Safety, Reactogenicity and Immunogenicity Study of Different Formulations of GlaxoSmithKline (GSK) Biologicals' Investigational RSV Vaccine (GSK3003891A), in Healthy Women

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 different formulations of a single intramuscular dose of GSK Biologicals' investigational RSV vaccine, in healthy, non-pregnant women aged 18 to 45 years.

Official Title
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An Observer-blind Study to Assess the Safety, Reactogenicity and Immunogenicity of Different Formulations of GSK Biologicals' Investigational RSV Vaccine (GSK3003891A), in Healthy Women

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: RSV vaccine GSK3003895A (formulation 1)
* Biological: RSV vaccine GSK3003898A (formulation 2)
* Biological: RSV vaccine GSK3003899A (formulation 3)
* Biological: Boostrix


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 performing any study specific procedure. Non-pregnant female between, and including, 18 and 45 years of age at the time of study vaccination. Healthy subjects as established by medical history and clinical examination before entering into the study. Female subjects of non-childbearing potential may be enrolled in the study. Female subjects of childbearing potential may be enrolled in the study, if the subject: Has practiced adequate contraception for 30 days prior to study vaccination, and Has a negative pregnancy test on the day of study vaccination, and Has agreed to continue adequate contraception during the study period. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine within 30 days prior to study vaccination, or planned use during the study period. 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. Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. Planned administration/ administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after study vaccination, with the exception of any licensed influenza vaccine which may be administered ≥ 15 days before or after study vaccination. Previous experimental vaccination against RSV. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccines. History of severe allergic reaction after a previous dose of any tetanus toxoid, diphtheria toxoid, or pertussis antigen-containing vaccine or to any component of Boostrix. History of encephalopathy of unknown aetiology occurring within 7 days following a previous vaccination with pertussis-containing vaccine. History of any neurological disorders or seizures History of transient thrombocytopenia or neurological complications following a previous vaccination against diphtheria and/ or tetanus. Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to study vaccination, or planned administration during the study period. Inhaled and topical steroids are allowed. Administration of immunoglobulins and/ or any blood products within the 3 months prior to study vaccination, or planned administration during the study period. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Family history of congenital or hereditary immunodeficiency. History of or current autoimmune disease. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality. Malignancy within previous 5 years or lymphoproliferative disorder. Current alcohol and/or drug abuse. Acute disease and/ or fever at the time of enrolment. Hypersensitivity to latex. Pregnant or lactating female. Planned move to a location that will prohibit participating in the trial until study end. Any other condition that the investigator judges may interfere with study procedures or findings.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RSV vaccine formulation 1 Group<br>Subjects in this group will receive a single dose of formulation 1 of the RSV vaccine | Biological: RSV vaccine GSK3003895A (formulation 1)<br>* Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm<br>|
| Experimental: RSV vaccine formulation 2 Group<br>Subjects in this group will receive a single dose of formulation 2 of RSV vaccine | Biological: RSV vaccine GSK3003898A (formulation 2)<br>* Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm<br>|
| Experimental: RSV vaccine formulation 3 Group<br>Subjects in this group will receive a single dose of formulation 3 of RSV vaccine | Biological: RSV vaccine GSK3003899A (formulation 3)<br>* Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm<br>|
| Active Comparator: Boostrix Group<br>Subjects in this group will receive a single dose of Boostrix | Biological: Boostrix<br>* Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm<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 Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = Significant pain at rest, pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling with a maximum diameter greater than 100 millimeters (mm). | During the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects With Solicited General Symptoms | Assessed solicited general symptoms (symp.) were headache, fever [defined as oral temperature (temp.) equal to or above 37.5 degrees Celsius (°C)], fatigue, gastrointestinal (Gastro.) symptoms [nausea, vomiting, diarrhoea and/or abdominal pain]. Any = occurrence of the symptom regardless of intensity grade and relationship. Grade 3 (G3) symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects With Unsolicited Adverse Events (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 and 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 vaccination. | During the 30-Day (Days 0-29) post-vaccination period | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | From vaccination at Day 0, up to Day 30 post-vaccination | 
| Titres of RSV-A Neutralizing Antibodies | RSV-A neutralizing antibody titres, expressed as Geometric Mean Titres (GMTs). Seropositive subjects were defined as subjects whose antibody titre was greater than or equal to (≥) the cut-off 8 serum dilution that induced 60 % inhibition in plaque forming units (ED60). | At Day 0 pre-vaccination | 
| Titres of RSV-A Neutralizing Antibodies | RSV-A neutralizing antibody titres, expressed as Geometric Mean Titres (GMTs). Seropositive subjects were defined as subjects whose antibody titre was greater than or equal to (≥) the cut-off 8 serum dilution that induced 60 % inhibition in plaque forming units (ED60). | At Day 30 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titres of RSV-A Neutralizing Antibodies | RSV-A neutralizing antibody titres, expressed as Geometric Mean Titres (GMTs), were defined as any titre greater than or equal to (≥) the cut-off 8 serum dilution inducing 60 % inhibition in plaque forming units (ED60). | At Day 60 post-vaccination | 
| Titres of RSV-A Neutralizing Antibodies | RSV-A neutralizing antibody titres, expressed as Geometric Mean Titres (GMTs), were defined as any titre greater than or equal to (≥) the cut-off 8 serum dilution inducing 60 % inhibition in plaque forming units (ED60). | At Day 90 post-vaccination | 
| Concentrations of Palivizumab Competing Antibodies (PCA) | Palivizumab competing antibody concentrations, expressed as Geometric Mean Concentrations (GMCs). The assay cut-off was greater than or equal to 3.34 micrograms per millilitre (µg/mL). | At Day 0 pre-vaccination | 
| Concentrations of PCA | PCA concentrations, expressed as Geometric Mean Concentrations (GMCs). The assay cut-off was greater than or equal to 3.34 micrograms per millilitre (µg/mL). | At Day 30 post-vaccination | 
| Concentrations of PCA | PCA concentrations, expressed as Geometric Mean Concentrations (GMCs).The assay cut-off was greater than or equal to 3.34 micrograms per millilitre (µg/mL). | At Day 60 post-vaccination | 
| Concentrations of PCA | PCA concentrations, expressed as Geometric Mean Concentrations (GMCs). The assay cut-off was greater than or equal to 3.34 micrograms per millilitre (µg/mL). | At Day 90 post-vaccination | 
| Number of Subjects With SAEs | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | Up to study end at Day 360 | 

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