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

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infections
• Intervention / Treatment: Biological: RSV vaccine GSK3003895A (formulation 1); Biological: RSV vaccine GSK3003898A (formulation 2); Biological: RSV vaccine GSK3003899A (formulation 3); Biological: Boostrix

• Study Type: Interventional
• Enrollment (Actual): 507
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • GSK Investigational Site
• Czechia
  • Hradec Kralove, Czechia
    • GSK Investigational Site
• Germany
  • Bayern
    • Wuerzburg, Bayern, Germany, 97070
      • GSK Investigational Site
  • Sachsen
    • Dippoldiswalde, Sachsen, Germany, 01744
      • GSK Investigational Site
  • Schleswig-Holstein
    • Luebeck, Schleswig-Holstein, Germany, 23554
      • GSK Investigational Site
• United States
  • Arizona
    • Mesa, Arizona, United States, 85213
      • GSK Investigational Site
  • California
    • San Diego, California, United States, 92108
      • GSK Investigational Site
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • GSK Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • GSK Investigational Site
  • Massachusetts
    • Milford, Massachusetts, United States, 01757
      • GSK Investigational Site
  • New York
    • Syracuse, New York, United States, 13210
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78705
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: RSV vaccine formulation 1 Group; Subjects in this group will receive a single dose of formulation 1 of the RSV vaccine	Biological: RSV vaccine GSK3003895A (formulation 1); Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm
EXPERIMENTAL: RSV vaccine formulation 2 Group; Subjects in this group will receive a single dose of formulation 2 of RSV vaccine	Biological: RSV vaccine GSK3003898A (formulation 2); Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm
EXPERIMENTAL: RSV vaccine formulation 3 Group; Subjects in this group will receive a single dose of formulation 3 of RSV vaccine	Biological: RSV vaccine GSK3003899A (formulation 3); Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm
ACTIVE_COMPARATOR: Boostrix Group; Subjects in this group will receive a single dose of Boostrix	Biological: Boostrix; Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Beran J, Lickliter JD, Schwarz TF, Johnson C, Chu L, Domachowske JB, Van Damme P, Withanage K, Fissette LA, David MP, Maleux K, Schmidt AC, Picciolato M, Dieussaert I. Safety and Immunogenicity of 3 Formulations of an Investigational Respiratory Syncytial Virus Vaccine in Nonpregnant Women: Results From 2 Phase 2 Trials. J Infect Dis. 2018 Apr 23;217(10):1616-1625. doi: 10.1093/infdis/jiy065.
• Steff AM, Cadieux-Dion C, de Lannoy G, Prato MK, Czeszak X, Andre B, Ingels DC, Louckx M, Dewe W, Picciolato M, Maleux K, Fissette L, Dieussaert I. Hamster neogenin, a host-cell protein contained in a respiratory syncytial virus candidate vaccine, induces antibody responses in rabbits but not in clinical trial participants. Hum Vaccin Immunother. 2020 Jun 2;16(6):1327-1337. doi: 10.1080/21645515.2019.1693749. Epub 2020 Jan 17.

Helpful Links

• IPD for this study will be made available via the Clinical Study Data Request site.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 20, 2015
• Primary Completion (ACTUAL): July 2, 2015
• Study Completion (ACTUAL): June 21, 2016

Study Registration Dates

• First Submitted: January 29, 2015
• First Submitted That Met QC Criteria: February 5, 2015
• First Posted (ESTIMATE): February 10, 2015

Study Record Updates

• Last Update Posted (ACTUAL): July 3, 2018
• Last Update Submitted That Met QC Criteria: May 31, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Safety; Vaccine; Immunogenicity; Reactogenicity; Respiratory syncytial virus (RSV)
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Respiratory Syncytial Virus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 201510; 2014-002688-14 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR