A Study on the Immune Response, Safety and the Occurrence of Respiratory Syncytial Virus (RSV)-Associated Respiratory Tract Illness After Administration of RSV OA Vaccine in Adults 60 Years and Older

GlaxoSmithKline2,620 enrolled

Overview

The purpose of the current study is to evaluate the immune response of the RSVPreF3 OA investigational vaccine in older adults (OA) at least (\>=) 60 years of age (YOA) in China compared to OA in the same age range to be enrolled from overseas countries that participated in the RSV OA=ADJ-006 (NCT04886596) study, since the vaccine efficacy against lower respiratory tract disease (LRTD) has been demonstrated following a single dose of the RSVPreF3 OA investigational vaccine in the global efficacy study RSV OA=ADJ-006. In addition, the safety (in all participants) , reactogenicity and occurrence of RSV-associated acute respiratory illness (ARI) (in study participants in China only) after administration of the vaccine are also assessed in the current study. No ARI surveillance will be conducted for the overseas participants.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

2,620

Conditions

Respiratory Syncytial Virus Infections

Interventions

Eligibility

Sex: ALLMin age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Adult male or female of ≥60 YOA at the time of study intervention administration, who live in the community dwelling (CD participants). * 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, attend regular phone calls/study site visits, perform self-swabbing (study participants in China only), ability to access and utilize a phone or other electronic communications). * Participants who are medically stable in the opinion of the investigator at the time of vaccination. Participants 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 medically stable. * Written or witnessed informed consent obtained from the participant (participant must be able to understand the informed consent) prior to performance of any study specific procedure. Exclusion Criteria: Medical Conditions: * History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s). * Any clinical conditions for which serum samples would be prohibited for transfer to local central lab for testing. These clinical conditions include hepatitis B, hepatitis C, HIV and Syphilis based on medical history and physical examination (all participants) and laboratory screening tests (overseas participants). * Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., current malignancy, human immunodeficiency virus) or immunosuppressive/cytotoxic therapy (e.g., medication used during cancer chemotherapy, organ transplantation, or to treat autoimmune disorders), based on medical history and physical examination (no laboratory testing required). * Any history of dementia or any medical condition that moderately or severely impairs cognition. * Recurrent history or uncontrolled neurological disorders or seizures. 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 (e.g. completion of the diary cards, attend regular phone calls/study site visits, perform self-swabbing (study participants in China only). * Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival to less than 1 year). * Serious or unstable chronic illness. * Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. Prior/Concomitant Therapy: * Previous vaccination with RSV vaccine. * Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study intervention(s) during the period beginning 30 days before the dose of study intervention(s), or their 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 study intervention administration, with the exception of COVID-19 and inactivated/subunit influenza vaccines which can be administered up to 14 days before or from 14 days after each study intervention. * Administration of long-acting immune-modifying drugs or planned administration at any time during the study period (e.g., infliximab). * Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the study intervention administration 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 study intervention administration or planned administration during the study period. For corticosteroids, this will mean prednisone \>=20 mg/day, or equivalent. Inhaled and topical steroids are allowed. 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 intervention (drug/invasive medical device). Other Exclusion Criteria: * History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures. * Bedridden participants. * Planned move during the study conduct that prohibits participation until study end. * Participation of any study personnel or their immediate dependents, family, or household members.

Locations (40)

GSK Investigational Site

Shanghai, Putuo, China

GSK Investigational Site

Shanghai, Putuo, China

GSK Investigational Site

Shanghai, Shanghai Municipality, China

GSK Investigational Site

Shanghai, China

GSK Investigational Site

Shanghai, China

GSK Investigational Site

Outcomes

Primary Outcomes

RSV-A Neutralizing Titers Expressed as Adjusted Geometric Mean Titers (GMTs) at 1 Month Post RSVPreF3 OA Vaccination

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.

