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
Overview
- Phase
- Phase 1
- Intervention
- RSV (GSK3389245A) lower dose formulation vaccine
- Conditions
- Respiratory Syncytial Virus Infections
- Sponsor
- GlaxoSmithKline
- Enrollment
- 201
- Locations
- 1
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
RSV1D Pooled Group
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.
Intervention: RSV (GSK3389245A) lower dose formulation vaccine
RSV1D Pooled Group
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.
Intervention: GSK's multicomponent meningococcal B vaccine
RSV1D Pooled Group
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.
Intervention: Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine
RSV1D Pooled Group
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.
Intervention: GSK's pneumococcal polysaccharide conjugate vaccine
RSV1D Pooled Group
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.
Intervention: GSK's meningococcal group A, C, W-135 and Y conjugate vaccine
RSV1D Pooled Group
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.
Intervention: Placebo
RSV2D Pooled Group
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.
Intervention: RSV (GSK3389245A) higher dose formulation vaccine
RSV2D Pooled Group
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.
Intervention: GSK's multicomponent meningococcal B vaccine
RSV2D Pooled Group
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.
Intervention: Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine
RSV2D Pooled Group
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.
Intervention: GSK's pneumococcal polysaccharide conjugate vaccine
RSV2D Pooled Group
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.
Intervention: GSK's meningococcal group A, C, W-135 and Y conjugate vaccine
Comparator_Placebo Pooled Group
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).
Intervention: GSK's multicomponent meningococcal B vaccine
Comparator_Placebo Pooled Group
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).
Intervention: Pfizer's meningococcal group A, C, W-135 and Y conjugate vaccine
Comparator_Placebo Pooled Group
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).
Intervention: GSK's pneumococcal polysaccharide conjugate vaccine
Comparator_Placebo Pooled Group
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).
Intervention: GSK's meningococcal group A, C, W-135 and Y conjugate vaccine
Comparator_Placebo Pooled Group
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).
Intervention: Placebo
Outcomes
Primary Outcomes
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)
Time Frame: 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.
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)
Time Frame: 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.
Number of Subjects With Any Solicited General AEs During a 7-day Follow-up Period After the First Vaccination (Administered at Day 1)
Time Frame: 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.
Number of Subjects With Any Solicited General AEs During a 7-day Follow-up Period After the Second Vaccination (Administered at Day 31)
Time Frame: 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.
Number of Subjects With Episode of Spontaneous or Excessive Bleeding (AE of Special Interest)
Time Frame: During a 30-day follow-up period across the 2 vaccinations administered at Day 1 and Day 31
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.
Number of Subjects With Any Unsolicited AEs
Time Frame: During a 30-day follow-up period across the 2 vaccinations administered at Day 1 and Day 31
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.
Number of Subjects With Any Serious Adverse Events (SAEs) From Day 1 up to Day 61
Time Frame: 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.
Secondary Outcomes
- Number of Subjects With RSV-RTI, RSV-LRTI, Severe RSV-LRTI and Very Severe RSV-LRTI (According to Standardized Case Definitions)(From first vaccination (Day 1) up to the end of the second RSV transmission season (up to 2 years))
- 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)(From first vaccination (Day 1) up to the end of the first RSV transmission season (up to 1 year))
- Number of Subjects With SAEs From First Vaccination (Day 1) up to the End of the Second RSV Transmission Season (up to 2 Years)(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)(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)(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)(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(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(At pre-vaccination (Screening), Day 31, Day 61 and at the end of the first RSV transmission season (EOS1) (up to 1 year))