Respiratory Syncytial Virus Infections
Conditions
Keywords
Respiratory syncytial virus, Vaccine, Safety, Immunogenicity
Brief summary
Nine different formulations of the RSVPreF3 OA investigational vaccine were tested in the parent study (NCT03814590). Based on safety and immunogenicity data from the parent study, RSVPreF3 OA investigational vaccine will be evaluated in further clinical research. Participants in selected groups will be invited to participate in this extension study. All participants who will be enrolled in the current extension study will receive the RSV investigational vaccine approximately 18 months after they received their respective dose-2 in the parent study.
Interventions
BIOLOGICALRSVPreF3 OA investigational vaccine (GSK3844766A)
RSVPreF3 OA investigational vaccine administered intramuscularly in the deltoid region of the non-dominant arm, at Day 1 (18 months post-Dose 2 in the RSV OA=ADJ-002 parent study).
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
This is an open-label study, as all participants will receive the same RSVPreF3 OA investigational vaccine. No blind is used. Both the investigator and the participant know the identity of the intervention assigned.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female participants, who received 2 doses of RSVPreF3 OA investigational vaccine and formulations with matched adjuvant in part B of the parent study RSV OA=ADJ-002: recombinant RSVPreF3 antigen doses of low, medium and high strengths with adjuvant. * Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for the follow-up visit, be available for contact) * Written informed consent obtained from the participant prior to performance of any study specific procedure.
Exclusion criteria
Medical conditions * Significant underlying illness or administered therapy that in the opinion of the investigator would be expected to prevent participation in the study. * Any confirmed or suspected immunosuppressive or immunodeficient condition based on information on concomitant medication/vaccination collected prior to the study start and physical examination. * Serious or unstable chronic illness that developed during or after the parent study. Patients with chronic stable medical conditions with or without specific treatment, such as diabetes, hypertension or cardiac disease, are allowed to participate in this study if considered by the investigator as clinically stable. * Recurrent or un-controlled neurological disorders or seizures that developed during or after the parent study. Participants with medically-controlled active or chronic neurological diseases can be enrolled in the study as per investigator assessment, provided that their condition will allow them to comply with the requirements of the protocol. * Significant underlying illness that developed during or after the parent study, that in the opinion of the investigator would be expected to prevent completion of the study. * Lymphoproliferative disorder and malignancy developed during or after the parent study. * Any medical condition that developed during or after the parent study, that in the judgment of the investigator would make intramuscular injection unsafe. * Previous vaccination with RSV vaccine, other than the one in the parent study. Prior/Concomitant therapy * Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccine during the period beginning 30 days before the dose of study vaccine, or planned use during the study period. * Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after the dose of study vaccine administration, with the exception of inactivated, split virion and subunit influenza vaccines which can be administered up to 14 days before or from 30 days after the study vaccination. * Administration of long-acting immune-modifying drugs or planned administration at any time during the study period. * Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the dose of study vaccine or planned administration during the study period. * Chronic administration (defined as more than 14 consecutive days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the vaccine dose or planned administration during the study period. For corticosteroids, this will mean prednisone ≥20 mg/day, or equivalent. Inhaled and topical steroids are allowed. * Confirmed use or anticipated use of immunosuppressive/cytotoxic therapy. Prior/Concurrent clinical study experience • Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product. Other exclusions * Bedridden participants. * Planned move to a location that will prohibit participating in the trial. * History of chronic alcohol consumption and/or drug abuse that developed during or after the parent study as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Humoral Immune Response in Terms of Neutralizing Antibody Titers Against RSV-serotype B | At 30 days post-vaccination (Day 31) | Serological assays for the determination of functional antibodies against RSV-B are performed by neutralization assay. Anti RSV-B neutralizing antibody titers are given as GMTs and expressed as ED60. |
| Number of Participants With Any Unsolicited AEs | During the 30-day follow-up period post-vaccination (i.e., on the day of vaccination [Day 1] and 29 subsequent days) | An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to study vaccination. |
| Number of Participants With Any Serious Adverse Events (SAEs) up to 30 Days Post-vaccination | From Day 1 up to 30 days post-vaccination (Day 31) | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. Any is defined as any occurrence of SAE regardless of intensity grade or relation to study vaccination. |
