RSV Vaccine for Adults 60+

(RSV OA=ADJ=012 Trial)

Recruiting at 218 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must not be taking: Immunosuppressants, Immune-modifying drugs

Disqualifiers: Immunodeficient conditions, Serious illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

10356 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a vaccine called RSVPreF3 OA (also known as Arexvy) to determine its duration of effectiveness and safety for adults aged 60 and older. Researchers aim to identify the optimal timing for revaccination and assess whether the vaccine provides protection through up to five RSV seasons, a virus causing lung infections. The trial includes participants who previously received a placebo or a single dose of the RSVPreF3 OA vaccine in an earlier study. Individuals with stable medical conditions like diabetes or high blood pressure may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new vaccine.

Do I need to stop my current medications for the RSV vaccine trial?

The trial does not specify that you need to stop taking your current medications. However, if you are on immunosuppressants or immune-modifying drugs, you may need to stop them 90 days before the study starts. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the RSVPreF3 OA vaccine is generally safe for people aged 60 and older. Studies found that a single dose of this vaccine is well-tolerated. Over 15,000 participants received the RSVPreF3 OA vaccine, and safety data from these studies indicate that the vaccine is safe to use.

Most participants experienced only mild side effects, such as soreness at the injection site or slight fatigue. Serious side effects were rare. Receiving another dose a year later was also well-tolerated.

In summary, research suggests that the RSVPreF3 OA vaccine is safe for older adults, with only minor side effects commonly reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for RSV?

Researchers are excited about the RSVPreF3 OA vaccine for adults 60+ because it targets RSV, a common respiratory virus, with a novel approach. Unlike traditional vaccines that use inactivated or weakened viruses, RSVPreF3 OA is designed to trigger an immune response by using a pre-fusion protein structure, which is key to the virus's ability to infect cells. This approach could potentially offer stronger and longer-lasting protection. Additionally, the vaccine is administered as a single dose, which could simplify vaccination schedules and improve compliance compared to multi-dose vaccines.

What evidence suggests that the RSVPreF3 OA vaccine could be effective for adults 60+?

Research has shown that the RSVPreF3 OA vaccine helps prevent illnesses caused by RSV in older adults. One study found that a single dose of this vaccine was 67.2% effective in preventing lung infections caused by RSV over two seasons. It was also 78.8% effective against severe cases of these infections during the same period. Additional studies confirm that the vaccine reduces the risk of RSV infections requiring medical attention by 77.5%. In this trial, participants will receive different dosing schedules of the RSVPreF3 OA vaccine, or no additional dose, to evaluate its effectiveness further. These findings suggest that the RSVPreF3 OA vaccine can significantly lower the chances of serious RSV-related breathing problems in adults aged 60 and over. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 60 and above who previously took part in the RSV OA=ADJ-006 study. It's designed to assess the timing for a second vaccine dose, long-term safety, and immune response over approximately five RSV seasons.

Inclusion Criteria

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, ability to access and utilize a phone or other electronic communications)

Written or witnessed informed consent obtained from the participant prior to performance of any study specific procedure

I was in the RSV OA=ADJ-006 study and received either a placebo or one dose of the RSVPreF3 OA vaccine.

Exclusion Criteria

History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention

Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study

Any history of dementia or any medical condition that moderately or severely impairs cognition and understanding of the informed consent form and/or study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Revaccination

Participants receive a dose of RSVPreF3 OA vaccine before RSV Season 4 or 5, or a single dose in the crossover group

1 week

1 visit (in-person)

Long-term Follow-up

Participants are monitored for immune persistence and safety up to 5 consecutive RSV seasons

60 months

What Are the Treatments Tested in This Trial?

Interventions

• RSVPreF3 OA vaccine

Trial Overview The study tests the RSVPreF3 OA vaccine's effectiveness in preventing Respiratory Syncytial Virus (RSV). Participants will either receive a follow-up dose or their first actual vaccine if they initially received a placebo.

How Is the Trial Designed?

Group I: RSV_PreS5 Experimental Treatment 1 Intervention

Participants in this group will receive 1 dose of RSVPreF3 OA vaccine before RSV Season 5.

Group II: RSV_PreS4 Experimental Treatment 1 Intervention

Participants in this group will receive 1 dose of RSVPreF3 OA vaccine before RSV Season 4.

Group III: Crossover Experimental Treatment 1 Intervention

Participants in this group will receive a single dose of RSVPreF3 OA vaccine.

Group IV: RSV_1Dose Active Control 1 Intervention

Participants in this group will not receive any additional dose of RSV PreF3 OA vaccine.

RSVPreF3 OA vaccine is already approved in United States for the following indications:

Approved in United States as Arexvy for:

• Prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in individuals 60 years of age and older

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

The recombinant subunit vaccine (RZV) is strongly recommended for individuals over 50 years old to prevent herpes zoster (HZ) and is more effective than the live attenuated zoster vaccine (LZV), especially as its efficacy declines more slowly with age.

