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

Study Overview
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Brief Summary
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Study to evaluate the safety and immunogenicity of H7N9 antigen in combination with full or half doses of AS03 adjuvant system in healthy adults.

Official Title
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A Phase I/II Observer-blind, Randomized, Placebo-controlled, Multi-center Trial to Evaluate the Safety and Immunogenicity of Different Formulations of Monovalent Influenza A/Hong Kong/125/2017-like (H7N9) Virus Vaccine With AS03 Adjuvant System, Given as a Two-dose Series to Adults 18 to 64 Years of Age and 65 Years of Age and Older

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: FLU-Q-PAN H7N9 Formulation 1
* Biological: FLU-Q-PAN H7N9 Formulation 2
* Biological: FLU-Q-PAN H7N9 Formulation 3
* Biological: AS03B
* Biological: AS03A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy 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 first vaccination. Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards and COVID-19 assessment card, return for follow-up visits, or return the diary cards and COVID-19 assessment card in a timely manner using the pre stamped envelope received at the site). Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study specific procedure. Female participants of non-childbearing potential may be enrolled in the study. Non childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion hysterectomy, bilateral ovariectomy or post-menopause. Female participants of childbearing potential may be enrolled in the study, if the participant: has practiced adequate contraception for 1 month prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series. Exclusion Criteria: Current diagnosis or history of autoimmune disorder(s). History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Hypersensitivity to latex. Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality that appears uncontrolled, as determined by history or physical examination. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). Recurrent history or uncontrolled neurological disorders or seizures. History of Guillain-Barré syndrome. Diagnosed with narcolepsy; or history of narcolepsy in a participant's parent, sibling or child. 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 (for example, with tamoxifen) are eligible. Documented human immunodeficiency virus-positive participant. Any clinically significant* hematological laboratory abnormality. *The investigator should use his/her clinical judgement to decide which abnormalities are clinically significant. Bedridden participants. 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 (drug, vaccine or medical device) other than the study vaccine/product during the period beginning 30 days before the first dose of study vaccine/product (Day -29 to Day 1), or planned use during the study period. Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first dose of study vaccine/product or planned administration during the study period. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine/product dose. For corticosteroids, this will mean prednisone equivalent ≥ 20 mg/day. Inhaled and topical steroids are allowed. 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 (drug or medical device). 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 chronic alcohol consumption and/or drug abuse. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. Any study personnel or immediate dependents, family, or household member.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FLU-Q-PAN H7N9 Formulation 1_B Group<br>Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 1 vaccine and AS03B adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22. | Biological: FLU-Q-PAN H7N9 Formulation 1<br>* Participants received two doses of the FLU-Q-PAN H7N9 Formulation 1 vaccine by intramuscular injection in the non-dominant arm.<br>Biological: AS03B<br>* Participants received two doses of the AS03B adjuvant by intramuscular injection in the non-dominant arm.<br>|
| Active Comparator: FLU-Q-PAN H7N9 Formulation 1_A Group<br>Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 1 vaccine and AS03A adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22. | Biological: FLU-Q-PAN H7N9 Formulation 1<br>* Participants received two doses of the FLU-Q-PAN H7N9 Formulation 1 vaccine by intramuscular injection in the non-dominant arm.<br>Biological: AS03A<br>* Participants received two doses of the AS03A adjuvant by intramuscular injection in the non-dominant arm.<br>|
| Active Comparator: FLU-Q-PAN H7N9 Formulation 2_B Group<br>Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 2 vaccine and AS03B adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22. | Biological: FLU-Q-PAN H7N9 Formulation 2<br>* Participants received two doses of the FLU-Q-PAN H7N9 Formulation 2 vaccine by intramuscular injection in the non-dominant arm.<br>Biological: AS03B<br>* Participants received two doses of the AS03B adjuvant by intramuscular injection in the non-dominant arm.<br>|
| Active Comparator: FLU-Q-PAN H7N9 Formulation 2_A Group<br>Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 2 vaccine and AS03A adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22. | Biological: FLU-Q-PAN H7N9 Formulation 2<br>* Participants received two doses of the FLU-Q-PAN H7N9 Formulation 2 vaccine by intramuscular injection in the non-dominant arm.<br>Biological: AS03A<br>* Participants received two doses of the AS03A adjuvant by intramuscular injection in the non-dominant arm.<br>|