| Number of Participants With Any Potential Immune-mediated Diseases (pIMDs) up to 30 Days Post-vaccination | From Day 1 up to 30 days post-vaccination (Day 31) | pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. Any is defined as the occurrence of any pIMD regardless of intensity grade or relation to study vaccination. |
| Humoral Immune Response in Terms of Neutralizing Antibody Titers Against Respiratory Syncytial Virus (RSV)-Serotype A | At 30 days post-vaccination (Day 31) | Serological assays for the determination of functional antibodies against RSV-A are performed by neutralization assay. Anti RSV-A neutralizing antibody titers are given as Geometric Mean Titers (GMTs) and expressed as Estimated Dose: serum dilution giving a 60% reduction of the signal compared to a control without serum (ED60). |
| Number of Participants With Any Solicited Administration Site Adverse Events (AEs) | During the 4-day follow-up period post-vaccination (i.e. on the day of vaccination [Day 1] and 3 subsequent days) | Assessed solicited administration site AEs are erythema, pain and swelling. Any pain is defined as any pain regardless of intensity grade. Any injection site erythema/swelling is scored with a diameter larger than (\>) 20 millimeters (mm). |
| Number of Participants With Any Solicited Systemic AEs | During the 4-day follow-up period post-vaccination (i.e. on the day of vaccination [Day 1] and 3 subsequent days) | Assessed solicited systemic AE is fever (any temperature greater than or equal to 38.0 °C - the preferred location for measuring temperature being the oral cavity). Any is defined as occurrence of the symptom regardless of intensity grade or relation to study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of RSVPreF3-specific Cluster of Differentiation 4+ (CD4+) T-cells Identified as Expressing at Least Two Markers | At 30 days post-vaccination (Day 31) | Among markers expressed are interleukin-2 (IL2), cluster of 40 ligand (CD40L), tumour necrosis factor alpha (TNF α) and interferon gamma (IFN γ), in vitro upon stimulation with RSVPreF3 peptide preparations. |
| Number of Participants With Any SAEs, up the End of Follow-up Study Period (Month 6) | From Day 1 up to the end of follow-up period (Month 6) | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. |
| Number of Participants Reporting pIMDs up to the End of Follow-up Study Period (Month 6) | From Day 1 up to the end of follow-up period (Month 6) | pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. |
| Humoral Immune Response in Terms of RSVPreF3-specific Immunoglobulin G (IgG) Antibody Concentrations | At 30 days post-vaccination (Day 31) | The detection and the quantification of total IgG antibodies directed against RSVPreF3 in human serum samples were based on an indirect Enzyme-Linked Immunosorbent Assay (ELISA). Anti RSVPreF3 antibody concentration is given in geometric mean concentration (GMC) and is expressed in ELISA Laboratory Units per milliliter (ELU/mL). |
Countries
Belgium, United States
Participant flow
Recruitment details
From a total of 126 participants enrolled in this study, 4 participants were withdrawn before vaccination. 122 participants received the study vaccination.
Participants by arm
| Arm | Count |
|---|---|
| High Dose_AS01E Group Participants received 1 dose of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E in the current study after having received 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E in the RSV OA=ADJ-002 (NCT03814590) parent study. | 40 |
| Low Dose_AS01E Group Participants received 1 dose of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E in the current study after having received 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E in the RSV OA=ADJ-002 (NCT03814590) parent study. | 39 |
| Medium Dose_AS01E Group Participants received 1 dose of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E in the current study after having received 2 doses of the RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01E in the RSV OA=ADJ-002 (NCT03814590) parent study. | 43 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | CONSENT WITHDRAWAL, NOT DUE TO A (S)AE | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | High Dose_AS01E Group | Low Dose_AS01E Group | Medium Dose_AS01E Group | Total |
|---|---|---|---|---|
| Age, Continuous | 68.3 Years STANDARD_DEVIATION 5.4 | 69.1 Years STANDARD_DEVIATION 5.3 | 66.6 Years STANDARD_DEVIATION 5.6 | 68.0 Years STANDARD_DEVIATION 5.5 |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black Or African American | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 38 Participants | 37 Participants | 42 Participants | 117 Participants |
| Sex: Female, Male Female | 27 Participants | 21 Participants | 24 Participants | 72 Participants |
| Sex: Female, Male Male | 13 Participants | 18 Participants | 19 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 39 | 0 / 43 |
| other Total, other adverse events | 22 / 40 | 25 / 39 | 29 / 43 |
| serious Total, serious adverse events | 1 / 40 | 1 / 39 | 2 / 43 |
Outcome results
Primary
Humoral Immune Response in Terms of Neutralizing Antibody Titers Against Respiratory Syncytial Virus (RSV)-Serotype A
Serological assays for the determination of functional antibodies against RSV-A are performed by neutralization assay. Anti RSV-A neutralizing antibody titers are given as Geometric Mean Titers (GMTs) and expressed as Estimated Dose: serum dilution giving a 60% reduction of the signal compared to a control without serum (ED60).
