mRNA Vaccine for RSV

Recruiting at 7 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: GlaxoSmithKline

Must not be taking: Immune-modifying drugs

Disqualifiers: Immunodeficient, HIV, HBV, HCV, others

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

Compensation: Varies

Number of Visits: 1

Duration: 19 months

210 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the reactogenicity, safety and immune response of various formulations of the RSV mRNA investigational vaccine administered in healthy participants 18-45 years of age.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use any investigational or non-registered products, or receive certain vaccines during the study period. Chronic use of immune-modifying drugs is also not allowed.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use any investigational or non-registered products, or chronic immune-modifying drugs during the study.

What data supports the idea that mRNA Vaccine for RSV (also known as: Investigational RSV vaccine, mRESVIA, ABRYSVO, AREXVY) is an effective treatment?

The available research shows that Arexvy and Abrysvo, which are vaccines for RSV, have been authorized by the US Food and Drug Administration to protect older adults from RSV-related illnesses. These vaccines are part of a new wave of treatments that include mRNA technology, which is also used in other vaccines like those for COVID-19. The research highlights that these vaccines are effective in preventing lower respiratory tract diseases in older adults, which is a significant health benefit. While the studies do not provide specific numbers, the authorization by the FDA suggests that they have been found effective in clinical trials. Additionally, Abrysvo is noted for its use in pregnant women to help protect infants, indicating its effectiveness in different age groups. ^{1 2 3 4 5}

What data supports the effectiveness of the mRNA vaccine for RSV?

The vaccines Arexvy and Abrysvo, which are part of the mRNA vaccine for RSV, have been authorized by the US FDA to protect older adults against RSV-related illnesses, indicating their effectiveness in preventing lower respiratory tract disease. ^{1 2 3 4 5}

What safety data is available for the mRNA RSV vaccine?

The provided research does not contain specific safety data for the mRNA RSV vaccine or its related names (mRESVIA, ABRYSVO, AREXVY). The studies focus on other vaccines, such as rotavirus, varicella, MMR, and COVID-19 mRNA vaccines, and their safety profiles. To find relevant safety data for the mRNA RSV vaccine, one would need to look for studies or reports specifically evaluating this vaccine. ^{6 7 8 9 10}

What safety data exists for mRNA vaccines, including those for RSV?

Overall, vaccines, including mRNA vaccines, have shown an exceptional safety profile with low rates of adverse events. Most reported reactions are typical and mild, similar to those seen with placebo injections, and serious adverse events are rare. ^{6 7 8 9 10}

Is the mRNA Vaccine for RSV a promising treatment?

Yes, the mRNA Vaccine for RSV, known as mRESVIA, ABRYSVO, or AREXVY, is a promising treatment. It is designed to protect against respiratory syncytial virus (RSV), which can cause serious illness in young children and older adults. The vaccine uses advanced technology to target the virus effectively, and it has shown positive results in clinical trials, making it a hopeful option for preventing RSV infections. ^{5 11 12 13 14}

How is the mRNA RSV vaccine different from other RSV treatments?

The mRNA RSV vaccine, such as mRESVIA, is unique because it uses mRNA technology to instruct cells to produce a part of the RSV virus, specifically the pre-fusion F protein, which helps the immune system recognize and fight the virus. This approach is different from traditional vaccines and is designed to provide targeted protection against RSV, especially in older adults and infants through maternal immunization. ^{5 11 12 13 14}

Eligibility Criteria

Healthy adults aged 18-45 who can consent, have a BMI of >=18 and <40 kg/m^2, are not pregnant or breastfeeding, agree to use contraception if applicable, and have no history of severe allergies or reactions to vaccines. Participants must not be using other investigational drugs or have certain chronic diseases.

Inclusion Criteria

Written informed consent must be obtained from the participant before any study-specific procedure.

Body mass index must be >= 18 kg/m^2 and < 40 kg/m^2.

I am a woman who cannot become pregnant.

Exclusion Criteria

I have previously received an RSV vaccine or treatment.

Concurrent participation in another clinical study involving investigational interventions.

History of reaction or hypersensitivity to study intervention components.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various doses of the mRNA-based RSV investigational vaccine

19 months

Multiple visits including Day 1, Day 8, Day 30, Day 37, Day 59, Month 7, Month 13, and Month 19

Follow-up

Participants are monitored for safety and immune response after vaccination

6 months

Treatment Details

Interventions

• Investigational RSV vaccine

Trial Overview The trial is testing the safety and immune response to different doses of an mRNA-based RSV vaccine in healthy participants. It compares several formulations against a placebo to find out which one works best without causing significant problems.

