Respiratory Syncytial Virus InfectionsPhase 2NCT02956837
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
A Phase 2 study testing RSV Vaccine (GSK3003891A) formulation 1, RSV Vaccine (GSK3003891A) formulation 2 and RSV Vaccine (GSK3003891A) formulation 3 in people with Respiratory Syncytial Virus Infections, run by GlaxoSmithKline at 8 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Respiratory Syncytial Virus Infections
- What is being tested?
- RSV Vaccine (GSK3003891A) formulation 1, RSV Vaccine (GSK3003891A) formulation 2 and RSV Vaccine (GSK3003891A) formulation 3
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 406 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 10 Nov 2016to 5 Feb 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
Germany3 sites
GSK Investigational Site
Goch, North Rhine-Westphalia, 47574
GSK Investigational Site
Hanover, Lower Saxony, 30159
GSK Investigational Site
Würzburg, Bavaria, 97070
Estonia2 sites
GSK Investigational Site
Tallinn, 10117
GSK Investigational Site
Tartu, 50106
France2 sites
GSK Investigational Site
Clermont-Ferrand, 63003
GSK Investigational Site
Paris, 75679
About this study
Official title: An Observer-blind Study to Rank Different Formulations of GSK Biologicals' Investigational RSV Vaccine (GSK3003891A) Administered to Healthy Women
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.
Read the 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.
- Conditions
- Respiratory Syncytial Virus Infections
- Being tested
- RSV Vaccine (GSK3003891A) formulation 1, RSV Vaccine (GSK3003891A) formulation 2, RSV Vaccine (GSK3003891A) formulation 3, Placebo (Formulation buffer S9b)
- Keywords
- Vaccines, Respiratory Syncytial Viruses, Safety, Reactogenicity, Ranking of Formulations, Immunogenicity
- Medical subject headings
- Respiratory Syncytial Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RSV Vaccine (GSK3003891A) formulation 1Biological
Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm.
RSV Vaccine (GSK3003891A) formulation 2Biological
Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm.
RSV Vaccine (GSK3003891A) formulation 3Biological
Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Biological: RSV Vaccine (GSK3003891A) formulation 3 |
| Control Group | Placebo comparator | Subjects in this group received a single placebo injection at Day 0. Receives: Drug: Placebo (Formulation buffer S9b) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: At Day 30
Secondary outcomes (14)
Number of Subjects With Any, Grade 2, Grade 3 and Medically Attended Solicited Local AEs
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 2 pain = painful when limb was moved and that interfered with every day activities.Grade 3 pain = significant pain at rest, pain that prevented normal every day activity. Grade 2 redness/swelling = redness/swelling spreading beyond (>) 50 millimeters (mm) and up to (and including) 100 mm of injection site.Grade 3 redness/swelling = redness/swelling > 100 mm of injection site. Medically attended symptoms = occurrence of symptoms that required medical advice.
Measured: 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
Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (which include nausea, vomiting, diarrhoea and/or abdominal pain), headache, fever [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 2 symptoms = occurrence of symptoms discomforting enough to interfere with daily activities. Grade 3 symptoms = symptoms that prevented normal activities.Related = symptom assessed by the investigator as related to the vaccination. Medically attended symptom = occurrence of symptom that required medical advice.
Measured: During the 7-day (Days 0-6) post-vaccination period
Number of Subjects With Any Unsolicited 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.
Measured: During the 30-day (Days 0-29) post-vaccination period
Number of Subjects With Any SAEs
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Measured: From Day 0 up to study end, at Day 360
Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
Biochemical parameters assessed included alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine. Hematological parameters assessed included eosinophils, hemoglobin level, lymphocytes, neutrophils, platelet count and White Blood Cells [WBC]. Abnormal laboratory values at Day 7 were Below, Within and Above normal ranges, as compared to the baseline status of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) [e.g. ALT Below - Within = ALT with below normal value at baseline and within normal values at Day 7].