Time frame: At 30 days post-vaccination (Day 31)
Population: The analysis was performed on the Per Protocol Set (that included participants who received the study intervention dose and have post-vaccination data, minus participants with protocol deviations that led to exclusion), for the High Dose\_AS01E Group only (as per protocol).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| High Dose_AS01E Group | Humoral Immune Response in Terms of Neutralizing Antibody Titers Against Respiratory Syncytial Virus (RSV)-Serotype A | 4394.9 Titers |
Primary
Humoral Immune Response in Terms of Neutralizing Antibody Titers Against RSV-serotype B
Serological assays for the determination of functional antibodies against RSV-B are performed by neutralization assay. Anti RSV-B neutralizing antibody titers are given as GMTs and expressed as ED60.
Time frame: At 30 days post-vaccination (Day 31)
Population: The analysis was performed on the Per Protocol Set (that included participants who received the study intervention dose and have post-vaccination data, minus participants with protocol deviations that led to exclusion), for the High Dose\_AS01E Group only (as per protocol).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| High Dose_AS01E Group | Humoral Immune Response in Terms of Neutralizing Antibody Titers Against RSV-serotype B | 6094.3 Titers |
Primary
Number of Participants With Any Potential Immune-mediated Diseases (pIMDs) up to 30 Days Post-vaccination
pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. Any is defined as the occurrence of any pIMD regardless of intensity grade or relation to study vaccination.
Time frame: From Day 1 up to 30 days post-vaccination (Day 31)
Population: The analysis was performed on the Exposed Set that included all participants who received the study intervention dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose_AS01E Group | Number of Participants With Any Potential Immune-mediated Diseases (pIMDs) up to 30 Days Post-vaccination | 0 Participants |
| Low Dose_AS01E Group | Number of Participants With Any Potential Immune-mediated Diseases (pIMDs) up to 30 Days Post-vaccination | 0 Participants |
| Medium Dose_AS01E Group | Number of Participants With Any Potential Immune-mediated Diseases (pIMDs) up to 30 Days Post-vaccination | 0 Participants |
Primary
Number of Participants With Any Serious Adverse Events (SAEs) up to 30 Days Post-vaccination
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. Any is defined as any occurrence of SAE regardless of intensity grade or relation to study vaccination.
Time frame: From Day 1 up to 30 days post-vaccination (Day 31)
Population: The analysis was performed on the Exposed Set that included all participants who received the study intervention dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose_AS01E Group | Number of Participants With Any Serious Adverse Events (SAEs) up to 30 Days Post-vaccination | 0 Participants |
| Low Dose_AS01E Group | Number of Participants With Any Serious Adverse Events (SAEs) up to 30 Days Post-vaccination | 0 Participants |
| Medium Dose_AS01E Group | Number of Participants With Any Serious Adverse Events (SAEs) up to 30 Days Post-vaccination | 0 Participants |
Primary
Number of Participants With Any Solicited Administration Site Adverse Events (AEs)
Assessed solicited administration site AEs are erythema, pain and swelling. Any pain is defined as any pain regardless of intensity grade. Any injection site erythema/swelling is scored with a diameter larger than (\>) 20 millimeters (mm).
Time frame: During the 4-day follow-up period post-vaccination (i.e. on the day of vaccination [Day 1] and 3 subsequent days)
Population: The analysis was performed on the Exposed Set that included all participants who received the study intervention dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose_AS01E Group | Number of Participants With Any Solicited Administration Site Adverse Events (AEs) | Any pain | 21 Participants |
| High Dose_AS01E Group | Number of Participants With Any Solicited Administration Site Adverse Events (AEs) | Any erythema | 1 Participants |
| High Dose_AS01E Group | Number of Participants With Any Solicited Administration Site Adverse Events (AEs) | Any swelling | 0 Participants |
| Low Dose_AS01E Group | Number of Participants With Any Solicited Administration Site Adverse Events (AEs) | Any pain | 23 Participants |
| Low Dose_AS01E Group | Number of Participants With Any Solicited Administration Site Adverse Events (AEs) | Any erythema | 6 Participants |
| Low Dose_AS01E Group | Number of Participants With Any Solicited Administration Site Adverse Events (AEs) | Any swelling | 2 Participants |
| Medium Dose_AS01E Group | Number of Participants With Any Solicited Administration Site Adverse Events (AEs) | Any erythema | 5 Participants |
| Medium Dose_AS01E Group | Number of Participants With Any Solicited Administration Site Adverse Events (AEs) | Any swelling | 4 Participants |
| Medium Dose_AS01E Group | Number of Participants With Any Solicited Administration Site Adverse Events (AEs) | Any pain | 26 Participants |
Primary
Number of Participants With Any Solicited Systemic AEs
Assessed solicited systemic AE is fever (any temperature greater than or equal to 38.0 °C - the preferred location for measuring temperature being the oral cavity). Any is defined as occurrence of the symptom regardless of intensity grade or relation to study.
