A Study to Test GlaxoSmithKline's (GSK) Respiratory Syncytial Virus RSV Candidate Vaccine's Safety and Immune Response in Japanese Older Adults

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, reactogenicity and immunogenicity of 2 doses of GSK Biologicals' RSV candidate vaccine adjuvanted with AS01B for the prevention of lower respiratory tract diseases caused by RSV in ethnic Japanese adults 60-80 years of age.

Official Title
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Phase I, Observer-blind, Safety, Reactogenicity and Immunogenicity Study of GSK's Respiratory Syncytial Virus (RSV) Vaccine GSK3844766A in Japanese Subjects Aged 60-80 Years

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: RSV_PreF3 Vaccine (GSK3844766A) adjuvanted with AS01B
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol. Written informed consent obtained from the subject prior to performance of any study specific procedure. A male or female between, and including, 60 and 80 years of age at the time of the first vaccination. Subjects with residence status allowing free mixing with general community or in an assisted-living facility that provides minimal assistance, such that the subject is primarily responsible for self-care and activities of daily living, may be enrolled. Japanese ethnic origin (defined as having been born in Japan with four ethnic Japanese grandparents and able to speak Japanese). Subject satisfying screening requirements. Exclusion Criteria: Medical conditions Any medical condition that in the judgment of the investigator would make IM injection unsafe. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Hypersensitivity to latex. Serious or unstable chronic illness. Patients with chronic stable conditions with or without specific treatment, such as diabetes, hypertension or cardiac disease, are allowed to participate in this study. Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study. History of any neurological disorders or seizures. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by the investigator based on medical history, physical examination or laboratory screening tests. Hepatomegaly, right upper quadrant abdominal pain or tenderness. Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study. Lymphoproliferative disorder and malignancy within 5 years. At screening: Hematology parameters (complete blood cell count [red blood cells, WBC], white blood cells differential count [lymphocytes, neutrophils and eosinophils], platelets count or hemoglobin level) and/or biochemistry parameters (creatinine, blood urea nitrogen or liver enzymes [ALT or AST]) outside the normal laboratory ranges, unless the laboratory abnormalities are considered not clinically significant by the investigator. Prior/Concomitant therapy Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine during the period starting 30 days before the first dose of study vaccine (Day -29 to Day 1), or planned use during the study period. Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of study vaccine administration, with the exception of inactivated and subunit influenza vaccines which can be administered up to 14 days before or from 30 days after each study vaccination. Previous vaccination with an RSV vaccine. Known previous administration of a vaccine containing MPL, QS-21 and/or MF59. Planned administration of GSK's Herpes Zoster vaccine marketed as Shingrix or an adjuvanted recombinant varicella zoster virus envelope gE subunit vaccine [HZ/su] within 180 days after the second dose of the study vaccine. Chronic administration (defined as more than 14 consecutive days in total) of immunosuppressants or other immune-modifying drugs during the period starting 6 months prior to the first vaccine dose. For corticosteroids, this will mean prednisone (≥ 20 mg/day, or equivalent). Inhaled and topical steroids are allowed. Administration of long-acting immune-modifying drugs or planned administration at any time during the study period. Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccine or planned administration during the study period. Prior/Concurrent clinical study experience • Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device). Other exclusions History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. Body mass index greater than 40 kg/m^2. Planned move to a location that will prohibit participating in the trial until study end. Bedridden subjects.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 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 |
| --- | --- |
| Experimental: RSV_PreF3_AS01B Group<br>Subjects aged 60 to 80 years received 2 doses of the investigational adjuvanted RSV_PreF3 vaccine (GSK3844766A), at Day 1 and Day 61, by intramuscular (IM) injection into the deltoid region of the non-dominant arm preferably. | Biological: RSV_PreF3 Vaccine (GSK3844766A) adjuvanted with AS01B<br>* Subjects aged 60 to 80 years received 2 doses of the investigational adjuvanted RSV_PreF3 vaccine (GSK3844766A), at Day 1 and Day 61, by intramuscular (IM) injection into the deltoid region of the non-dominant arm preferably.<br>|
| Placebo Comparator: Placebo Group<br>Subjects aged 60 to 80 years received 2 doses of placebo as control, at Day 1 and Day 61, by IM injection into the deltoid region of the non-dominant arm preferably. | Drug: Placebo<br>* Subjects aged 60 to 80 years received 2 doses of placebo as control, at Day 1 and Day 61, by IM injection into the deltoid region of the non-dominant arm preferably.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Solicited Local Adverse Events (AEs) After First Dose of Vaccination | Assessed solicited local AEs at injection site are pain, erythema and swelling. Any erythema/swelling is scored with a diameter larger than (>) 20 millimeters (mm). | During a 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after first dose of vaccination administered at Day 1 | 
| Number of Subjects With Solicited Local AEs After Second Dose of Vaccination | Assessed solicited local AEs at injection site are pain, erythema and swelling. Any erythema/swelling was scored with a diameter larger than (>) 20 millimeters (mm). | During a 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after second dose of vaccination administered at Day 61 | 
