Respiratory Syncytial Virus (RSV) Investigational Vaccine in Infants Aged 6 and 7 Months Likely to be Unexposed to RSV

Study Overview
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Brief Summary
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The purpose of this study is to provide critical information on the safety, reactogenicity and immunogenicity profile of the investigational recombinant chimpanzee adenovirus Type 155-vectored RSV (ChAd155-RSV) vaccine in infants likely to be unexposed to RSV and will assess a single lower dose and a higher two dose regimen, before moving to future studies. This study will also assess if there is a risk of 'vaccine-induced enhanced RSV disease' after vaccination of these infants with the ChAd155-RSV vaccine.

Official Title
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A Study to Evaluate Safety, Reactogenicity and Immunogenicity of GSK Biologicals' RSV Investigational Vaccine Based on Viral Proteins Encoded by Chimpanzee-derived Adenovector (ChAd155-RSV) (GSK3389245A) in Infants

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: RSV (GSK3389245A) lower dose formulation vaccine
* Biological: RSV (GSK3389245A) higher dose formulation vaccine
* Biological: GSK's multicomponent meningococcal B vaccine
* Biological: Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine
* Biological: GSK's pneumococcal polysaccharide conjugate vaccine
* Biological: GSK's meningococcal group A, C, W-135 and Y conjugate vaccine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects' parent(s)/Legally Acceptable Representative [LAR(s)] who, in the opinion of the investigator, can and will comply with the requirements of the protocol Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure. A male or female between and including 6 and 7 months of age (from the day the infant becomes 6 months of age until the day before the infant achieves 8 months of age) at the time of the first vaccination. Healthy subjects as established by medical history and clinical examination before entering into the study. Born full-term with a minimum birth weight of 2.5 kilograms (kg). Subjects' parent(s)/LAR(s) need to have access to a consistent mean of telephone contact or computer. Exclusion Criteria: Child in care Use of any investigational or non-registered product 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. Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine. For corticosteroids, this will mean prednisone ≥ 0.5 milligrams (mg)/kg/day (for pediatric subjects), or equivalent. 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 three months before the first dose of study vaccine or planned administration 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 vaccine administration, with the exception of scheduled routine pediatric vaccines. Scheduled routine pediatric vaccines may be administered ≥ 7 days before a dose of study vaccine or ≥ 7 days following a dose of study vaccine, with the exception of live viral vaccines which may be administered ≥ 14 days before a dose or ≥ 7 days after a dose. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. A history of, or on-going confirmed RSV disease or highly compatible clinical picture. Serious chronic illness. Major congenital defects. History of any neurological disorders or seizures. History of or current autoimmune disease. History of recurrent wheezing in the subject's lifetime. History of chronic cough. Previous hospitalization for lower respiratory illnesses. Previous, current or planned administration of Synagis (palivizumab). Neurological complications following any prior vaccination. Born to a mother known or suspected to be Human Immunodeficiency Virus (HIV)-positive . Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination . Family history of congenital or hereditary immunodeficiency. Previous vaccination with a recombinant simian or human adenoviral vaccine. History of any reaction or hypersensitivity to any component of the vaccines (investigational or control) or placebo used in this study or any contraindication to them. Hypersensitivity to latex. Current severe eczema. Acute disease and/or fever at the time of enrolment (Visit 1). Any clinically significant Grade 1 or any ≥ Grade 2 hematological or biochemical laboratory abnormality detected at the last screening blood sampling. Any medical condition that in the judgment of the investigator would make intramuscular (IM) injection unsafe. Any other conditions that the investigator judges may interfere with study procedures, findings. Any conditions that could constitute a risk for the subjects while participating to this study. Weight below the fifth percentile of the local weight-for-age curve according to the World Health Organization (WHO) weight- for- age tables. Participating in another clinical study, at any time during the study period, in which the subject or mother (if breastfeeding) has been or will be exposed to an investigational or a non-investigational vaccine/product. Planned move to a location that will prohibit participating in the trial until study end. For Thailand only, subjects who have received Synflorix prior to enrolment.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 7 Months

