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 RSV-seropositive Infants

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 the respiratory syncytial virus (RSV) candidate vaccine when first administered via intramuscular (IM) injection according to a 0, 1-month schedule to RSV-seropositive infants aged 12 to 23 months.

Detailed Description
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The RSV PED-002 study, designed to evaluate the safety, reactogenicity and immunogenicity of the RSV candidate vaccine when administered in 3 sequential doses to seropositive infants aged 12 to 23 months, will be conducted in an observer-blind manner in Epoch 1 and single-blinded in Epoch 2.

Official Title
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A Phase 1/2, Randomized, Observer-blind, Controlled, Multi-center, Dose-escalation Study to Evaluate Safety, Reactogenicity and Immunogenicity of GSK Biologicals' Respiratory Syncytial Virus (RSV) Investigational Vaccine Based on the RSV Viral Proteins F, N and M2-1 Encoded by Chimpanzee-derived Adenovector (ChAd155-RSV) (GSK3389245A), When Administered Intramuscularly According to a 0, 1-month Schedule to RSV-seropositive Infants Aged 12 to 23 Months

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: RSV (GSK3389245A) low dose formulation vaccine
* Biological: RSV (GSK3389245A) middle dose formulation vaccine
* Biological: RSV (GSK3389245A) high dose formulation 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 performance of any study specific procedure. A male or female between, and including, 12 and 23 months at the time of the first vaccination. Healthy subjects as established by medical history and clinical examination before entering into the study. Seropositive for RSV as determined by IBL International kit. Born full-term (i.e. after a gestation period of 37 to less than 42 completed weeks) with a minimum birth weight of 2.5 kg. (Required for Spain) 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 0), or planned use during the study period. Any medical condition that in the judgment of the investigator would make IM injection unsafe. 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, 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 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 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. Serious chronic illness. Major congenital defects. History of any neurological disorders or seizures. History of or current autoimmune disease. History of recurrent wheezing. History of chronic cough. Previous hospitalization for respiratory illnesses. History of thrombocytopenia. History of anemia. Previous, current or planned administration of Synagis. Neurological complications following any prior vaccination. Born to a mother known or suspected to be 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 likely to be exacerbated by any component of the vaccine. Hypersensitivity to latex. Current severe eczema. Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal route. The preferred route for recording temperature in this study will be axillary. Clinically significant upper respiratory tract infection Subjects with a minor illness without fever may, be enrolled at the discretion of the investigator. Any clinically significant Grade 1 or any ≥ Grade 2 hematological or biochemical laboratory abnormality detected at the last screening blood sampling. Any other conditions that the investigator judges may interfere with study procedures or 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. 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. Planned move to a location that will prohibit participating in the trial until study end.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 23 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: RSV LD Group<br>RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of the RSV low dose (LD) vaccine, administered intramuscularly, one each at Day 1 and Day 31. | Biological: RSV (GSK3389245A) low dose formulation vaccine<br>* 2 doses of 0.5 ml each of RSV (GSK3389245A) low dose formulation vaccine administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.<br>|
| Experimental: RSV MD Group<br>RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.15 mL each) of the RSV middle dose (MD) vaccine, administered intramuscularly, one each at Day 1 and Day 31. | Biological: RSV (GSK3389245A) middle dose formulation vaccine<br>* 2 doses of 0.15 ml each of RSV (GSK3389245A) middle dose formulation vaccine administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.<br>|
| Experimental: RSV HD Group<br>RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of the RSV high dose (HD) vaccine, administered intramuscularly, one each at Day 1 and Day 31. | Biological: RSV (GSK3389245A) high dose formulation vaccine<br>* 2 doses of 0.5 ml each of RSV (GSK3389245A) high dose formulation vaccine administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.<br>|
