Respiratory Syncytial Virus Infections
Conditions
Keywords
Respiratory syncytial virus (RSV), Older adults, Acute respiratory illness (ARI), Lower respiratory tract disease (LRTD), Immune response, Efficacy study, Safety study
Brief summary
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.
Interventions
BIOLOGICALRSVPreF3 OA investigational vaccine
One dose of the RSVPreF3 OA investigational vaccine is administered intramuscularly at Day 1.
One dose of placebo is administered intramuscularly at Day 1.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Data from study participants in China is collected in an observer-blind manner. The study is open labelled for overseas participants.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RSV-A Neutralizing Titers Expressed as Adjusted Geometric Mean Titers (GMTs) at 1 Month Post RSVPreF3 OA Vaccination | At Day 31 | 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. |
| Percentage of Participants With Seroresponse for RSV-A Neutralizing Titers at 1 Month Post RSVPreF3 OA Vaccination | At Day 31 compared to baseline (Day 1) | 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 Expressed as Adjusted GMTs at 1 Month Post RSVPreF3 OA Vaccination | At Day 31 | 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. |
| Percentage of Participants With Seroresponse for RSV-B Neutralizing Titers at 1 Month Post RSVPreF3 OA Vaccination | At Day 31 compared to baseline (Day 1) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RSV-A Neutralizing Titers Expressed as Unadjusted GMTs at Baseline and 1 Month Post RSVPreF3 OA Vaccination | At Day 1 (baseline) and Day 31 (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. |
| RSV-B Neutralizing Titers Expressed as Unadjusted GMTs at Baseline and 1 Month Post RSVPreF3 OA Vaccination | At Day 1 (baseline) and Day 31 (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. |
| RSV-A and RSV-B Neutralizing Titers Expressed as Unadjusted GMTs at 6 Months Post RSVPreF3 OA Vaccination | At Day 181 (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. |
| Percentage of Participants With Seroresponse for RSV-A and RSV-B Neutralizing Titers at 1 Month Post RSVPreF3 OA Vaccination | 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 | At Day 181 compared to baseline (Day 1) | Data not available at the time of initial results posting, will be updated at the final results disclosure stage. |
| 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 | At Day 31 | 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. |
| 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 | At Day 31 compared to baseline (Day 1) | 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 \[RSV OA Overseas (RSV OA=ADJ-006 study) group\]. |
| 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 | From Day 15 and up to study end (6 months post dose [dose administered at Day 1]) | Data not available at the time of initial results posting, will be updated at the final results disclosure stage. |
| Duration of Episodes for RSV-confirmed ARI and LRTD Cases | From Day 15 and up to study end (6 months post dose [dose administered at Day 1]) | Data not available at the time of initial results posting, will be updated at the final results disclosure stage. |
| Number of Episodes of Each of the Symptoms/Signs Associated to RSV-confirmed ARI Cases | From Day 15 and up to study end (6 months post dose [dose administered at Day 1]) | Data not available at the time of initial results posting, will be updated at the final results disclosure stage. |
| Number of Episodes of Each of the Symptoms/Signs Associated With RSV-confirmed LRTD Cases | From Day 15 and up to study end (6 months post dose [dose administered at Day 1]) | Data not available at the time of initial results posting, will be updated at the final results disclosure stage. |
| Number of Participants With RSV-confirmed ARI and LRTD Episodes by Severity | From Day 15 and up to study end (6 months post dose [dose administered at Day 1]) | Data not available at the time of initial results posting, will be updated at the final results disclosure stage. |
| Number of Participants With RSV-confirmed ARI and LRTD Cases by Frailty Status | From Day 15 and up to study end (6 months post dose [dose administered at Day 1]) | Data not available at the time of initial results posting, will be updated at the final results disclosure stage. |
| Number of Participants Reporting Any Solicited Administration Site Adverse Events | Day 1 (baseline) to Day 7 | Assessed solicited administration site adverse events were pain, redness (erythema) and swelling at administration site. Any = occurrence of the symptom regardless of intensity grade. |
| Number of Participants Reporting Any Solicited Systemic Adverse Events | Day 1 (baseline) to Day 7 | 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. |
| Number of Participants Reporting Any Unsolicited Adverse Events (AEs) | Day 1 (baseline) to Day 30 | 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. |
| Number of Participants Reporting Any Serious Adverse Events (SAEs), Related SAEs and Fatal SAEs up to Data Lock Point of Primary Analysis | Day 1 (baseline) up to data lock point of primary analysis (median follow-up: 229 days [min.: 28 days, max.: 338 days) | 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. |
| Number of Participants Reporting Any SAEs, Related SAEs and Fatal SAEs up to End of Study | Throughout the study period (up to 6 months post dose [administered at Day 1 (baseline)]) | Data not available at the time of initial results posting, will be updated at the final results disclosure stage. |
| Number of Participants Reporting Any Potential Immune-mediated Disease (pIMDs) and Related pIMDs up to Data Lock Point for Primary Analysis | Day 1 (baseline) up to data lock point of primary analysis (median follow-up: 229 days [min.: 28 days, max.: 338 days) | 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. |
| Number of Participants Reporting Any pIMDs and Related pIMDs up to End of Study | Throughout the study period (up to 6 months post dose [administered at Day 1 (baseline)]) | Data not available at the time of initial results posting, will be updated at the final results disclosure stage. |
Countries
China, Finland, Japan, Poland, South Korea, Spain, United Kingdom
Participant flow
Pre-assignment details
Analysis presented includes data up to Primary Completion. Additional results will be provided within one year of study completion.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 70.1 YEARS STANDARD_DEVIATION 6.7 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 3 Participants |
| Race/Ethnicity, Customized Asian | 1906 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants |
| Race/Ethnicity, Customized White | 707 Participants |
| Sex: Female, Male Female | 439 Participants |
| Sex: Female, Male Male | 1259 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 820 | 2 / 1,199 | 0 / 601 |
| other Total, other adverse events | 2 / 820 | 641 / 1,199 | 107 / 601 |
| serious Total, serious adverse events | 28 / 820 | 53 / 1,199 | 38 / 601 |
Outcome results
None listed