Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Adjuvanted RSVPreF3 vaccine, RSVPreF3 OA investigational vaccine, RSVPreF3 OA vaccine, RSVPreF3 OA investigational vaccine (GSK3844766A), RSVPreF3 OA Investigational Vaccine
Arexvy · 18 trials · 2 indications
The serum neutralizing titers are expressed in Estimated Dilution (ED60). The group GMT ratio will be evaluated for RSV-OA overseas group (from RSV OA-ADJ-021 study) over RSV AIR (from the current study).
The SRR is defined as the proportion of participants having a 4-fold increase in neutralizing titers. The group SRR difference will be evaluated for RSV-OA overseas group (from RSV OA-ADJ-021 study) minus RSV AIR (from the current study).
The serum neutralizing titers are expressed in ED60. The group GMT ratio will be evaluated for RSV-OA overseas group (from RSV OA-ADJ-021 study) over RSV AIR (from the current study).
The group SRR difference will be evaluated for RSV-OA overseas group (from RSV OA-ADJ-021 study) minus RSV AIR (from the current study).
RSV-A neutralizing titers are given as GMTs and are expressed as Estimated Dilution 60 (ED60).
RSV-A neutralizing titers are given as GMTs and are expressed as ED60.
RSV-B neutralizing titers are given as GMTs and are expressed as ED60.
RSV-A neutralizing titers were determined by neutralization assay and the results were expressed as GMTs. Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model includes treatment group as fixed effect, and the pre-dose log10-transformed titers as a covariate.
Seroresponse was defined as at least a 4 fold (≥4) increase in neutralizing titers (1 month post-study intervention administration over pre-study intervention administration).
RSV-B neutralizing titers were determined by neutralization assay and the results were expressed as GMTs. Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model includes treatment group as fixed effect, and the pre-dose log10-transformed titers as a covariate.
RSV-A neutralizing titers are given as group GMTs and are expressed as Estimated dilution 60 (ED60)
SRR is defined as the percentage of participants having a fold increase in neutralizing titers (1 month post-study intervention administration over pre-study intervention administration) ≥4. RSV-A neutralizing titers are expressed as ED60.
RSV-B neutralizing titers are given as group GMTs and are expressed as ED60.
SRR is defined as the percentage of participants having a fold increase in neutralizing titers (1-month post-study intervention administration over pre-study intervention administration) ≥ 4. RSV-B neutralizing titers are expressed as ED60.
RSV-A neutralizing titers were provided as group GMTs and expressed as estimated dilution 60 (ED60) titers. Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model adjusted for baseline differences (in the pre-dose titers) includes treatment group and age category (age at vaccination: 50-59, 60-69 or ≥70 years) as fixed effects, and the pre-dose log10-transformed titers as a covariate.
RSV-B neutralizing titers were provided as group GMTs and expressed as estimated dilution 60 (ED60) titers. Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model adjusted for baseline differences (in the pre-dose titers) includes treatment group and age category (age at vaccination: 50-59, 60-69 or ≥70 years) as fixed effects, and the pre-dose log10-transformed titers as a covariate.
SARS-CoV-2 Omicron XBB.1.5 neutralizing titers against the pseudovirus bearing S protein were provided as group GMTs and expressed as titers. The neutralizing titer was calculated as the reciprocal serum dilution corresponding to the 50% signal reduction (NT50). Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model adjusted for baseline differences (in the pre-dose titers) includes treatment group and age category (age at vaccination: 50-59, 60-69 or ≥70 years) as fixed effects, and the pre-dose log10-transformed titers as a covariate.
Anti-gE antibodies were measured with enzyme linked immunosorbent assay (ELISA) and the results were expressed as GMC, in milli international units per milliliter (mIU/mL).
Neutralizing titers were measured with neutralization assay and the results were expressed as GMT. The ED60 was defined as the dose that produced an effect in 60% of the population.
