A Study to Rank Different Dosages of Antigen of GlaxoSmithKline (GSK) Biologicals' Investigational Respiratory Syncytial Virus (RSV) Vaccine (GSK3003891A), Based on Their Immune Response and Safety, When Administered to Healthy Adult Women

NCT02956837 | Completed Phase 2 Results

• 2 other identifiers: 2048122016-001135-12
• Study Type: interventional
• Target: 406
• Locations: 4 countries
• Sites: 8

Brief Summary

The purpose of this study is to rank different RSV vaccine dosages of antigen (or formulations) based on safety/reactogenicity and immune response data. The formulations eliciting strong immune responses while maintaining an acceptable safety profile will be considered for further evaluation, including in studies vaccinating pregnant women.

Conditions

Respiratory Syncytial Virus Infections

Keywords

Vaccines; Respiratory Syncytial Viruses; Safety; Reactogenicity; Ranking of Formulations; Immunogenicity

Outcome Measures

Primary Outcomes (7)

• Number of Subjects With Any Grade 2 and Grade 3 General Adverse Events (AEs) - Solicited and Unsolicited

  Assessed solicited general AEs were fatigue, gastrointestinal symptoms \[nausea, vomiting, diarrhea and/or abdominal pain\], fever and headache. 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.Grade 2 symptoms = occurrence of symptoms discomforting enough to interfere with daily activities. Grade 3 symptoms = symptoms that prevented normal activities. This primary objective focused only on subjects from the investigational GSK3003891A vaccine groups (GSK3003891A vaccine formulation 1 Group, GSK3003891A vaccine formulation 2 Group and GSK3003891A vaccine formulation 3 Group).

  During the 7-day (Days 0-6) post-vaccination period

• Number of Subjects With Grade 2 and Grade 3 Fever

  Grade 2 Fever was defined as oral temperature above (\>) 38.5 degrees Celsius (°C) to less than or equal to (≤) 39.5°C. Grade 3 Fever was defined as oral temperature \> 39.5°C. This primary objective focused only on subjects from the investigational GSK3003891A vaccine groups (GSK3003891A vaccine formulation 1 Group, GSK3003891A vaccine formulation 2 Group and GSK3003891A vaccine formulation 3 Group).

  During the 7-day (Days 0-6) post-vaccination period

• Number of Subjects With Related Serious Adverse Events (SAEs)

  SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Related SAEs = SAEs assessed by the investigator as related to the vaccination. This primary objective focused only on subjects from the investigational GSK3003891A vaccine groups (GSK3003891A vaccine formulation 1 Group, GSK3003891A vaccine formulation 2 Group and GSK3003891A vaccine formulation 3 Group).

  During the 7-day (Days 0-6) post-vaccination period

• Neutralizing Antibody Titers Against RSV-A Subtype

  RSV-A is one of the two antigenically distinct subgroups of the Respiratory Synctial Virus (RSV). Antibody titers were determined by neutralization assay and presented as geometric mean titers (GMTs), for a seropositivity cut-off value greater than or equal to (≥) 8 ED60 (Estimated Dilution 60). This primary objective focused only on subjects from the investigational GSK3003891A vaccine groups (GSK3003891A vaccine formulation 1 Group, GSK3003891A vaccine formulation 2 Group and GSK3003891A vaccine formulation 3 Group).

  At Day 0

• Neutralizing Antibody Titers Against RSV-A Subtype

  RSV-A is one of the two antigenically distinct subgroups of the Respiratory Synctial Virus (RSV). Antibody titers were determined by neutralization assay and presented as geometric mean titers (GMTs), for a seropositivity cut-off value ≥ 8 ED60 (Estimated Dilution 60). This primary objective focused only on subjects from the investigational GSK3003891A vaccine groups (GSK3003891A vaccine formulation 1 Group, GSK3003891A vaccine formulation 2 Group and GSK3003891A vaccine formulation 3 Group).

  At Day 30

• Palivizumab Competing Antibody (PCA) Concentrations

  PCA concentrations were determined by Enzyme-Linked Immunosorbent Assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL), for a seropositivity cut-off ≥ 9.6 µg/mL. This primary objective focused only on subjects from the investigational GSK3003891A vaccine groups (GSK3003891A vaccine formulation 1 Group, GSK3003891A vaccine formulation 2 Group and GSK3003891A vaccine formulation 3 Group).

  At Day 0

• Pavilizumab Competing Antibody (PCA) Concentrations

  PCA concentrations were determined by Enzyme-Linked Immunosorbent Assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL), for a seropositivity cut-off ≥ 9.6 µg/mL. This primary objective focused only on subjects from the investigational GSK3003891A vaccine groups (GSK3003891A vaccine formulation 1 Group, GSK3003891A vaccine formulation 2 Group and GSK3003891A vaccine formulation 3 Group).