Measured: At Day 7
Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
Biochemical parameters assessed included alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine. Hematological parameters assessed included eosinophils, hemoglobin level, lymphocytes, neutrophils, platelet count and White Blood Cells [WBC]. Abnormal laboratory values at Day 30 were Below, Within and Above normal ranges, as compared to the baseline values of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) [e.g. ALT Below - Within = ALT with below normal value at baseline and within normal values at Day 30].
Measured: At Day 30
Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
Biochemical parameters assessed included alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine. Hematological parameters assessed included eosinophils, hemoglobin level, lymphocytes, neutrophils, platelet count and White Blood Cells [WBC]. Abnormal laboratory values at Day 60 were Below, Within and Above normal ranges, as compared to the baseline status of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) [e.g. ALT Below - Within = ALT with below normal value at baseline and within normal values at Day 60].
Measured: At Day 60
Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
Biochemical parameters assessed included alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine. Hematological parameters assessed included eosinophils, hemoglobin level, lymphocytes, neutrophils, platelet count and White Blood Cells [WBC]. Abnormal laboratory values at Day 90 were Below, Within and Above normal ranges, as compared to the baseline status of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) [e.g. ALT Below - Within = ALT with below normal value at baseline and within normal values at Day 90].
Measured: At Day 90
Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities, by Maximum Grading
The biochemical and hematological parameters analyzed were ALT, AST, creatinine, eosinophils increase, hemoglobin decrease, lymphocytes decrease, neutrophils decrease, platelet count decrease, WBC decrease and WBC increase, which were graded by FDA Toxicity Grading Scale. Assessed grades over the Day 7- Day 90 period were Unknown, Grade 0 (=no grade), Grade 1 (=mild), Grade 2 (=moderate), Grade 3 (=severe) and Grade 4 (=potentially life-threatening), as compared to the baseline status of the same parameters, at Day 0 (Unknown, Grade 1, Grade 2, Grade 3) [e.g. ALT Grade 0 - Unknown = ALT Grade 0 at baseline versus Unknown grade from Day 7 up to Day 90].
Measured: From Day 7 up to Day 90
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.
Measured: At Day 60 and Day 90
Neutralizing Antibody Titers Against RSV-B Subtype
RSV-B 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 ≥ 6 ED60.
Measured: At Day 0, Day 30, Day 60 and Day 90
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 value ≥ 9.6 µg/mL.
Measured: At Day 60 and Day 90
Antibody Concentrations Against Neogenin (NEO) Residual Host Cell Protein
Anti-neogenin (anti-NEO) antibody concentrations were determined by ELISA, presented as geometric mean concentrations (GMCs) and expressed in nanograms per milliliter (ng/mL), for a seropositivity cut-off value ≥ 55 ng/mL.
Measured: At Day 0 and Day 30
Number of Subjects With Any Medically Attended (MA) Respiratory Tract Infections (RTIs) Associated With RSV
MA-RSV-RTIs were defined as a visit to a health care provider for respiratory symptoms including but not limited to cough, sputum production, difficulty breathing.
Measured: From Day 0 up to study end, at Day 360
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2016 (estimated)
- Study start10 Nov 2016
- Primary completion30 Aug 2017
- Study completion5 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Respiratory Syncytial Virus InfectionsStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 406 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02956837
- Sponsor's protocol ID
- 204812
- Other IDs
- 2016-001135-12, 2016
- Status last verified
- Jun 2019
- First submitted
- 3 Nov 2016
- Last updated
- 2 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
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.
PubMed 31951765Schwarz 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.