Participant Groups

Group I: RSV_Group F Experimental Treatment 2 Interventions

Group II: RSV_Group E Experimental Treatment 1 Intervention

Group III: RSV_Group D Experimental Treatment 1 Intervention

Group IV: RSV_Group C Experimental Treatment 1 Intervention

Group V: RSV_Group B Experimental Treatment 1 Intervention

Group VI: RSV_Group A Experimental Treatment 1 Intervention

Group VII: Placebo Group Placebo Group 1 Intervention

Investigational RSV vaccine is already approved in United States for the following indications:

Approved in United States as mRESVIA for:

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

Approved in United States as ABRYSVO for:

• Prevention of RSV-LRTD in adults aged 60 years and older
• Prevention of RSV-LRTD in infants through 6 months of age when administered to pregnant women at 32 to 36 weeks of gestation

Approved in United States as AREXVY for:

• Prevention of RSV-LRTD in adults aged 60 years 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

Findings from Research

The study evaluated an adjuvanted RSV vaccine in 1900 adults aged 60 and older, using a reliable patient-reported outcome tool (FLU-PRO) to assess RSV disease symptoms and virologic confirmation, demonstrating the tool's effectiveness in capturing relevant data.

Self-collection of nasal swabs significantly improved the detection of RSV cases, identifying 9 additional cases that site-swabbing alone would have missed, highlighting the importance of participant engagement in monitoring respiratory illnesses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation. Yu, J., Powers, JH., Vallo, D., et al.[2020]

The historical use of a formalin-inactivated RSV vaccine in the 1960s led to enhanced respiratory disease in infants, highlighting the need to understand the immunological mechanisms behind this adverse effect before developing new vaccines.

Recent discussions among experts and the FDA suggest that if new candidate vaccines demonstrate safety in preclinical and early clinical studies, they may be tested in RSV-naïve infants, marking a potential advancement in preventive measures against RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Summary of the Vaccines and Related Biological Products Advisory Committee meeting held to consider evaluation of vaccine candidates for the prevention of respiratory syncytial virus disease in RSV-naïve infants. Browne, SK., Beeler, JA., Roberts, JN.[2021]

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]

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 first vaccines for respiratory syncytial virus (RSV), Arexvy® and Abrysvo®, have been approved for use, targeting lower respiratory tract disease in older adults and providing passive immunity to infants through maternal vaccination.

There are currently 24 RSV vaccine candidates in clinical development, utilizing various technologies such as mRNA and live-attenuated vaccines, which allows for tailored approaches to protect different vulnerable age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory Syncytial Virus Vaccines: A Review of the Candidates and the Approved Vaccines. Topalidou, X., Kalergis, AM., Papazisis, G.[2023]

The analysis of the VAERS database for the year 1999 revealed that the tetra-valent rhesus-human reassortant rotavirus vaccine (RRV-TV) was associated with a statistically significant increase in serious gastrointestinal reactions compared to control vaccines like DTaP and OPV.

This study highlights the utility of the VAERS database in identifying potential risks associated with vaccines, suggesting that RRV-TV may elevate the risk of gastrointestinal adverse reactions in vaccinated children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal reactions and rotavirus vaccination based upon analysis of the Vaccine Adverse Events Reporting System (VAERS) database for 1999. A model for the calculation of the incidence rates and statistical significance of adverse events following immunization. Geier, DA., Geier, MR.[2004]

In a study analyzing 545,830 doses of the MMR vaccine administered over five years, only 96 adverse event notifications were reported, indicating a low incidence rate of 1.76 notifications per 100,000 doses.

The most common adverse events were mild, such as fever (42.7%) and local inflammation (36.5%), with all reported cases recovering completely, supporting the conclusion that the MMR vaccine has a good safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Suspected adverse events to measles, mumps and rubella vaccine reported to the Community of Valencia Pharmacovigilance Centre]. Pérez-Vilar, S., Gutiérrez-Gimeno, MV., Rodríguez-Galán, MA., et al.[2013]

From 2006 to 2020, the single-antigen varicella vaccine (VAR) and the combination measles, mumps, rubella, and varicella vaccine (MMRV) showed favorable safety profiles, with serious adverse events reported at rates of 1.3 per 100,000 doses for both vaccines.

The most common adverse events were mild, such as injection site reactions and fever, and no new or unexpected safety issues were identified, reinforcing the vaccines' safety when administered as recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Surveillance of Varicella Vaccines in the Vaccine Adverse Event Reporting System, United States, 2006-2020. Moro, PL., Leung, J., Marquez, P., et al.[2022]

The adverse event rate for vaccines is very low, with only about 11.4 reports per 100,000 vaccine doses, and less than 2% of these reports involve death, indicating a strong safety profile for vaccines.