Neutralizing titers were measured with neutralization assay and the results were expressed as GMT. The ED60 was defined as the dose that produced an effect in 60% of the population.
The OP titers were measured with multiplexed opsonophagocytosis assay and the results were expressed as GMT for each of the pneumococcal vaccine serotype.
Neutralizing titers were measured with neutralization assay and the results were expressed in ED60.
Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were expressed in Estimated Dilution 60 (ED60) and were measured on blood samples collected from vaccinated subjects. The ANCOVA model used to calculate the adjusted GMTs for RSV-A neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult HA-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.
The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) greater than or equal to 4 (\>=4).
Serological assays for the determination of antibodies against RSV-B were performed by neutralization assay. The corresponding antibody titers were expressed in ED60. The ANCOVA model used to calculate the adjusted GMTs for RSV-B neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult HA-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.
The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) \>=4.
Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The corresponding antibody titers were expressed in ED60. The ANCOVA model used to calculate the adjusted GMTs for RSV-A neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult AIR-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.
The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) \>=4.
Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers were expressed in ED60. The ANCOVA model used to calculate the adjusted GMTs for RSV-B neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult AIR-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.
The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) \>=4.
HI titers were assessed against the Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata strains.
HI antibodies assessed were antibodies against the Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata flu strains.
RSV-A neutralizing antibodies were given as GMTs and expressed as Estimated Dilution 60 (ED60).
RSV B neutralizing antibodies are given as GMTs and expressed as Estimated Dilution 60 (ED60).
Enzyme-linked immunosorbent assay (ELISA) was used to assess the concentrations of IgG antibodies against RSV PreF3 in serum samples.
First episode of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated LRTD during the first season was assessed. The case definition for RSV-confirmed LRTD is as follows: Presence of at least one RSV-positive swab detected by RT-PCR.
The serum neutralization assay is a functional assay that measures the ability of serum antibodies to neutralize RSV-A entry and replication in a host cell line. The serum neutralizing antibody titer is expressed in ED60 (Estimated Dilution 60) and corresponds to the inverse of the interpolated serum dilution that yields a 60% reduction of the signal compared to a control without serum.
HI antibody titers were assessed for each of the Flu vaccine strains, namely Flu A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). The serum HI antibody titers are expressed in 1/Dilution (DIL) where DIL corresponds to the highest dilution that shows complete HI.
RSV-A neutralizing antibodies were given as GMTs and expressed as Estimated Dose: serum dilution giving a 60% reduction of the RSV plaques compared to a control without serum (ED60).
RSV-A neutralizing antibodies were given as GMTs and expressed as ED60.
RSV-A neutralizing antibodies were given as GMTs and expressed as ED60.
RSV-A neutralizing antibodies were given as GMTs and expressed as ED60.
RSV-B neutralizing antibodies measured as GMTs and expressed as ED60.
RSV-B neutralizing antibodies measured as GMTs and expressed as ED60.
RSV-B neutralizing antibodies measured as GMTs and expressed as ED60.
RSV-B neutralizing antibodies measured as GMTs and expressed as ED60.
MGI is defined as the geometric mean of the within participant ratios of two timepoints (ie., ratio of titers observed at Visit 1 over titers observed 30 days post last dose in the RSV OA=ADJ-023 parent study).
MGI is defined as the geometric mean of the within participant ratios of two timepoints (ie., ratio of titers observed at Visit 1 over titers observed 30 days post last dose in the RSV OA=ADJ-023 parent study).
MGI was defined as the geometric mean of the within-participant ratios of serum neutralizing titers against RSV-A post-Dose 2 (Visit 4) over post-Dose 1 (Visit 3).
MGI was defined as the geometric mean of the within-participant ratios of serum neutralizing titers against RSV-B post-Dose 2 (Visit 4) over post-Dose 1 (Visit 3).
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).
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.
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.
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.
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.
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).