Time frame: During the 4-day follow-up period post-vaccination (i.e. on the day of vaccination [Day 1] and 3 subsequent days)
Population: The analysis was performed on the Exposed Set that included all participants who received the study intervention dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose_AS01E Group | Number of Participants With Any Solicited Systemic AEs | 1 Participants |
| Low Dose_AS01E Group | Number of Participants With Any Solicited Systemic AEs | 1 Participants |
| Medium Dose_AS01E Group | Number of Participants With Any Solicited Systemic AEs | 4 Participants |
Primary
Number of Participants With Any Unsolicited AEs
An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to study vaccination.
Time frame: During the 30-day follow-up period post-vaccination (i.e., on the day of vaccination [Day 1] and 29 subsequent days)
Population: The analysis was performed on the Exposed Set that included all participants who received the study intervention dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose_AS01E Group | Number of Participants With Any Unsolicited AEs | 5 Participants |
| Low Dose_AS01E Group | Number of Participants With Any Unsolicited AEs | 11 Participants |
| Medium Dose_AS01E Group | Number of Participants With Any Unsolicited AEs | 12 Participants |
Secondary
Frequency of RSVPreF3-specific Cluster of Differentiation 4+ (CD4+) T-cells Identified as Expressing at Least Two Markers
Among markers expressed are interleukin-2 (IL2), cluster of 40 ligand (CD40L), tumour necrosis factor alpha (TNF α) and interferon gamma (IFN γ), in vitro upon stimulation with RSVPreF3 peptide preparations.
Time frame: At 30 days post-vaccination (Day 31)
Population: The analysis was performed on the Per Protocol Set (that included participants who received the study intervention dose and have post-vaccination data, minus participants with protocol deviations that led to exclusion), for the High Dose\_AS01E Group only (as per protocol).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High Dose_AS01E Group | Frequency of RSVPreF3-specific Cluster of Differentiation 4+ (CD4+) T-cells Identified as Expressing at Least Two Markers | 1601 cells per million CD4+ T Cells |
Secondary
Humoral Immune Response in Terms of RSVPreF3-specific Immunoglobulin G (IgG) Antibody Concentrations
The detection and the quantification of total IgG antibodies directed against RSVPreF3 in human serum samples were based on an indirect Enzyme-Linked Immunosorbent Assay (ELISA). Anti RSVPreF3 antibody concentration is given in geometric mean concentration (GMC) and is expressed in ELISA Laboratory Units per milliliter (ELU/mL).
Time frame: At 30 days post-vaccination (Day 31)
Population: The analysis was performed on the Per Protocol Set (that included participants who received the study intervention dose and have post-vaccination data, minus participants with protocol deviations that led to exclusion), for the High Dose\_AS01E Group only (as per protocol).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| High Dose_AS01E Group | Humoral Immune Response in Terms of RSVPreF3-specific Immunoglobulin G (IgG) Antibody Concentrations | 46276.5 ELU/mL |
Secondary
Number of Participants Reporting pIMDs up to the End of Follow-up Study Period (Month 6)
pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
Time frame: From Day 1 up to the end of follow-up period (Month 6)
Population: The analysis was performed on the Exposed Set that included all participants who received the study intervention dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose_AS01E Group | Number of Participants Reporting pIMDs up to the End of Follow-up Study Period (Month 6) | 0 Participants |
| Low Dose_AS01E Group | Number of Participants Reporting pIMDs up to the End of Follow-up Study Period (Month 6) | 0 Participants |
| Medium Dose_AS01E Group | Number of Participants Reporting pIMDs up to the End of Follow-up Study Period (Month 6) | 0 Participants |
Secondary
Number of Participants With Any SAEs, up the End of Follow-up Study Period (Month 6)
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity.
Time frame: From Day 1 up to the end of follow-up period (Month 6)
Population: The analysis was performed on the Exposed Set that included all participants who received the study intervention dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose_AS01E Group | Number of Participants With Any SAEs, up the End of Follow-up Study Period (Month 6) | 1 Participants |
| Low Dose_AS01E Group | Number of Participants With Any SAEs, up the End of Follow-up Study Period (Month 6) | 1 Participants |
| Medium Dose_AS01E Group | Number of Participants With Any SAEs, up the End of Follow-up Study Period (Month 6) | 2 Participants |