Most reported adverse events are typical reactions to vaccinations and are similar in frequency to those seen with placebo injections, demonstrating that vaccines are generally safe and effective, with ongoing monitoring ensuring their safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine safety. Jacobson, RM.[2019]

Cardiac complications, particularly myopericarditis, were the most frequently reported severe adverse events associated with mRNA COVID-19 vaccines, with systemic reactions being more common after the second dose.

Despite the higher number of reported adverse effects following the Pfizer vaccine, the review concluded that the overall benefits of mRNA vaccines in controlling the COVID-19 pandemic significantly outweigh the risks of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Adverse Events Related to COVID-19 mRNA Vaccines; a Systematic Review. SeyedAlinaghi, S., Karimi, A., Pashaei, Z., et al.[2022]

The mRNA-1345 vaccine demonstrated high efficacy, with 83.7% effectiveness in preventing RSV-associated lower respiratory tract disease with at least two symptoms, and 68.4% efficacy against RSV-associated acute respiratory disease in a study involving 35,541 older adults.

The vaccine was generally safe, with most adverse reactions being mild to moderate and transient, although there was a higher incidence of local and systemic reactions compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults. Wilson, E., Goswami, J., Baqui, AH., et al.[2023]

Respiratory syncytial virus (RSV) poses a significant health risk not only to infants but also to older adults, prompting urgent vaccine development efforts, with 19 candidates currently in clinical trials.

Advancements in understanding the RSV surface fusion glycoprotein have led to innovative vaccine strategies, including particle-based, live-attenuated, subunit, and vector-based approaches, although past trial failures indicate the need for improved knowledge on immunological protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. Mazur, NI., Higgins, D., Nunes, MC., et al.[2023]

The mRNA-based vaccine V172, designed to target the pre-fusion form of the RSV F glycoprotein, was found to be safe and well-tolerated in a Phase 1 clinical trial involving 112 older adults and 48 younger adults, with common side effects being mild and manageable.

V172 induced higher neutralizing antibody levels compared to a previous vaccine candidate (V171.2) and demonstrated protective effects in an animal model, suggesting it could be an effective option for preventing RSV infections in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a stabilized RSV pre-fusion F mRNA vaccine: Preclinical studies and Phase 1 clinical testing in healthy adults. Nussbaum, J., Cao, X., Railkar, RA., et al.[2023]

Despite over 60 years of effort, the only current preventive measure against respiratory syncytial virus (RSV) in Canada is a monoclonal antibody for high-risk infants, highlighting the urgent need for an effective vaccine.

Recent advancements in cellular immunology and protein structure have led to 121 clinical trials by 16 organizations, focusing on various vaccine technologies, including live-attenuated and subunit-based vaccines, indicating a promising future for RSV prevention in the next decade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the respiratory syncytial virus vaccine candidate pipeline in Canada. Killikelly, A., Tunis, M., House, A., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Summary of the Vaccines and Related Biological Products Advisory Committee meeting held to consider evaluation of vaccine candidates for the prevention of respiratory syncytial virus disease in RSV-naïve infants. [2021]

3. United States 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. [2023]

4. United States 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. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Respiratory Syncytial Virus Vaccines: A Review of the Candidates and the Approved Vaccines. [2023]

6. Greece pubmed.ncbi.nlm.nih.gov

Gastrointestinal reactions and rotavirus vaccination based upon analysis of the Vaccine Adverse Events Reporting System (VAERS) database for 1999. A model for the calculation of the incidence rates and statistical significance of adverse events following immunization. [2004]

7. Spain pubmed.ncbi.nlm.nih.gov

[Suspected adverse events to measles, mumps and rubella vaccine reported to the Community of Valencia Pharmacovigilance Centre]. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Safety Surveillance of Varicella Vaccines in the Vaccine Adverse Event Reporting System, United States, 2006-2020. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Vaccine safety. [2019]

10. Iran pubmed.ncbi.nlm.nih.gov

Safety and Adverse Events Related to COVID-19 mRNA Vaccines; a Systematic Review. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. [2023]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of a stabilized RSV pre-fusion F mRNA vaccine: Preclinical studies and Phase 1 clinical testing in healthy adults. [2023]

14. Canada pubmed.ncbi.nlm.nih.gov

Overview of the respiratory syncytial virus vaccine candidate pipeline in Canada. [2021]