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.
| Arm | Type | Description |
|---|---|---|
| RSV AIR group | EXPERIMENTAL | Participants at increased risk (AIR) of RSV disease will receive a single dose of investigational RSVPreF3 OA investigational vaccine on Visit 1 (Day 1). |
| Placebo AIR group | PLACEBO_COMPARATOR | Participants AIR of RSV disease will receive a single dose of Placebo on Visit 1 (Day 1). |
| OA-RSV group | EXPERIMENTAL | Older adult (OA) participants, greater than or equal to (≥) 60 years of age (YOA), received a single dose of RSVPreF3 OA investigational vaccine at Day 1. |
| OA-Placebo group | PLACEBO_COMPARATOR | OA participants, ≥ 60 YOA, received a single dose of placebo at Day 1. |
| Adults-AIR-RSV group | EXPERIMENTAL | Adult participants, 50-59 YOA, at increased risk (AIR) of Respiratory Syncytial Virus - Lower Respiratory Tract Disease (RSV-LRTD), received a single dose of RSVPreF3 OA investigational vaccine at Day 1. |
| Adults-AIR-Placebo group | PLACEBO_COMPARATOR | Adult participants, 50-59 YOA, at increased risk (AIR) of RSV-LRTD, received a single dose of placebo at Day 1. |
| RSV OA vaccine Group (Overseas) | EXPERIMENTAL | Overseas older adults (OA) participants received a single dose of RSVPreF3 OA investigational vaccine at Day 1 and were followed up until end of study (Month 6). |
| RSV OA vaccine Group (China) | EXPERIMENTAL | Chinese OA participants received a single dose of RSVPreF3 OA investigational vaccine at Day 1 and were followed up until end of study (Month 6 or last acute respiratory illness (ARI) visit/contact, whichever was later). |
| Placebo Group (China) | EXPERIMENTAL | Chinese OA participants received a single dose of placebo at Day 1 and were followed up until end of study (Month 6 or last ARI visit/contact, whichever was later). |
| RSV_PreS4 | EXPERIMENTAL | Participants in this group will receive 1 dose of RSVPreF3 OA vaccine before RSV Season 4. |
| RSV_PreS5 | EXPERIMENTAL | Participants in this group will receive 1 dose of RSVPreF3 OA vaccine before RSV Season 5. |
| RSV_1Dose | NO_INTERVENTION | Participants in this group will not receive any additional dose of RSV PreF3 OA vaccine. |
| Crossover | EXPERIMENTAL | Participants in this group will receive a single dose of RSVPreF3 OA vaccine. |
| Part A: RSV-A-AIR Group | EXPERIMENTAL | Adult (A) participants, 18-49 YOA, at increased risk (AIR) for RSV disease, received a single dose of RSVPreF3 OA investigational vaccine at Day 1. Participants in this group were considered for all study analyses, as per protocol. |
| Part A: RSV-OA Group | ACTIVE_COMPARATOR | Older adults (OA) participants, ≥60 YOA, received a single dose of RSVPreF3 OA investigational vaccine at Day 1. |
| Part B: RSV-A-AIR Group | EXPERIMENTAL | Adult participants, 18-49 YOA, AIR for RSV disease, received a single dose of RSVPreF3 OA investigational vaccine at Day 1. Participants in this group were considered only for Participant flow, Baseline Characteristics and all safety analyses, as per protocol. |
| Co-Ad Group | EXPERIMENTAL | Participants received a single dose of RSVPreF3 OA vaccine and a single dose of COVID-19 mRNA vaccine at Day 1, in different arms. |
| Control Group | ACTIVE_COMPARATOR | Participants received a single dose of COVID-19 mRNA vaccine at Day 1, followed by a single dose of RSVPreF3 OA vaccine at Day 31. |
| Co-administration Group | EXPERIMENTAL | Participants received both herpes zoster recombinant subunit (HZ/su) vaccine and respiratory syncytial virus prefusion protein 3 older adult (RSVPreF3 OA) vaccine on Day 1 followed by second dose of HZ/su vaccine on Day 61. |