Both vaccines are safe and cost-effective, but RZV is preferred due to its higher efficacy and longer-lasting protection against HZ and post-herpetic neuralgia, making it a better option for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Summary of the NACI Update on Herpes Zoster Vaccines. Warrington, R., Ismail, S.[2023]

Recombinant zoster vaccine (RZV) showed significantly higher efficacy than zoster vaccine live (ZVL) in preventing herpes zoster among immunocompetent individuals, with a relative vaccine efficacy of 84% and effectiveness of 49% based on 17 randomized controlled trials and 19 cohort studies.

RZV was also effective in immunocompromised subjects, demonstrating a 60% efficacy compared to placebo, and was well-tolerated with no increase in serious adverse events, making it a safer option than ZVL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, effectiveness, and safety of herpes zoster vaccine in the immunocompetent and immunocompromised subjects: A systematic review and network meta-analysis. Xia, Y., Zhang, X., Zhang, L., et al.[2022]

Continuous combined hormone replacement therapy (ccHRT) using estradiol valerate and medroxyprogesterone acetate significantly reduced the frequency of moderate to severe hot flushes by over 70% within one month in early postmenopausal women, based on a study of 459 participants over 52 weeks.

While ccHRT was effective and well tolerated, the highest dose regimen resulted in more adverse events compared to lower doses, indicating a need for careful dose management to balance efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of continuous combined hormone replacement therapy in early postmenopausal women. Mattsson, LA., Skouby, S., Rees, M., et al.[2018]

The investigational RSVPreF3/AS01B vaccine was found to be well tolerated in older adults (aged 60-80), with no serious adverse events reported among recipients, although solicited adverse events were more common compared to the placebo group.

The vaccine demonstrated strong immunogenicity, significantly increasing RSV-specific IgG antibody concentrations and neutralizing antibody titers against RSV-A and RSV-B, indicating its potential effectiveness in providing protection against respiratory syncytial virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a respiratory syncytial virus prefusion F protein (RSVPreF3) candidate vaccine in older Japanese adults: A phase I, randomized, observer-blind clinical trial. Kotb, S., Haranaka, M., Folschweiller, N., et al.[2023]

Vaccination with Arexvy and Abrysvo can significantly reduce the health burden of respiratory syncytial virus (RSV) in older adults, leading to fewer hospitalizations and deaths, making it a valuable intervention for this age group.

The cost-effectiveness analysis suggests that these vaccines could be economically viable, with a maximum price-per-dose of $127 for Arexvy and $118 for Abrysvo, potentially rising to $235 and $245 respectively if benefits extend into a second RSV season.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Prefusion F Protein-based Vaccines Against Respiratory Syncytial Virus Disease for Older Adults in the United States. Moghadas, SM., Shoukat, A., Bawden, CE., et al.[2023]

Revaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in elderly individuals (aged 70 and above) who had previously received the vaccine at least 5 years prior resulted in significant increases in immune responses, similar to those seen after the initial vaccination.

The study found that revaccination was well tolerated, with mild to moderate injection-site adverse events being more common than in the primary vaccination group, but not clinically significant, indicating that revaccination can be safely implemented to enhance protection against pneumococcal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revaccination with 23-valent pneumococcal polysaccharide vaccine in the Japanese elderly is well tolerated and elicits immune responses. Kawakami, K., Kishino, H., Kanazu, S., et al.[2017]

The recombinant adjuvanted zoster vaccine (RZV, Shingrix) is highly recommended for adults aged 50 and older to prevent herpes zoster and its complications, highlighting its efficacy in this age group.

The review also emphasizes the importance of proper administration and safety measures, particularly in special populations, to ensure effective vaccination and minimize errors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which patients should receive the herpes zoster vaccine? Short, MD., Fergus, C.[2020]

The RSVpreF vaccine candidate was found to be safe and well-tolerated in older adults (ages 65-85), eliciting strong and lasting immune responses against the respiratory syncytial virus, regardless of the formulation used.

Adding the adjuvant CpG/Al(OH)3 did not enhance the immune response compared to the standard aluminum hydroxide adjuvant, and most side effects were mild, indicating that the vaccine is a promising option for protecting older adults from RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine With and Without Adjuvant in Healthy Older Adults. Baber, J., Arya, M., Moodley, Y., et al.[2023]

The RSVPreF3 OA vaccine demonstrated high efficacy against RSV-related lower respiratory tract disease (94.6%) and acute respiratory illness (81.0%) in older adults with coexisting cardiorespiratory or endocrine/metabolic conditions, indicating it is effective for those at higher risk.