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: RSV1D Pooled Group<br>Subjects received the interventions as follows: Either 1 dose of experimental RSV (GSK3389245A) lower dose formulation at Day 1, followed by 1 dose of Placebo at Day 31 and any one the following active comparators: 2 doses of GSK's meningococcal group A, C, W-135 and Y conjugate vaccine (administered at Day 61 and at the end of RSV season 1) or 3 doses of GSK's multicomponent meningococcal B vaccine or Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine or GSK's pneumococcal polysaccharide conjugate vaccine (administered at Days 61, 121 and at the end of RSV season 1). Or 1 dose of experimental RSV (GSK3389245A) lower dose formulation at Day 1, followed by 1 dose of Placebo at Day 31. | Biological: RSV (GSK3389245A) lower dose formulation vaccine<br>* 1 dose of RSV (GSK3389245A) lower dose formulation vaccine administered intramuscularly at Day 1.<br>Biological: GSK's multicomponent meningococcal B vaccine<br>* 3 doses of GSK's multicomponent meningococcal B vaccine administered intramuscularly, at Day 61, Day 121 and at the end of RSV season 1, or at Day 1, Day 61 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Bexsero;Biological: Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine<br>* 3 doses of Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine administered intramuscularly, at Day 61, Day 121 and at the end of RSV season 1, or at Day 1, Day 61 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Nimenrix;Biological: GSK's pneumococcal polysaccharide conjugate vaccine<br>* 3 doses of GSK's pneumococcal polysaccharide conjugate vaccine administered intramuscularly, at Day 61, Day 121 and at the end of RSV season 1, or at Day 31, Day 61 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Synflorix;Biological: GSK's meningococcal group A, C, W-135 and Y conjugate vaccine<br>* 2 doses of GSK's meningococcal group A, C, W-135 and Y conjugate vaccine administered intramuscularly, at Day 61 and at the end of RSV season 1, or at Day 31 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Menveo;Drug: Placebo<br>* 1 dose or 2 doses of Placebo administered intramuscularly at Day 31, or at Day 1 and Day 31, or at Day 1 and Day 61, or at Day 31 and Day 121, depending on the vaccination schedule.<br>|
| Experimental: RSV2D Pooled Group<br>Subjects received the interventions as follows: Either 2 doses of experimental RSV (GSK3389245A) higher dose formulation (administered at Day 1 and Day 31) and followed by any one the following active comparators: 2 doses of GSK's meningococcal group A, C, W-135 and Y conjugate vaccine (administered at Day 61 and at the end of RSV season 1) or 3 doses of GSK's multicomponent meningococcal B vaccine or Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine or GSK's pneumococcal polysaccharide conjugate vaccine (administered at Days 61, 121 and at the end of RSV season 1). Or 2 doses of experimental RSV (GSK3389245A) higher dose formulation administered at Day 1 and Day 31. | Biological: RSV (GSK3389245A) higher dose formulation vaccine<br>* 2 doses of RSV (GSK3389245A) higher dose formulation vaccine administered intramuscularly, at Day 1 and Day 31.<br>Biological: GSK's multicomponent meningococcal B vaccine<br>* 3 doses of GSK's multicomponent meningococcal B vaccine administered intramuscularly, at Day 61, Day 121 and at the end of RSV season 1, or at Day 1, Day 61 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Bexsero;Biological: Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine<br>* 3 doses of Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine administered intramuscularly, at Day 61, Day 121 and at the end of RSV season 1, or at Day 1, Day 61 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Nimenrix;Biological: GSK's pneumococcal polysaccharide conjugate vaccine<br>* 3 doses of GSK's pneumococcal polysaccharide conjugate vaccine administered intramuscularly, at Day 61, Day 121 and at the end of RSV season 1, or at Day 31, Day 61 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Synflorix;Biological: GSK's meningococcal group A, C, W-135 and Y conjugate vaccine<br>* 2 doses of GSK's meningococcal group A, C, W-135 and Y conjugate vaccine administered intramuscularly, at Day 61 and at the end of RSV season 1, or at Day 31 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Menveo;|
