Clinical trial NCT02956837: 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
Official title: An Observer-blind Study to Rank Different Formulations of GSK Biologicals' Investigational RSV Vaccine (GSK3003891A) Administered to Healthy Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infections
Keywords: Vaccines
Respiratory Syncytial Viruses
Safety
Reactogenicity
Ranking of Formulations
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-11-06
Enrollment: 406
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: The purpose of the RSV F-021 study that will be conducted in an observer-blind manner during Epoch 1 and single blinded during Epoch 2, is to rank the 3 different doses of the non-adjuvanted investigational RSV PreF-vaccine (30, 60 and 120 μg) based on safety/reactogenicity and immunogenicity data up to 1 month post-vaccination (Day 30). Non-pregnant women aged 18-45 years will be randomized in a 1:1:1:1 ratio to receive one of three dose levels (30, 60, 120 μg) of the RSV PreF vaccine or placebo. The doses eliciting strong immune responses while maintaining an acceptable safety profile will be considered for further evaluation, including in studies vaccinating pregnant women. This will allow evaluation of a wider antigen dose range to determine if there is a dose response relationship in terms of antibody response at the higher dose range that was not present at the lower range.

Since in RSV F-021 the 120ug dosage of the PreF-based investigational RSV vaccine will be tested for the first time in humans, appropriate safety monitoring is planned for this study, including pausing enrolment when the first 25% of subjects from each study group have been vaccinated until review of day 7 post-vaccination safety data by an unblinded GSK internal Safety Review Committee (iSRC) has been completed. The enrolment/vaccination of the remaining subjects can only start following the favourable outcome of this iSRC safety review.

In addition to study visits at Day 0, Day 7 and Day 30 to evaluate primary objective of the study, additional study visits are planned at Day 60 and 90 for further investigation of the immunogenicity and safety/reactogenicity profile of the formulations. A follow-up period has been set up in which the subjects will be contacted at Day 180, 270 and 360. During these contacts, the investigator (or delegate) will ask the subject if she has experienced any serious adverse events and/or any AEs leading to study withdrawal since Day 90/last contact (as applicable), as well as if she has become pregnant during the post-vaccination period. The investigator (or delegate) will also ask the subject about concomitant vaccinations/products/medications that she has received since Day 90/last contact (as applicable) and whether the she had a respiratory tract infection that needed medical attention. Contact should be preferably performed via telephone, or alternatively, if phone contact is not possible, through email/other means where the information can be fully collected.

Healthy, non-pregnant women aged 18 - 45 years will be enrolled in this study:

Women aged 18 - 45 years are selected to match the vaccine's target population, i.e. pregnant women, as closely as possible (gender, age).

Non-pregnant women are selected to avoid unnecessarily exposing a vulnerable population (pregnant women and the foetuses/children) to a higher dose of the vaccine that has not previously been studied in non-pregnant women.

Eligibility criteria: 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 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.

Exclusion Criteria:

* 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.
* Current alcohol and/or drug abuse.
* Acute disease and/or fever at the time of enrolment.

  * Fever is defined as temperature ≥37.5°C for oral, axillary or tympanic route, or ≥ 38.0°C for rectal route.
  * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
  * For subjects with acute disease and/or fever at the time of enrolment, Visit 1/Day 0 will be rescheduled within the allowed recruitment period.
* Body mass index (BMI) \> 40 kg/m².
* Pregnant or lactating female.
* Planned move to a location that will prohibit participating in the trial until study conclusion.
* Any other condition that the investigator judges may interfere with study procedures or findings.

Primary outcomes:
measure: Number of Subjects With Any Grade 2 and Grade 3 General Adverse Events (AEs) - Solicited and Unsolicited
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects With Grade 2 and Grade 3 Fever
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects With Related Serious Adverse Events (SAEs)
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Neutralizing Antibody Titers Against RSV-A Subtype
timeFrame: At Day 0
measure: Neutralizing Antibody Titers Against RSV-A Subtype
timeFrame: At Day 30
measure: Palivizumab Competing Antibody (PCA) Concentrations
timeFrame: At Day 0
measure: Pavilizumab Competing Antibody (PCA) Concentrations
timeFrame: At Day 30
Secondary outcomes:
measure: Number of Subjects With Any, Grade 2, Grade 3 and Medically Attended Solicited Local AEs
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects With Any, Grade 2, Grade 3, Related and Medically Attended Solicited General AEs
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects With Any Unsolicited AEs
timeFrame: During the 30-day (Days 0-29) post-vaccination period
measure: Number of Subjects With Any SAEs
timeFrame: From Day 0 up to study end, at Day 360
measure: Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
timeFrame: At Day 7
measure: Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
timeFrame: At Day 30
measure: Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
timeFrame: At Day 60
measure: Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
timeFrame: At Day 90
measure: Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities, by Maximum Grading
timeFrame: From Day 7 up to Day 90
measure: Neutralizing Antibody Titers Against RSV-A Subtype
timeFrame: At Day 60 and Day 90
measure: Neutralizing Antibody Titers Against RSV-B Subtype
timeFrame: At Day 0, Day 30, Day 60 and Day 90
measure: Palivizumab Competing Antibody (PCA) Concentrations
timeFrame: At Day 60 and Day 90
measure: Antibody Concentrations Against Neogenin (NEO) Residual Host Cell Protein
timeFrame: At Day 0 and Day 30
measure: Number of Subjects With Any Medically Attended (MA) Respiratory Tract Infections (RTIs) Associated With RSV
timeFrame: From Day 0 up to study end, at Day 360
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Clermont-Ferrand
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Goch
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.