*RSV OA=ADJ-017
Research type
Research Study
Full title
A Phase III, open-label, randomized, controlled, multi-country study to evaluate the immune response, safety and reactogenicity of an RSVPreF3 OA investigational vaccine when co-administered with FLU aQIV (inactivated influenza vaccine – adjuvanted) in adults aged 65 years and above.
IRAS ID
1005817
Contact name
Contact email
Sponsor organisation
GlaxoSmithKline Biologicals SA
Eudract number
2022-000623-21
Research summary
Respiratory Syncytial Virus (RSV) is a highly contagious virus that causes respiratory infections in people of all ages. Mild cases present like a common cold. RSV can lead to serious complications such as pneumonia in older adults. RSV may also worsen some existing conditions such as chronic respiratory or heart diseases. Currently, there is no approved RSV vaccine.
This global research study will investigate if the protection and safety of the RSVPreF3 OA investigational vaccine is the same when administered at the same time as an approved Flu vaccine as it is when administered separately, in adults aged ≥65 years old.
Participants in the study, following provision of their consent, will initially undergo screening procedures to understand if they are eligible for participation in the study. All eligible patients will receive both vaccinations, investigational RSV vaccination and approved Flu vaccination but will be randomised to receive them either together at the first visit or at two separate visits 30 days apart. Participants who receive the vaccinations at the same time will be expected to return to the site for an additional visit 30 days after the vaccinations were administered and will have a follow-up call 6 months after the first visit. Participants who have the vaccinations at separate visits will have three visits in total, with each visit 30 days apart and a follow up call 7 months after the first visit. Participants will be asked to complete an electronic diary for at least 7 days after their vaccination to capture any side effects, and participants with side effects will be asked to complete the diary until this is resolved. Participants will have blood samples taken before and after each vaccination. About 60 of the first patients randomised in the UK and Spain who have the vaccinations separately will have additional blood samples taken at all visits and have an additional visit 15 days after the second vaccination.Summary of study results:
"Respiratory syncytial virus (RSV) is a major cause of acute respiratory illness. In addition to infants, people of advanced age and those with certain underlying medical conditions (e.g., chronic heart or lung disease and diabetes) are at increased risk for severe RSV disease. The adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA, Arexvy) was developed to protect older adults against RSV disease. In a phase 3 study (NCT04886596), over two RSV seasons in adults≥ 60 years of age (YOA), the vaccine demonstrated an acceptable safety profile, and was efficacious against RSV- related lower respiratory tract disease (LRTD).In addition, vaccine efficacy (VE) was shown for the target populations with the highest medical need and at the highest risk of developing (severe) RSV LRTD, including older adults with increased age (60-79 YOA), older adults with comorbidities or pre-frail older adults. The RSVPreF3 OA vaccine was approved for protection against LRTD caused by RSV in adults ≥60 YOA in over 40 countries; including the USA, UK and EU countries, under the tradename Arexvy.
Influenza and RSV viruses co-circulate, and in regions with temperate climates, seasonal epidemics of both viruses occur mainly during winter months. In these regions, seasonal influenza vaccination is therefore typically offered in early autumn, which is when RSV vaccination may also be recommended. Co-administration of influenza and RSV vaccines during a single consultation could help protect older adults against both infections, while reducing the number of doctor’s appointments, improving convenience, and thereby increasing vaccination coverage. However, for co-administration of two vaccines to be recommended, it should not impact the immunogenicity and safety of either vaccine.
In this study, we evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) (i.e., recommended FLU vaccine for those aged 65 years and over in the UK) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in adults ≥65 YOA. Participants received FLU-aQIV and RSVPreF3 OA either concomitantly (Co-Ad group) or sequentially, 1 month apart (Control group). The main objective of the study was to show that the immune responses to the vaccines when co-administered are not inferior compared to when they are administered separately. The study compared the antibody levels in terms of hemagglutination inhibition (HI) titers for each of the 4 FLU-aQIV strains and RSV-A and RSV-B neutralization titers, 1 month after-vaccination. Reactogenicity and safety were also assessed.
Overall, 1045 participants were vaccinated (Co-Ad group: 523; Control group: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for 3 of the 4 FLU strains (i.e., A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains), and RSV-A neutralization titers. Further assessment of immune response to the FLU vaccine concluded an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups.
In addition, co-administration of RSVPreF3 OA and FLU-aQIV was well tolerated and had an acceptable safety profile. Solicited systemic adverse events (AEs) (e.g., Arthralgia, Fatigue, Headache, Myalgia) were reported more frequently after co-administration than after each vaccine separately. However, this was not considered clinically relevant as no increase in severity or duration of these events was observed in the Co-Ad group. The rates of solicited administration-site AEs (e.g., Erythema, Pain, Swelling), unsolicited AEs, serious AEs, and potential Immune mediated diseases were generally balanced between the groups.
In summary, this study showed that the adjuvanted FLU-aQIV and RSVPreF3 OA vaccines can be co-administered in adults aged ≥65 years without clinically relevant interference with the immune responses to either vaccine and a clinically acceptable safety and reactogenicity profile. Given the seasonal overlap of these two infections, the ability to give both vaccines during a single doctor’s visit may improve convenience and increase uptake of both vaccines, ultimately reducing the high burden of both influenza and RSV disease among older adults."REC name
London - South East Research Ethics Committee
REC reference
22/FT/0095
Date of REC Opinion
24 Aug 2022
REC opinion
Further Information Favourable Opinion