| Active Comparator: Comparator_Placebo Pooled Group<br>Subjects received either one of interventions schedules as follows: 3 doses of GSK's multicomponent meningococcal B vaccine (administered at Days 1, 61 and at the end of RSV season 1) and 2 doses of Placebo (administered at Days 31 and 121). 3 doses of Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine (administered at Days 1, 61 and at the end of RSV season 1) and 2 doses of Placebo (administered at Days 31 and 121). 3 doses of GSK's pneumococcal polysaccharide conjugate vaccine (administered at Days 31, 61 and at the end of RSV season 1) and 2 doses of Placebo (administered at Day 1 and Day 121). 2 doses of GSK's meningococcal group A, C, W-135 and Y conjugate vaccine (administered at Day 31 and at the end of RSV season 1) and 2 doses of Placebo (administered at Days 1 and 61) . 2 doses of Placebo alone (administered at Days 1 and 31). | Biological: GSK's multicomponent meningococcal B vaccine<br>* 3 doses of GSK's multicomponent meningococcal B vaccine administered intramuscularly, at Day 61, Day 121 and at the end of RSV season 1, or at Day 1, Day 61 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Bexsero;Biological: Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine<br>* 3 doses of Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine administered intramuscularly, at Day 61, Day 121 and at the end of RSV season 1, or at Day 1, Day 61 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Nimenrix;Biological: GSK's pneumococcal polysaccharide conjugate vaccine<br>* 3 doses of GSK's pneumococcal polysaccharide conjugate vaccine administered intramuscularly, at Day 61, Day 121 and at the end of RSV season 1, or at Day 31, Day 61 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Synflorix;Biological: GSK's meningococcal group A, C, W-135 and Y conjugate vaccine<br>* 2 doses of GSK's meningococcal group A, C, W-135 and Y conjugate vaccine administered intramuscularly, at Day 61 and at the end of RSV season 1, or at Day 31 and end of RSV season 1, depending on the vaccination schedule.<br>* Other names: Menveo;Drug: Placebo<br>* 1 dose or 2 doses of Placebo administered intramuscularly at Day 31, or at Day 1 and Day 31, or at Day 1 and Day 61, or at Day 31 and Day 121, depending on the vaccination schedule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any Solicited Local Adverse Events (AEs) During a 7-day Follow-up Period After the First Vaccination (Administered at Day 1) | Assessed solicited local AEs are erythema, pain and swelling at injection site. Any = occurrence of the adverse event regardless of intensity grade. Any redness and swelling = adverse event reported with a surface diameter greater than 0 millimeters. Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, active comparators pooled and placebo groups separately to compare the expected adverse events observed from routine pediatric vaccines (active comparators) with the investigational RSV vaccine. Placebo was not pooled with active comparators as no significant difference was expected in AEs when placebo was pooled with active comparators. As pre-specified in the protocol, the choice of active comparator or placebo was based on each participating country's standard of care. | During a 7-day follow-up period after the first vaccination (administered at Day 1) | 
| Number of Subjects With Any Solicited Local Adverse Events (AEs) During a 7-day Follow-up Period After the Second Vaccination (Administered at Day 31) | Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, active comparators pooled and placebo groups separately to compare the expected adverse events observed from routine pediatric vaccines (active comparators) with the investigational RSV vaccine. Placebo was not pooled with active comparators as no significant difference was expected in AEs when placebo was pooled with active comparators. As pre-specified in the protocol, the choice of active comparator or placebo was based on each participating country's standard of care. | During a 7-day follow-up period after the second vaccination (administered at Day 31) | 
| Number of Subjects With Any Solicited General AEs During a 7-day Follow-up Period After the First Vaccination (Administered at Day 1) | Assessed solicited general adverse events are drowsiness, fever [defined as temperature equal to or above (>=) 38.degrees Celsius (C)/100.4 Fahrenheit (F) by any route], irritability/fussiness and loss of appetite. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, each of the active comparators and placebo groups separately as the study interest was to investigate solicited AEs during the follow-up period of RSV vaccine administration, compared to placebo and routine pediatric vaccines, especially comparing to the rates of Bexsero-related fever. As pre-specified in the protocol, the choice of active comparator or placebo was based on each participating country's standard of care. | During a 7-day follow-up period after the first vaccination (administered at Day 1) | 