| Number of Subjects With Solicited General AEs After First Dose of Vaccination | Assessed solicited general AEs solicited were: arthralgia; fatigue; fever (any temperature greater than or equal to 38.0 °C - the preferred location for measuring temperature being the oral cavity); gastrointestinal symptoms (including nausea, vomiting, diarrhea and/or abdominal pain); headache; myalgia and shivering. | During a 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after first dose of vaccination administered at Day 1 | 
| Number of Subjects With Solicited General AEs After Second Dose of Vaccination | Assessed solicited general AEs solicited are: arthralgia; fatigue; fever (any temperature greater than or equal to 38.0 °C - the preferred location for measuring temperature being the oral cavity); gastrointestinal symptoms including (nausea, vomiting, diarrhea and/or abdominal pain); headache; myalgia and shivering. | During a 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after second dose of vaccination administered at Day 61 | 
| Number of Subjects With Unsolicited AEs After Any Vaccination | An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. | During a 30-day follow-up period (i.e., on the day of vaccination and 29 subsequent days) after any vaccination (across doses) | 
| Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After First Vaccine Dose When Compared to Day 1 | Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, white blood cells. Biochemical laboratory parameters include alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, urea nitrogen and uric acid. Categories reported when comparing Day 1 (pre-vaccination dose 1=baseline) and Day 8 hematological and biochemical laboratory results are defined as follows: <parameter>-<range at baseline>-<range at timing> (e.g. ALT-Within-Within). Ranges level being classified as below, within or above the normal ranges. | At 7 days after the first vaccine dose (i.e. at Day 8 versus Day 1) | 
| Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After Second Vaccine Dose When Compared to Day 61 | Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, white blood cells. Biochemical laboratory parameters include alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, urea nitrogen and uric acid. Categories reported when comparing Day 61 (pre-vaccination dose 2=baseline) and Day 68 hematological and biochemical laboratory results are defined as follows: <parameter>-<range at baseline>-<range at timing> (e.g. ALT-Within-Within). Ranges level being classified as below, within or above the normal ranges. | At 7 days after the second vaccine dose (i.e at Day 68 versus Day 61) | 
| Number of Subjects With Any Grade 3 Non-serious AEs (Solicited and Unsolicited) After First Dose of Vaccination | A Grade 3 AE is any AE assessed as severe, i.e. which prevents normal, everyday activities. In adults, such an AE would, for example, prevent attendance at work and would necessitate the administration of corrective therapy. | During a 30-day follow-up period (i.e., on the day of vaccination at Day 1, and 29 subsequent days) after first vaccination | 
| Number of Subjects With Any Grade 3 Non-serious AEs (Solicited and Unsolicited) After Second Dose of Vaccination | A Grade 3 AE is any AE assessed as severe, i.e. which prevents normal, everyday activities. In adults, such an AE would, for example, prevent attendance at work and would necessitate the administration of corrective therapy. | During a 30-day follow-up period (i.e., on the day of vaccination at Day 61, and 29 subsequent days) after second vaccination | 
| Number of Subjects With Any Serious Adverse Events (SAEs) up to 30 Days After the Second Vaccination | A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. | From Day 1 up to 30 days after the second vaccination (Day 91) | 
| Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs) up to 30 Days After the Second Vaccination | pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology | From Day 1 up to 30 days after the second vaccination (Day 91) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral Immune Response With Respect to Components of the Investigational Vaccine in Terms of Neutralizing Antibody Titers Against RSV- Serotype A | Serological assays for the determination of functional antibodies against RSV-A were performed by neutralization assay. Anti RSV-A neutralizing antibody titers are given as geometric mean titers (GMTs) and expressed as Estimated Dose: serum dilution giving a 60% reduction of the signal compared to a control without serum (ED60). The cut-off of the assay is 18 ED60. | At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91) | 
| Humoral Immune Response With Respect to Components of the Investigational Vaccine in Terms of RSVPreF3-specific Immunoglobulin G (IgG) Antibody Concentrations | The detection and the quantification of total IgG antibodies directed against RSVPreF3 in human serum samples are based on an indirect enzyme-linked immunosorbent assay (ELISA). Anti RSVPreF3 antibody concentration is given in geometric mean concentration (GMC) and is expressed in ELISA Laboratory Units per milliliter (ELU/mL). The assay cut-off is 25 ELU/mL. | At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91) | 
| Number of Subjects With Any SAEs, up the End of Follow-up Study Period (Month 14) | A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. | From Day 1 up to the end of follow-up period (Month 14) | 
| Number of Subjects Reporting pIMDs up to the End of Follow-up Study Period (Month 14) | pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. | From Day 1 up to the end of follow-up period (Month 14) | 
| Number of Subjects With Respiratory Tract Infection (RTI) Episodes Reported During RTI Surveillance | The number of RTI cases is provided by group. Reported categories are RSV+ RTI (= RTI episode tested as RSV positive by quantitative reverse transcription polymerase chain reaction (qRT-PCR) on nasal/throat swab collected at assessment visit) and RSV- RTI (= RTI episode tested as RSV negative by qRT-PCR on nasal/throat swab collected at assessment visit). | During the RSV seasons from Day 1 to Month 14 |