| Adults HA-RSV Group | EXPERIMENTAL | Healthy adults or adults with chronic stable conditions with or without treatment that do not lead to an increased risk of RSV-Lower respiratory tract disease (RSV-LRTD), aged 50-59 years old received 1 dose of RSVPreF3 OA vaccine at Day 1 and were followed until study end. |
| Adults HA-Placebo Group | PLACEBO_COMPARATOR | Healthy adults or adults with chronic stable conditions with or without treatment that do not lead to an increased risk of RSV-LRTD, aged 50-59 years old received 1 dose of placebo at Day 1 and were followed until study end. |
| Adults AIR-RSV Group | EXPERIMENTAL | Adults at increased risk of RSV-Lower respiratory tract disease (RSV-LRTD) aged 50-59 years old received 1 dose of RSVPreF3 OA vaccine at Day 1 and were followed until study end. |
| Adults AIR-Placebo Group | PLACEBO_COMPARATOR | Adults at increased risk of RSV-LRTD aged 50-59 years old received 1 dose of placebo at Day 1 and were followed until study end. |
| RSV OA_Lot 1 | EXPERIMENTAL | Participants received 1 dose of a combination of the RSVPreF3 antigen Lot 1 and AS01E adjuvant Lot A at Day 1 and were followed up until the study end (Month 6). |
| RSV OA_Lot 2 | EXPERIMENTAL | Participants received 1 dose of a combination of the RSVPreF3 antigen Lot 2 and AS01E adjuvant Lot B at Day 1 and were followed up until the study end (Month 6). |
| RSV OA_Lot 3 | EXPERIMENTAL | Participants received 1 dose of a combination of the RSVPreF3 antigen Lot 3 and AS01E adjuvant Lot C at Day 1 and were followed up until the study end (Month 6). |
| RSVPreF3 Group | EXPERIMENTAL | Participants received a single dose of the RSVPreF3 OA vaccine at Day 1. Before the second vaccination participants in this group were re-randomized into 2 as: a group that received placebo every subsequent year, and a group that received an additional dose of RSVPreF3 OA vaccine every subsequent year of the study. |
| Placebo Group | PLACEBO_COMPARATOR | Participants received 1 dose of placebo at Day 1 and an additional dose of placebo every subsequent year of the study. |
| RSV_annual Group | EXPERIMENTAL | Participants receive one dose of RSVPreF3 OA investigational vaccine at Day 1 and 2 revaccination doses at 12 months post-Dose 1 and at 24 months post-Dose 1, respectively and are followed up until Month 60. |
| RSV_Flexible revaccination Group | EXPERIMENTAL | Participants receive one dose of RSVPreF3 OA investigational vaccine at Day 1 and 2 revaccination doses at 24 months post-Dose 1 and at 48 months post-Dose 1, respectively and are followed up until Month 60. |
| RSV_1dose Group | EXPERIMENTAL | Participants receive one dose of RSVPreF3 OA investigational vaccine at Day 1 and are followed up until Month 36. At Month 36, participants in this group will be re-randomized in 2 groups: RSV\_1dose\_M36 (which will receive 1 additional revaccination dose at Month 36 and will be followed up until Month 60) and RSV\_1dose\_Flexible (which will receive 1 additional revaccination dose at Month 60, and will be followed up until study end at Month 72). |
| IC Revaccination Group | EXPERIMENTAL | Lung or kidney transplant recipients undergoing chronic immunosuppressive therapy who received 1 and 2 doses of the adjuvanted RSVPreF3 vaccine (IC\_1 and IC\_2 groups respectively) in the RSV OA=ADJ-023 parent study will receive a revaccination dose of adjuvanted RSVPreF3 vaccine at Visit 1 (Day 1) in the current study. |