| Placebo Comparator: Placebo LD group<br>RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31. | Drug: Placebo<br>* 2 doses (0.5 mL each for Placebo LD and Placebo HD groups and 0.15 mL each for Placebo MD group) of Placebo administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.<br>|
| Placebo Comparator: Placebo MD group<br>RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.15 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31. | Drug: Placebo<br>* 2 doses (0.5 mL each for Placebo LD and Placebo HD groups and 0.15 mL each for Placebo MD group) of Placebo administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.<br>|
| Placebo Comparator: Placebo HD group<br>RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31. | Drug: Placebo<br>* 2 doses (0.5 mL each for Placebo LD and Placebo HD groups and 0.15 mL each for Placebo MD group) of Placebo administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.<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) | Assessed solicited local symptoms are pain, redness and swelling at injection site. Any = occurrence of the symptom regardless of intensity grade. Any redness and swelling symptom = symptom reported with a surface diameter greater than 0 millimeters. | During a 7-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and Day 31) | 
| Number of Subjects With Any Solicited General AEs | Assessed solicited general symptoms are drowsiness, fever [defined as temperature equal to or above (≥) 37.5 degrees Celsius (°C)/99.5 degrees Fahrenheit (°F) for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal route, the preferred route for recording temperature in this study being axillary], irritability/fussiness and loss of appetite. Any = occurrence of the symptom regardless of intensity grade or relation to study vaccination. | During a 7-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and 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 is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to study vaccination. | During a 30-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and Day 31) | 
| Number of Subjects With Any Serious Adverse Events (SAEs) From Day 1 up to Day 61 | Assessed SAEs include any untoward 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. | From Day 1 up to Day 61 | 
| Number of Subjects With Episode of Spontaneous or Excessive Bleeding (AE of Specific 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 specific interest. | During a 30-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and Day 31) | 
| Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 2 | Assessed hematological laboratory parameters include hemoglobin level [HgL] white blood cells [WBC] and platelet count [PLC]. Hematological abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Unknown, Below, Within or Above. [e.g. HgL, Below, Below = HgL below normal ranges at baseline versus below normal ranges at Day 2]. | At Day 2 | 
| Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 8 | Assessed hematological laboratory parameters include hemoglobin level [HgL] white blood cells [WBC] and platelet count [PLC]. Hematological abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Below, Within or Above. [e.g. HgL, Below, Below = HgL below normal ranges at baseline versus below normal ranges at Day 8]. | At Day 8 | 
| Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 31 | Assessed hematological laboratory parameters include hemoglobin level [HgL] white blood cells [WBC] and platelet count [PLC]. Hematological abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Unknown, Below, Within or Above. [e.g. HgL, Below, Below = HgL below normal ranges at baseline versus below normal ranges at Day 31]. | At Day 31 | 
| Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 32 | Assessed hematological laboratory parameters include hemoglobin level [HgL] white blood cells [WBC] and platelet count [PLC]. Hematological abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Unknown, Below, Within or Above. [e.g. HgL, Below, Below = HgL below normal ranges at baseline versus below normal ranges at Day 32]. | At Day 32 | 
| Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 38 | Assessed hematological laboratory parameters include hemoglobin level [HgL] white blood cells [WBC] and platelet count [PLC]. Hematological abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Below, Within or Above. [e.g. HgL, Below, Below = HgL below normal ranges at baseline versus below normal ranges at Day 38]. | At Day 38 | 
| Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 61 | Assessed hematological laboratory parameters include hemoglobin level [HgL] white blood cells [WBC] and platelet count [PLC]. Hematological abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Unknown, Below, Within or Above. [e.g. HgL, Below, Below = HgL below normal ranges at baseline versus below normal ranges at Day 61]. | At Day 61 | 
| Number of Subjects With Biochemical Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 31 | Assessed biochemical laboratory parameters include alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. Biochemical abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Unknown, Below, Within or Above. [e.g. ALT, Below, Below = ALT below normal ranges at baseline versus below normal ranges at Day 31]. | At Day 31 | 