| Number of Subjects With Any Solicited General AEs During a 7-day Follow-up Period After the Second Vaccination (Administered at Day 31) | Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, each of the active comparators and placebo groups separately as the study interest was to investigate solicited AEs during the follow-up period of RSV vaccine administration, compared to placebo and routine pediatric vaccines, especially comparing to the rates of Bexsero-related fever. As pre-specified in the protocol, the choice of active comparator or placebo was based on each participating country's standard of care. | During a 7-day follow-up period after the second vaccination (administered at Day 31) | 
| Number of Subjects With Any Unsolicited AEs | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Unsolicited AEs are 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to study vaccination. Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, and comparator_placebo pooled groups as data collection was based on different standard of care provided at participating countries rather than randomization to each of the individual groups. According to the pre-specified analysis plan, data collected for participant flow, baseline characteristics and adverse events reporting were not analyzed for the individual groups. | During a 30-day follow-up period across the 2 vaccinations administered at Day 1 and Day 31 | 
| Number of Subjects With Any Serious Adverse Events (SAEs) From Day 1 up to Day 61 | Assessed serious adverse events (SAEs) include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. Any = occurrence of SAE regardless of intensity grade or relation to study vaccination. Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, and comparator_placebo pooled groups as data collection was based on different standard of care provided at participating countries rather than randomization to each of theindividual groups. According to the pre-specified analysis plan, data collected for participant flow, baseline characteristics and adverse events reporting were not analyzed for the individual groups. | From Day 1 up to Day 61 | 
| Number of Subjects With Episode of Spontaneous or Excessive Bleeding (AE of Special Interest) | Any episode of spontaneous or excessive bleeding if occurring after vaccination was to be fully investigated with a full range of hematological tests to identify the underlying cause and reported as an AE of special interest. Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, and comparator_placebo pooled groups as data collection was based on different standard of care provided at participating countries rather than randomization to each of the individual groups. According to the pre-specified analysis plan, data collected for participant flow, baseline characteristics and adverse events reporting were not analyzed for the individual groups. | During a 30-day follow-up period across the 2 vaccinations administered at Day 1 and Day 31 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Respiratory Tract Infection Associated With RSV Infection (RSV-RTI), Lower Respiratory Tract Infection Associated With RSV Infection (RSV-LRTI), Severe RSV-LRTI and Very Severe RSV-LRTI (According to Standardized Case Definitions) | According to standardized case definitions,RSV-RTI is a subject having runny nose/blocked nose/ cough & confirmed RSV infection.RSV-LRTI is a subject having history of cough/ difficulty breathing[based on history reported by parents] & blood oxygen saturation (SpO2) lower than(<)95 percent (%)/ respiratory rate (RR) increase & confirmed RSV infection Severe RSV-LRTI-Cases meeting RSV-LRTI case definition & an SpO2<93 %/lower chest wall in-drawing. Very severe RSV-LRTI-Cases meeting RSV-LRTI case definition & an SpO2<90%/inability to feed/failure to respond/unconscious.Analysis of this outcome measure was reported for RSV1D pooled, RSV2D pooled & comparator_placebo pooled groups as data was collected based on different standard of care provided at participating countries rather than randomization to each of the groups.Per the pre-specified analysis plan,data collected for participant flow, baseline characteristics and adverse events reporting were not analyzed for the individual groups | From first vaccination (Day 1) up to the end of the first RSV transmission season (up to 1 year) | 
| Number of Subjects With RSV-RTI, RSV-LRTI, Severe RSV-LRTI and Very Severe RSV-LRTI (According to Standardized Case Definitions) | Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, and comparator_placebo pooled groups as data collection was based on different standard of care provided at participating countries rather than randomization to each of the individual groups. According to the pre-specified analysis plan, data collected for participant flow, baseline characteristics and adverse events reporting were not analyzed for the individual groups. | From first vaccination (Day 1) up to the end of the second RSV transmission season (up to 2 years) | 
