is defined as a post-vaccination titer \>=1:40 in the serum of participants with pre-vaccination titer below 1:10 or as a \>=4-fold rise in post-vaccination HI titer with pre-vaccination titer \>=1:10.
Microneutralization (MN) Antibody Titers for a Subset of Participants	At Day 1, Day 22, and 6 months post dose 2 (administered on Day 22)	Microneutralization testing was performed on 50% of the participants, randomly selected and equally distributed across the different age groups.
Number of Seropositive Participants for MN Antibody Titers for a Subset of Participants	At Day 1, Day 22, and 6 months post dose 2 (administered on Day 22)	A seropositive participant is a participant whose antibody titer is greater than or equal to the assay cut-off value of 1:40.
Number of Participants Meeting Vaccine Response (VR) Criteria of MN Antibody Titers for a Subset of Participants	At Day 22, Day 43, and 6 months post dose 2 (administered on Day 22)	MN VR is defined as titer \>=4x LLOQ for participants with pre-vaccination titer below LLOQ or a \>=4 -fold increase from pre-vaccination titer for participants with pre-vaccination titer \>=LLOQ.