Immunogenicity results showed that post-vaccination neutralizing antibody levels in participants with these conditions were comparable to those without, suggesting that the vaccine is safe and effective across different health statuses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory Syncytial Virus Prefusion F Protein Vaccine Is Efficacious in Older Adults With Underlying Medical Conditions. Feldman, RG., Antonelli-Incalzi, R., Steenackers, K., et al.[2023]

The Ad26.RSV.preF vaccine demonstrated significant efficacy in preventing respiratory syncytial virus (RSV) infections in older adults, highlighting its potential as a protective measure in this vulnerable population.

The study also reported a favorable safety profile for the vaccine, indicating that it can be administered with minimal adverse effects, making it a promising option for older adults at risk for RSV-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In older adults, an Ad26.RSV.preF-RSV preF protein vaccine reduced RSV-related lower respiratory tract disease. Awar, M., Mylonakis, E.[2023]

Vaccination with the RSV vaccines Arexvy and Abrysvo can significantly reduce the health burden of RSV-related illnesses in older adults, providing substantial health benefits.

The cost-effectiveness analysis suggests that these vaccines are economically viable if priced under $120 per dose for Arexvy and $111 for Abrysvo, with potential budget impacts of up to $6.10 billion in the first RSV season.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Prefusion F Protein-Based Vaccines Against Respiratory Syncytial Virus Disease for Older Adults in the United States. Moghadas, SM., Shoukat, A., Bawden, CE., et al.[2023]

The RSVPreF3 vaccine combined with the AS01 adjuvant significantly boosted RSV-neutralizing antibody responses and T cell responses in both mice and cattle, indicating its potential effectiveness for older adults.

In both animal models, the RSVPreF3/AS01 formulation outperformed non-adjuvanted versions in generating stronger immune responses, suggesting it is a promising candidate for further clinical evaluation as a vaccine for RSV in older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of an AS01-adjuvanted respiratory syncytial virus prefusion F (RSVPreF3) vaccine in animal models. Bouzya, B., Rouxel, RN., Sacconnay, L., et al.[2023]

In a study involving 122 older adults, a third dose of the RSVPreF3-AS01E vaccine was found to be well tolerated, with mostly mild-to-moderate side effects and no serious adverse events reported, indicating a good safety profile.

The third dose significantly boosted RSV-specific neutralizing antibodies and T-cell responses, demonstrating its immunogenicity, although the antibody levels after the third dose were lower than those observed one month after the first dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Revaccination With a Respiratory Syncytial Virus Prefusion F Vaccine in Older Adults: A Phase 2b Study. Leroux-Roels, I., Van Ranst, M., Vandermeulen, C., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38253338/

Efficacy and Safety of Respiratory Syncytial Virus (RSV) ... Efficacy over 2 seasons of 1 RSVPreF3 OA dose was 67.2% (97.5% CI: 48.2-80.0%) against RSV-LRTD and 78.8% (95% CI: 52.6-92.0%) against severe ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2209604

Respiratory Syncytial Virus Prefusion F Protein Vaccine in ... A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile and prevented RSV-related acute respiratory infection and lower respiratory tract ...

3. cdc.gov cdc.gov/acip/grade/GSK-Adjuvanted-RSVPreF3-adults.html

GSK RSVPreF3 Vaccine (AREXVY) | ACIP GSK RSVPreF3 also reduced the risk of medically attended RSV LRTD (vaccine efficacy: 77.5% [95% CI: 57.9%, 89.0%]) (Table 3b). The trial was not ...

4. thelancet.com thelancet.com/journals/lanres/article/PIIS2213-2600(25)00048-7/abstract

Efficacy, safety, and immunogenicity of ... A single RSVPreF3 OA dose was efficacious against RSV-LRTD over three RSV seasons in people aged 60 years or older, despite a decrease in ...

5. academic.oup.com academic.oup.com/cid/article/78/6/1732/7585312

Efficacy and Safety of Respiratory Syncytial Virus (RSV ... Efficacy over 2 seasons of 1 RSVPreF3 OA dose was 67.2% (97.5% CI: 48.2–80.0%) against RSV-LRTD and 78.8% (95% CI: 52.6–92.0%) against severe RSV-LRTD.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04886596

NCT04886596 | Efficacy Study of GSK's Investigational ... This study evaluates the efficacy of an RSV vaccine in adults 60+ to prevent Lower Respiratory Tract Disease (LRTD) caused by RSV. It is a Phase 3, randomized, ...

7. cdc.gov cdc.gov/vaccines/vpd/rsv/hcp/older-adults.html

RSV Vaccination for Adults 60 Years of Age and Over CDC recommends only a single dose of an age-appropriate RSV vaccine for all adults ages 75 and older and for adults ages 50–74 with increased risk of severe RSV ...

8. fda.gov fda.gov/media/165621/download

Vaccines and Related Biological Products Advisory ... the RSVPreF3 OA vaccine has a clinically acceptable safety profile in adults ≥60 YOA. ... Based on the safety data from over 15,000 RSVPreF3 OA ...