Time frame: At Day 31

Percentage of Participants With Seroresponse for RSV-A Neutralizing Titers at 1 Month Post RSVPreF3 OA Vaccination

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).

Time frame: At Day 31 compared to baseline (Day 1)

RSV-B Neutralizing Titers Expressed as Adjusted GMTs at 1 Month Post RSVPreF3 OA Vaccination

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.

Time frame: At Day 31

Percentage of Participants With Seroresponse for RSV-B Neutralizing Titers at 1 Month Post RSVPreF3 OA Vaccination

Time frame: At Day 31 compared to baseline (Day 1)

Secondary Outcomes

RSV-A Neutralizing Titers Expressed as Unadjusted GMTs at Baseline and 1 Month Post RSVPreF3 OA Vaccination

Neutralizing titers were measured with neutralization assay and the results were expressed as GMT. Unadjusted GMT is a descriptive statistic calculated directly from the observed titer values at pre-vaccination and at 1-month post-vaccination timepoints for all participants in the analysis set, without any statistical modelling or adjustment for covariates.

Time frame: At Day 1 (baseline) and Day 31 (1 month post RSVPreF3 OA vaccination)

RSV-B Neutralizing Titers Expressed as Unadjusted GMTs at Baseline and 1 Month Post RSVPreF3 OA Vaccination

Time frame: At Day 1 (baseline) and Day 31 (1 month post RSVPreF3 OA vaccination)

RSV-A and RSV-B Neutralizing Titers Expressed as Unadjusted GMTs at 6 Months Post RSVPreF3 OA Vaccination

Data not available at the time of initial results posting, will be updated at the final results disclosure stage.

Time frame: At Day 181 (6 months post RSVPreF3 OA vaccination)

Percentage of Participants With Seroresponse for RSV-A and RSV-B Neutralizing Titers at 1 Month Post RSVPreF3 OA Vaccination

Time frame: At Day 31 compared to baseline (Day 1)

Percentage of Participants With Seroresponse for RSV-A and RSV-B Neutralizing Titers at 6 Months Post RSVPreF3 OA Vaccination

Data not available at the time of initial results posting, will be updated at the final results disclosure stage.

Time frame: At Day 181 compared to baseline (Day 1)

RSV-A and RSV-B Neutralizing Titers Expressed as Adjusted GMTs at 1 Month Post RSVPreF3 OA Vaccination Between RSV OA Overseas (RSV OA=ADJ-006 Study) vs RSV OA Vaccine Group (China) Group

This outcome measure compares the adjusted GMTs for RSV-A and RSV-B for the RSV OA vaccine Group (China) to the selected immunogenicity subset of the global efficacy study RSV OA=ADJ-006 \[RSV OA Overseas (RSV OA=ADJ-006 study) group\]. 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.

Time frame: At Day 31

Percentage of Participants With Seroresponse for RSV-A and RSV-B Neutralizing Titers at 1 Month Post RSVPreF3 OA Vaccination Between RSV OA Overseas (RSV OA=ADJ-006 Study) vs RSV OA Vaccine Group (China) Group

This outcome measure compares the seroresponse for RSV-A and RSV-B neutralizing titers in the RSV OA vaccine Group (China) group to the selected immunogenicity subset of the global efficacy study RSV OA=ADJ-006 \[RSV OA Overseas (RSV OA=ADJ-006 study) group\].

Time frame: At Day 31 compared to baseline (Day 1)

Number of Participants With Real Time Polymerase Chain Reaction (RT-PCR) Confirmed RSV-A/B Associated Acute Respiratory Illness (ARI) and Lower Respiratory Tract Disease (LRTD) Cases

Data not available at the time of initial results posting, will be updated at the final results disclosure stage.

Time frame: From Day 15 and up to study end (6 months post dose [dose administered at Day 1])

Duration of Episodes for RSV-confirmed ARI and LRTD Cases

Data not available at the time of initial results posting, will be updated at the final results disclosure stage.