  At Day 30

Secondary Outcomes (14)

• Number of Subjects With Any, Grade 2, Grade 3 and Medically Attended Solicited Local AEs

  During the 7-day (Days 0-6) post-vaccination period

• Number of Subjects With Any, Grade 2, Grade 3, Related and Medically Attended Solicited General AEs

  During the 7-day (Days 0-6) post-vaccination period

• Number of Subjects With Any Unsolicited AEs

  During the 30-day (Days 0-29) post-vaccination period

• Number of Subjects With Any SAEs

  From Day 0 up to study end, at Day 360

• Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities

  At Day 7

Study Arms (4)

GSK3003891A vaccine formulation 1 Group

EXPERIMENTAL

Subjects in this group received a single 30 micrograms (µg) dose injection of the investigational GSK3003891A vaccine at Day 0.

Biological: RSV Vaccine (GSK3003891A) formulation 1

GSK3003891A vaccine formulation 2 Group

EXPERIMENTAL

Subjects in this group received a single 60µg dose injection of the investigational GSK3003891A vaccine at Day 0.

Biological: RSV Vaccine (GSK3003891A) formulation 2

GSK3003891A vaccine formulation 3 Group

EXPERIMENTAL

Subjects in this group received a single 120µg dose injection of the investigational GSK3003891A vaccine at Day 0.

Biological: RSV Vaccine (GSK3003891A) formulation 3

Control Group

PLACEBO COMPARATOR

Subjects in this group received a single placebo injection at Day 0.

Drug: Placebo (Formulation buffer S9b)

Interventions

RSV Vaccine (GSK3003891A) formulation 1 BIOLOGICAL

Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm.

GSK3003891A vaccine formulation 1 Group

RSV Vaccine (GSK3003891A) formulation 2 BIOLOGICAL

Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm.

GSK3003891A vaccine formulation 2 Group

RSV Vaccine (GSK3003891A) formulation 3 BIOLOGICAL

Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm.

GSK3003891A vaccine formulation 3 Group

Placebo (Formulation buffer S9b) DRUG

A single dose of placebo is administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm.

Control Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 performance of 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
• Non-childbearing potential is defined as pre-menarche, hysterectomy, ovariectomy or post-menopause.
• 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 up to 90 days after vaccination.

You may not qualify if:

• Use of any investigational or non-registered product other than the study vaccines within 30 days prior to study vaccination, or planned use during the study period.
• Concurrently participating in the active phase of 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.
• Chronic administration of immunosuppressants or other immune-modifying drugs, as well as administration of long-acting immune-modifying drugs, within 6 months prior to study vaccination, or planned administration until 90 days post-vaccination. For corticosteroids, this will mean prednisone ≥ 10 mg/day, or equivalent. Inhaled and topical steroids are allowed.
• Administration of immunoglobulins and/or any blood products during the period starting 3 months before the study vaccination, or planned administration until 90 days post-vaccination.
• 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 neurological disorders or seizures.
• Family history of congenital or hereditary immunodeficiency.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
• History of or current autoimmune disease
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality as determined by physical examination and/or Medical History.
• Lymphoproliferative disorder or malignancy within previous 5 years.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine.
• Hypersensitivity to latex.
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (8)

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Tallinn, 10117, Estonia

Location

GSK Investigational Site

Tartu, 50106, Estonia

Location

GSK Investigational Site

Clermont-Ferrand, 63003, France

Location

GSK Investigational Site

Paris, 75679, France

Location

GSK Investigational Site

Würzburg, Bavaria, 97070, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30159, Germany

Location

GSK Investigational Site

Goch, North Rhine-Westphalia, 47574, Germany

Location

Related Publications (2)

• 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.

  PMID: 31951765 DERIVED

• Schwarz TF, McPhee RA, Launay O, Leroux-Roels G, Talli J, Picciolato M, Gao F, Cai R, Nguyen TL, Dieussaert I, Miller JM, Schmidt AC. Immunogenicity and Safety of 3 Formulations of a Respiratory Syncytial Virus Candidate Vaccine in Nonpregnant Women: A Phase 2, Randomized Trial. J Infect Dis. 2019 Oct 22;220(11):1816-1825. doi: 10.1093/infdis/jiz395.

  PMID: 31418022 DERIVED

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Interventions

Respiratory Syncytial Virus Vaccines

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

shm60684@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2016
• First Posted: November 7, 2016
• Study Start: November 10, 2016
• Primary Completion: August 30, 2017
• Study Completion: February 5, 2018
• Last Updated: July 2, 2019
• Results First Posted: November 20, 2018

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• 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.

Locations

BE (1); FR (2); ES (2); DE (3)