| Number of Subjects With SAEs From First Vaccination (Day 1) up to the End of the Second RSV Transmission Season (up to 2 Years) | Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, and comparator_placebo pooled groups as data collection was based on different standard of care provided at participating countries rather than randomization to each of the 15 groups. According to the pre-specified analysis plan, data collected for participant flow, baseline characteristics and adverse events reporting were not analyzed for the individual groups. | From first vaccination (Day 1) up to the end of the second RSV transmission season (up to 2 years) | 
| Number of Subjects With RSV-LRTI (AE of Special Interest) From First Vaccination (Day 1) up to the End of the First RSV Transmission Season (up to 1 Year) | Subjects experiencing an LRTI associated with RSV infection were reported as AE of special interest. To identify RSV-LRTI for the purpose of AE of specific interest, the diagnosis was based on the investigators' clinical judgment taking into account the clinical history, the examination, relevant medical investigations and locally-available diagnostic test for RSV. Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, and comparator_placebo pooled groups as data collection was based on different standard of care provided at participating countries rather than randomization to each of the individual groups. According to the pre-specified analysis plan, data collected for participant flow, baseline characteristics and adverse events reporting were not analyzed for the individual groups. | From first vaccination (Day 1) up to the end of the first RSV transmission season (up to 1 year) | 
| Number of Subjects With RSV-LRTI (AE of Special Interest) From First Vaccination (Day 1) up to the End of the Second RSV Transmission Season (up to 2 Years) | Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, and comparator_placebo pooled groups as data collection was based on different standard of care provided at participating countries rather than randomization to each of the individual groups. According to the pre-specified analysis plan, data collected for participant flow, baseline characteristics and adverse events reporting were not analyzed for the individual groups. | From first vaccination (Day 1) up to the end of the second RSV transmission season (up to 2 years) | 
| Number of RSV Infected Subjects With a Negative RSV Exposure Status (at Screening Based on In-stream Baseline Serological Testing) With Very Severe RSV-LRTI (According to Standardized Case Definition) | Very severe RSV LRTI are cases meeting the case definition of RSV-LRTI AND a SpO2 <90%, OR inability to feed, OR failure to respond/unconscious. Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, and comparator_placebo pooled groups as data collection was based on different standard of care provided at participating countries rather than randomization to each of the individual groups. According to the pre-specified analysis plan, data collected for participant flow, baseline characteristics and adverse events reporting were not analyzed for the individual groups. | From first vaccination (Day 1) up to the end of the first RSV transmission season (up to 1 year) | 
| Anti-RSV-A Neutralizing Antibody Titers | Humoral response to the investigational RSV vaccine was measured in terms of anti-RSV-A neutralizing antibody titers and expressed as geometric mean titers (GMTs) in Estimated Dilution 60 (ED60) titers. Analysis of this outcome measure were reported for the RSV1D pooled, RSV2D pooled, and comparator_placebo pooled groups as data collection was based on different standard of care provided at participating countries rather than randomization to each of the individual groups. According to the pre-specified analysis plan, data collected for participant flow, baseline characteristics and adverse events reporting were not analyzed for the individual groups. | At pre-vaccination (Screening), Day 31, Day 61 and at the end of the first RSV transmission season (EOS1) (up to 1 year) | 
| Anti-RSV-F Antibody Concentrations | Humoral response to the investigational RSV vaccine was measured in terms of anti-RSV-F antibody concentrations and expressed as geometric mean concentrations (GMCs) in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL). Analysis of this outcome measure was reported for the RSV1D pooled, RSV2D pooled, and comparator_placebo pooled groups as data collection was based on different standard of care provided at participating countries rather than randomization to each of the individual groups. According to the pre-specified analysis plan, data collected for participant flow, baseline characteristics and adverse events reporting were not analyzed for the individual groups. | At pre-vaccination (Screening), Day 31, Day 61 and at the end of the first RSV transmission season (EOS1) (up to 1 year) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Respiratory syncytial virus (RSV), Vaccine, Reactogenicity, Immunogenicity, Infants