Time frame: From Day 15 and up to study end (6 months post dose [dose administered at Day 1])

Number of Episodes of Each of the Symptoms/Signs Associated to RSV-confirmed ARI Cases

Data not available at the time of initial results posting, will be updated at the final results disclosure stage.

Time frame: From Day 15 and up to study end (6 months post dose [dose administered at Day 1])

Number of Episodes of Each of the Symptoms/Signs Associated With RSV-confirmed LRTD Cases

Data not available at the time of initial results posting, will be updated at the final results disclosure stage.

Time frame: From Day 15 and up to study end (6 months post dose [dose administered at Day 1])

Number of Participants With RSV-confirmed ARI and LRTD Episodes by Severity

Data not available at the time of initial results posting, will be updated at the final results disclosure stage.

Time frame: From Day 15 and up to study end (6 months post dose [dose administered at Day 1])

Number of Participants With RSV-confirmed ARI and LRTD Cases by Frailty Status

Data not available at the time of initial results posting, will be updated at the final results disclosure stage.

Time frame: From Day 15 and up to study end (6 months post dose [dose administered at Day 1])

Number of Participants Reporting Any Solicited Administration Site Adverse Events

Assessed solicited administration site adverse events were pain, redness (erythema) and swelling at administration site. Any = occurrence of the symptom regardless of intensity grade.

Time frame: Day 1 (baseline) to Day 7

Number of Participants Reporting Any Solicited Systemic Adverse Events

Assessed solicited systemic adverse events were fever (pyrexia), headache, myalgia (muscle pain), arthralgia (joint pain) and fatigue (tiredness). Fever was defined as body temperature greater or equal to (≥) 38 degrees Celsius (ºC). Any = occurrence of the symptom regardless of intensity grade.

Time frame: Day 1 (baseline) to Day 7

Number of Participants Reporting Any Unsolicited Adverse Events (AEs)

An unsolicited AE was an AE that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Unsolicited AEs included both serious and non-serious AEs. Any = occurrence of the symptom regardless of intensity grade.

Time frame: Day 1 (baseline) to Day 30

Number of Participants Reporting Any Serious Adverse Events (SAEs), Related SAEs and Fatal SAEs up to Data Lock Point of Primary Analysis

An SAE is defined as any untoward medical occurrence that results in death, are life threatening, require hospitalization or prolongation of hospitalization or results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, is considered or defined as an important medical event, or abnormal pregnancy outcomes. Any SAE = occurrence of the SAE regardless of the intensity grade or relation to study vaccination. Related SAE = SAE assessed by the investigator as related to the study vaccination. Fatal SAE = occurrence of a fatal SAE regardless of relation to study vaccination.

Time frame: Day 1 (baseline) up to data lock point of primary analysis (median follow-up: 229 days [min.: 28 days, max.: 338 days)

Number of Participants Reporting Any SAEs, Related SAEs and Fatal SAEs up to End of Study

Data not available at the time of initial results posting, will be updated at the final results disclosure stage.

Time frame: Throughout the study period (up to 6 months post dose [administered at Day 1 (baseline)])

Number of Participants Reporting Any Potential Immune-mediated Disease (pIMDs) and Related pIMDs up to Data Lock Point for Primary Analysis

pIMDs are a subset of Adverse Events of Specific Interest (AESIs) that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. Any pIMDs = occurrence of the pIMDs regardless of the intensity grade or relation to study vaccination. Related pIMDs = pIMDs assessed by the investigator as related to the study vaccination.

Time frame: Day 1 (baseline) up to data lock point of primary analysis (median follow-up: 229 days [min.: 28 days, max.: 338 days)

Number of Participants Reporting Any pIMDs and Related pIMDs up to End of Study

Data not available at the time of initial results posting, will be updated at the final results disclosure stage.

Time frame: Throughout the study period (up to 6 months post dose [administered at Day 1 (baseline)])