PubMed 31418022
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observer-blind Study to Rank Different Formulations of GSK Biologicals' Investigational RSV Vaccine (GSK3003891A) Administered to Healthy Women
- ClinicalTrials.gov ID
- NCT02956837
- Acronym / sponsor ID
- 204812
- Conditions
- Respiratory Syncytial Virus Infections
- Keywords
- Vaccines, Respiratory Syncytial Viruses, Safety, Reactogenicity, Ranking of Formulations, Immunogenicity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 406 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 10 Nov 2016 (actual)
- Primary completion
- 30 Aug 2017 (actual)
- Study completion
- 5 Feb 2018 (actual)
- First posted
- 7 Nov 2016 (estimated)
- Results
- Posted 20 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GSK3003891A vaccine formulation 1 Group | Experimental | Biological: RSV Vaccine (GSK3003891A) formulation 1Subjects in this group received a single 30 micrograms (µg) dose injection of the investigational GSK3003891A vaccine at Day 0. |
| GSK3003891A vaccine formulation 2 Group | Experimental | Biological: RSV Vaccine (GSK3003891A) formulation 2Subjects in this group received a single 60µg dose injection of the investigational GSK3003891A vaccine at Day 0. |
| GSK3003891A vaccine formulation 3 Group | Experimental | Biological: RSV Vaccine (GSK3003891A) formulation 3Subjects in this group received a single 120µg dose injection of the investigational GSK3003891A vaccine at Day 0. |
| Control Group | Placebo comparator | Drug: Placebo (Formulation buffer S9b)Subjects in this group received a single placebo injection at Day 0. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RSV Vaccine (GSK3003891A) formulation 1Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm. | Biological | GSK3003891A vaccine formulation 1 Group |
| RSV Vaccine (GSK3003891A) formulation 2Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm. | Biological | GSK3003891A vaccine formulation 2 Group |
| RSV Vaccine (GSK3003891A) formulation 3Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm. | Biological | GSK3003891A vaccine formulation 3 Group |
| Placebo (Formulation buffer S9b)A single dose of placebo is administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm. | Drug | Control Group |
Primary outcome
Number of Subjects With Any Grade 2 and Grade 3 General Adverse Events (AEs) - Solicited and Unsolicited
Time frame: During the 7-day (Days 0-6) post-vaccination period
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).
Number of Subjects With Grade 2 and Grade 3 Fever
Time frame: During the 7-day (Days 0-6) post-vaccination period
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).
Number of Subjects With Related Serious Adverse Events (SAEs)
Time frame: During the 7-day (Days 0-6) post-vaccination period
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).
Neutralizing Antibody Titers Against RSV-A Subtype
Time frame: At Day 0
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).
Neutralizing Antibody Titers Against RSV-A Subtype
Time frame: At Day 30
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).
Palivizumab Competing Antibody (PCA) Concentrations
Time frame: At Day 0
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).
Pavilizumab Competing Antibody (PCA) Concentrations
Time frame: At Day 30
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).
14 secondary outcomes
Number of Subjects With Any, Grade 2, Grade 3 and Medically Attended Solicited Local AEs
Time frame: 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
Time frame: During the 7-day (Days 0-6) post-vaccination period
Number of Subjects With Any Unsolicited AEs
Time frame: During the 30-day (Days 0-29) post-vaccination period
Number of Subjects With Any SAEs
Time frame: From Day 0 up to study end, at Day 360
Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
Time frame: At Day 7
Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
Time frame: At Day 30
Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
Time frame: At Day 60
Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities
Time frame: At Day 90
Number of Subjects With Any Biochemical and Hematological Laboratory Abnormalities, by Maximum Grading
Time frame: From Day 7 up to Day 90
Neutralizing Antibody Titers Against RSV-A Subtype
Time frame: At Day 60 and Day 90
Neutralizing Antibody Titers Against RSV-B Subtype
Time frame: At Day 0, Day 30, Day 60 and Day 90
Palivizumab Competing Antibody (PCA) Concentrations
Time frame: At Day 60 and Day 90
Antibody Concentrations Against Neogenin (NEO) Residual Host Cell Protein
Time frame: At Day 0 and Day 30
Number of Subjects With Any Medically Attended (MA) Respiratory Tract Infections (RTIs) Associated With RSV
Time frame: From Day 0 up to study end, at Day 360
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31951765Steff 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.
- Derived from this study: PubMed 31418022Schwarz 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.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RSV Vaccine (GSK3003891A) formulation 1, RSV Vaccine (GSK3003891A) formulation 2 and RSV Vaccine (GSK3003891A) formulation 3 in people with Respiratory Syncytial Virus Infections, run by GlaxoSmithKline at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany, Estonia, France, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Any Grade 2 and Grade 3 General Adverse Events (AEs) - Solicited and Unsolicited (time frame: During the 7-day (Days 0-6) post-vaccination period). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02956837, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2019.