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

GlaxoSmithKline518 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

518

Conditions

Influenza, Human

Interventions

FLU Q-PAN H5N8 375_BBIOLOGICAL

Participants received 2 doses of 375\_B vaccine formulation by intramuscular injection in the non-dominant arm.

FLU Q-PAN H5N8 375_ABIOLOGICAL

Participants received 2 doses of 375\_A vaccine formulation by intramuscular injection in the non-dominant arm.

FLU Q-PAN H5N8 750_BBIOLOGICAL

Participants received 2 doses of 750\_B vaccine formulation by intramuscular injection in the non-dominant arm.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (20)

GSK Investigational Site

Anniston, Alabama, United States

GSK Investigational Site

Mobile, Alabama, United States

Outcomes

Primary Outcomes

Hemagglutination-inhibiting (HI) Antibody Titers Against Vaccine-homologous H5N8

Antibody titers were presented as geometric mean titers (GMTs).

Time frame: At Day 43

Geometric Mean Fold Rise (GMFR) of Serum HI Antibody Titers Against Vaccine-homologous H5N8

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.

Time frame: At Day 43

Number of Seroprotected (SP) Participants for HI Antibody Titers

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.

Time frame: At Day 43

Number of Participants Reporting Each Solicited Administration Site Event Following Dose 1

Solicited administration site events included pain, redness and swelling.

Time frame: 7 days (Day 1 to Day 7) following dose 1

Number of Participants Reporting Each Solicited Administration Site Event Following Dose 2

Solicited administration site events included pain, redness and swelling.

Time frame: 7 days (Day 22 to Day 28) following dose 2

Number of Participants Reporting Each Solicited Systemic Event 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).

Time frame: 7 days (Day 1 to Day 7) following dose 1

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Participants received 2 doses of 750\_A vaccine formulation by intramuscular injection in the non-dominant arm.

GSK Investigational Site

Tempe, Arizona, United States

GSK Investigational Site

Chula Vista, California, United States

GSK Investigational Site

Long Beach, California, United States

GSK Investigational Site

Santa Ana, California, United States

GSK Investigational Site

Pembroke Pines, Florida, United States

GSK Investigational Site

Chamblee, Georgia, United States

GSK Investigational Site

Meridian, Idaho, United States

GSK Investigational Site

El Dorado, Kansas, United States

...and 10 more locations

Number of Participants Reporting Each Solicited Systemic Event Following Dose 2

Time frame: 7 days (Day 22 to Day 28) following dose 2

Number of Participants With Any Increase in Toxicity Grading in Hematological Laboratory Parameters 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).

Time frame: 7 days (Day 1 to Day 7) following dose 1

Number of Participants With Any Increase in Toxicity Grading in Hematological Laboratory Parameters 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).

Time frame: 7 days (Day 22 to Day 28) following dose 2

Number of Participants With Any Increase in Toxicity Grading in Biochemical Laboratory Parameters 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).

Time frame: 7 days (Day 1 to Day 7) following dose 1

Number of Participants With Any Increase in Toxicity Grading in Biochemical Laboratory Parameters 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).

Time frame: 7 days (Day 22 to Day 28) following dose 2

Number of Participants Reporting Unsolicited AEs 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.

Time frame: 21 days (Day 1 to Day 22) following dose 1

Number of Participants Reporting Unsolicited AEs Following Dose 2

Time frame: 21 days (Day 22 to Day 43) following dose 2

Number of Participants Reporting Unsolicited Medically Attended Adverse Events (MAEs) 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).

Time frame: 21 days (Day 1 to Day 22) following dose 1

Number of Participants Reporting Unsolicited MAEs Following Dose 2

Time frame: 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)

Time frame: Up to 6 months post dose 2 (administered on Day 22)

Number of Participants Reporting Serious Adverse Events (SAEs) up 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.

Time frame: From Day 1 to Day 43

Number of Participants Reporting SAEs up to 6 Months Post Dose 2 (Administered on Day 22)

Time frame: 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

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.

Time frame: From Day 1 to Day 43

Number of Participants Reporting pIMDs up to 6 Months Post Dose 2 (Administered on Day 22)

Time frame: Day 1 to 6 months post dose 2 (administered on Day 22)

Secondary Outcomes

HI Antibody Titers Against Vaccine-homologous H5N8

Antibody titers were presented as geometric mean titers (GMTs).

Time frame: Day 1, Day 22, and 6 months post dose 2 (administered on Day 22)

GMFR of Serum HI Antibody Titers Against Vaccine-homologous H5N8

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.

Time frame: At Day 22, and 6 months post dose 2 (administered on Day 22)

Number of Seroprotected Participants for HI Antibody Titers

Seroprotection rate is defined as the number of participants with HI titer value \>= 1:40 which is considered as indicating protection.

Time frame: At Day 1, Day 22, and 6 months post dose 2 (administered on Day 22)

Number of Seroconverted Participants for HI Antibody Titers

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.

Time frame: At Day 22, Day 43 and 6 months post dose 2 (administered on Day 22)

Microneutralization (MN) Antibody Titers for a Subset of Participants

Microneutralization testing was performed on 50% of the participants, randomly selected and equally distributed across the different age groups.

Time frame: At Day 1, Day 22, and 6 months post dose 2 (administered on Day 22)

Number of Seropositive Participants for MN Antibody Titers for a Subset of Participants

A seropositive participant is a participant whose antibody titer is greater than or equal to the assay cut-off value of 1:40.

Time frame: At Day 1, Day 22, and 6 months post dose 2 (administered on Day 22)

Number of Participants Meeting Vaccine Response (VR) Criteria of MN Antibody Titers for a Subset of Participants

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.

Time frame: At Day 22, Day 43, and 6 months post dose 2 (administered on Day 22)