| RSV_IC_1 group | EXPERIMENTAL | Immunocompromised (IC) participants (recipients of lung or renal transplant) received 1 dose of RSVPreF3 OA investigational vaccine at Visit 1 (Day 1). |
| RSV_IC_2 group | EXPERIMENTAL | IC participants (recipients of lung or renal transplant) received 2 doses of RSVPreF3 OA investigational vaccine at Visit 1 (Day 1) and Visit 3 (Visit 1 + 30-60 days). |
| RSV_HA group | ACTIVE_COMPARATOR | Healthy adult (HA) participants received 1 dose of RSVPreF3 OA investigational vaccine at Visit 1 (Day 1). |
| Group High Dose_Adjuvanted | EXPERIMENTAL | Participants in one of the high dose adjuvanted groups in part B of the parent study RSV OA=ADJ-002: Group High Dose Adjuvanted will receive one revaccination dose of the RSVPreF3 OA investigational vaccine in the current study by intramuscular (IM) injection in the non-dominant arm. |
| Group Medium Dose_Adjuvanted | EXPERIMENTAL | Participants in one of the medium dose adjuvanted groups in part B of the parent study RSV OA=ADJ-002: Group Medium Dose Adjuvanted will receive one revaccination dose of the RSVPreF3 OA investigational vaccine in the current study by IM injection in the non-dominant arm. |
| Group Low Dose_Adjuvanted | EXPERIMENTAL | Participants in one of the low dose adjuvanted groups in part B of the parent study RSV OA=ADJ-002: Group Low Dose Adjuvanted will receive one revaccination dose of the RSVPreF3 OA investigational vaccine in the current study by IM injection in the non-dominant arm. |
| Name | Type | Description |
|---|---|---|
| RSVPreF3 OA vaccine | BIOLOGICAL | 1 dose of RSVPreF3 OA investigational vaccine administered intramuscularly in the deltoid region of the non-dominant arm. |
| Placebo | BIOLOGICAL | 1 dose of saline solution administered intramuscularly in the deltoid region of the non-dominant arm. |
| RSVPreF3 OA investigational vaccine | BIOLOGICAL | 1 dose of RSVPreF3 OA investigational vaccine administered intramuscularly on Day 1 to participants in OA-RSV and Adults-AIR-RSV groups. |
| Placebo (Saline solution) | DRUG | One dose of placebo is administered intramuscularly at Day 1. |
| COVID-19 mRNA vaccine | BIOLOGICAL | 1 dose of COVID-19 mRNA vaccine is administered intramuscularly on Day 1 to participants in the Co-ad and Control Groups. |
| HZ/su vaccine | BIOLOGICAL | Two doses of HZ/su vaccine given intramuscularly on Day 1 and Day 61. |
| PCV20 | BIOLOGICAL | One dose of the 20-valent pneumococcal conjugate vaccine (PCV20) given intramuscularly in participant's dominant arm (Coad group) or non-dominant arm (Control group) on Day 1 |
| FLU HD vaccine | BIOLOGICAL | FLU HD vaccine administered intramuscularly in the deltoid region of the dominant arm (Co-Ad Group) or the non-dominant arm (Control Group). |
| FLU vaccine | BIOLOGICAL | One dose of FLU vaccine administered intramuscularly. |
| FLU-QIV | BIOLOGICAL | FLU-QIV administered intramuscularly in the deltoid region of the dominant (Co-Ad Group) arm or the non-dominant (Control Group) arm. |
| Adjuvanted RSVPreF3 vaccine | BIOLOGICAL | 1 dose of adjuvanted RSVPreF3 vaccine administered intramuscularly at Visit 1 (Day 1). |
| RSVPreF3 OA investigational vaccine (GSK3844766A) | BIOLOGICAL | 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). |
Inclusion Criteria: * Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol. * Written or witnessed informed consent obtained from the participant (participant must be able to understand the informed consent) prior to performance of any stud...