| Active Comparator: FLU-Q-PAN H7N9 Formulation 3_B Group<br>Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 3 vaccine and AS03B adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22. | Biological: FLU-Q-PAN H7N9 Formulation 3<br>* Participants received two doses of the FLU-Q-PAN H7N9 Formulation 3 vaccine by intramuscular injection in the non-dominant arm.<br>Biological: AS03B<br>* Participants received two doses of the AS03B adjuvant by intramuscular injection in the non-dominant arm.<br>|
| Active Comparator: FLU-Q-PAN H7N9 Formulation 3_A Group<br>Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 3 vaccine and AS03A adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22. | Biological: FLU-Q-PAN H7N9 Formulation 3<br>* Participants received two doses of the FLU-Q-PAN H7N9 Formulation 3 vaccine by intramuscular injection in the non-dominant arm.<br>Biological: AS03A<br>* Participants received two doses of the AS03A adjuvant by intramuscular injection in the non-dominant arm.<br>|
| Placebo Comparator: Placebo Group<br>Healthy male and female participants who received two doses of placebo, the first dose at Day 1 and the second dose at Day 22. | Drug: Placebo<br>* Participants received two doses of Placebo by intramuscular injection in the non-dominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Seroprotected Participants for Anti-hemagglutination Inhibition (HI) Antibodies Against Vaccine-homologous H7N9 | 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. | At Day 43 | 
| Percentage of Seroconverted Participants for Anti-HI Antibodies Against Vaccine-homologous H7N9 | 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. | At Day 43 | 
| Number of Participants With Any Solicited Administration Site Events | 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). | Within the 7-day follow-up period after Dose 1 | 
| Number of Participants With Any Solicited Administration Site Events | 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. | Within the 7-day follow-up period after Dose 2 | 
| Number of Participants With Any Solicited Systemic Events | 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). | Within the 7-day follow-up period after Dose 1 | 
| Number of Participants With Any Solicited Systemic Events | 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). | Within the 7-day follow-up period after Dose 2 | 
| Number of Participants With Any and Related Unsolicited Adverse Events | 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. | Within the 21-day follow-up period after Dose 1 | 
| Number of Participants With Any and Related Unsolicited Adverse Events | 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. | Within the 21-day follow-up period after Dose 2 | 
| Number of Participants With Any and Related Medically Attended Adverse Events (MAEs) | 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. | Within the 21-day follow-up period after Dose 1 | 
| Number of Participants With Any and Related MAEs | 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. | Within the 21-day follow-up period after Dose 2 | 
| Number of Participants With Any and Related Serious Adverse Events (SAEs) | 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. | From Day 1 up to Day 43 | 
| Number of Participants With Any and Related Potential Immune Mediated Diseases (pIMDs) | 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. | From Day 1 up to Day 43 | 
| Number of Participants With Any pIMDs | 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. | From Day 1 up to Month 13 | 
| Number of Participants With Any SAEs | 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. | From Day 1 up to Month 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HI Antibody Titers Against Vaccine-homologous H7N9 | 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. | At Day 1, Day 22 and Day 43 | 
| Percentage of Seropositive Participants for HI Antibodies Against Vaccine-homologous H7N9 | 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. | At Day 1, Day 22 and Day 43 | 
| Percentage of Seroconverted Participants for HI Antibodies Against Vaccine-homologous H7N9 | 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. | At Day 22 | 
| Percentage of Seroprotected Participants for HI Antibodies Against Vaccine-homologous H7N9 | 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. | At Day 1 and Day 22 | 
| Mean Geometric Increase (MGI) of HI Antibody Titers Against Vaccine-homologous H7N9 | 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. | At Day 22 (post-Dose 1/pre-vaccination) and Day 43 (post-Dose 2/pre-vaccination) | 
| Anti-microneutralization (MN) Antibody Titers Against Vaccine-homologous H7N9 for a Subset of Participants | 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. | At Day 1, Day 22 and Day 43 | 
| Percentage of Seropositive Participants for Vaccine-homologous H7N9 MN Antibody Titers for a Subset of Participants | 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. | At Day 1, Day 22 and Day 43 | 
| Vaccine Response Rate (VRR) of Anti-MN Antibodies Against Vaccine-homologous H7N9 for a Subset of Participants | 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. | At Day 22 and Day 43 |