| Number of Subjects With Biochemical Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 61 | Assessed biochemical laboratory parameters include alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. Biochemical abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Below, Within or Above. [e.g. ALT, Below, Below = ALT below normal ranges at baseline versus below normal ranges at Day 61]. | At Day 61 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any SAEs From Day 1 up to Day 366 | Assessed SAEs include any untoward 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. | From Day 1 up to Day 366 | 
| Number of Subjects With Lower Respiratory Tract Infection Associated With RSV Infection (RSV-LRTI) (AE of Specific Interest) From Dose 1 Administration (Day 1) up to Day 366 | Subjects experiencing an LRTI associated with RSV infection were reported as AE of specific 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. | From Dose 1 administration (Day 1) up to Day 366 | 
| Number of Subjects With Respiratory Tract Infection Associated With RSV Infection (RSV-RTI), RSV-LRTI, Severe RSV-LRTI (According to Standardized Case Definitions) From Dose 1 Administration (Day 1) up to Day 366 | RSV-RTI refers to subject having runny nose OR blocked nose OR cough AND confirmed RSV infection [RSV infection confirmed on nasal swab positive for RSV A or B by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) performed at sponsor level]. RSV-LRTI refers to subject with history of cough OR difficulty breathing [based on history reported by parents/legally acceptable representatives (LARs) and includes difficulty breathing (e.g. showing signs of wheezing or stridor, tachypnoea, flaring of nostrils, chest in-drawing, apnoea) associated with nasal obstruction] AND Blood Oxygen Saturation (SpO2) lower than (<) 95 percent (%), OR respiratory rate (RR) increase [defined as ≥ 40/minute (12 months of age or above)] AND confirmed RSV infection. RSV-severe LRTI are cases meeting the case definition of RSV-LRTI AND SpO2 < 93%, OR lower chest wall in-drawing. | From Dose 1 administration (Day 1) up to Day 366 | 
| Number of Subjects With Any SAEs From Day 1 up to Study Conclusion at Day 731 | Assessed SAEs include any untoward 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. | From Day 1 up to study conclusion at Day 731 | 
| Number of Subjects With RSV-LRTI (AE of Specific Interest) From Dose 1 Administration (Day 1) up to Study Conclusion at Day 731 | Subjects experiencing an LRTI associated with RSV infection were reported as AE of specific 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. | From Dose 1 administration (Day 1) up to study conclusion at Day 731 | 
| Number of Subjects With RSV-RTI, RSV-LRTI, Severe RSV-LRTI (According to Standardized Case Definitions) From Dose 1 Administration (Day 1) up to Study Conclusion at Day 731 | RSV-RTI refers to subject having runny nose OR blocked nose OR cough AND confirmed RSV infection (RSV infection confirmed on nasal swab positive for RSV A or B by qRT-PCR performed at sponsor level). RSV-LRTI refers to subject with history of cough OR difficulty breathing [based on history reported by parents/LARs and includes difficulty breathing (e.g. showing signs of wheezing or stridor, tachypnoea, flaring of nostrils, chest in-drawing, apnoea) associated with nasal obstruction] AND Sp02 < 95% OR respiratory rate (RR) increase [defined as ≥ 40/minute (12 months of age or above)] AND confirmed RSV infection. RSV-severe LRTI are cases meeting the case definition of RSV-LRTI AND SpO2 < 93%, OR lower chest wall in-drawing. | From Dose 1 administration (Day 1) up to study conclusion at Day 731 | 
| Frequency of RSV-specific CD4+ T-cells Expressing at Least Two Markers Upon Stimulation With F, N and M2-1 Peptide Pools | Magnitude of cell mediated immunity (CMI) response to the investigational RSV vaccine was measured in terms of frequency of RSV-specific CD4+ T-cells expressing at least two markers upon stimulation with F, N and M2-1 peptide pools and expressed in RSV-specific CD4+ T-cells/million cells. Assessed markers were CD40-L, IL-2, TNF-α and IFN-ɣ. | At Pre-vaccination (Screening), Day 31, Day 61 and Day 366 | 
| 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. | At Pre-vaccination (Screening), Day 31, Day 61 and Day 366 | 
| Anti-RSV-F Antibody Concentrations | Humoral response to the investigational RSV vaccine was measured as anti-RSV F antibody concentrations and expressed as geometric mean concentrations (GMCs) in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL). | At Pre-vaccination (Screening), Day 31, Day 61 and Day 366 | 
| Palivizumab-competing Antibody Concentrations | Humoral response to the investigational RSV vaccine was measured as Palivizumab-competing antibody concentrations and expressed as geometric mean concentrations (GMCs) in microgram/milliliter (µg/mL). | At Pre-vaccination (Screening), Day 31 and Day 61 | 

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