RSV Vaccine for Infants and Toddlers

(PEARL Trial)

Recruiting at 255 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi Pasteur, a Sanofi Company

Must not be taking: Immunosuppressants, Corticosteroids, others

Disqualifiers: Immunodeficiency, Wheezing, Chronic illness, others

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

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

6300 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a phase III, randomized, observer-blind, placebo-controlled, multinational, multi-center study to be conducted in approximately 6300 children 6 months to \< 22 months of age. The purpose of the study is to evaluate the efficacy, immunogenicity, and safety of Respiratory Syncytial Virus Toddler (RSVt) vaccine administered by intranasal route compared to placebo. Eligible participants will be randomized in a 1:1 ratio to receive 2 intranasal administrations of either the RSVt vaccine or placebo. Study duration will be 24 months for each participant. The safety follow-up will start after the first vaccination and up to the end of the study.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot participate if you have received immunosuppressive therapy, long-term systemic corticosteroids, or certain vaccines recently. Check with the trial team for specific guidance.

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 participate if you have taken certain vaccines or medications recently, like intranasal medications within 3 days before the study or certain vaccines within 28 days before and after the first dose.

What data supports the idea that RSV Vaccine for Infants and Toddlers is an effective treatment?

The available research shows that while there is significant interest and ongoing development in creating an RSV vaccine for infants and toddlers, there is currently no effective vaccine available. The research highlights the challenges in developing a safe and effective vaccine, with many candidates still in the development stages. Alternative treatments, like the monoclonal antibody palivizumab, are available but are limited to high-risk infants due to cost and practicality issues. Therefore, there is no data supporting the effectiveness of an RSV vaccine for infants and toddlers at this time. ^{1 2 3 4 5}

What data supports the effectiveness of the RSVt Vaccine treatment for infants and toddlers?

Research indicates that there are promising RSV vaccine candidates in development, including those that have shown the ability to induce protective immunity without causing enhanced disease. Additionally, protein-based vaccines have been evaluated in clinical trials and are promising for providing early life protection. ^{1 2 3 4 6}

What safety data exists for the RSV vaccine for infants and toddlers?

The development of RSV vaccines has faced challenges, with some early candidates causing adverse effects. Recent efforts focus on creating safe and effective vaccines using subunit, live attenuated, and genetically engineered approaches. A phase 1/2 trial of a ChAd155-vectored RSV vaccine in infants showed it was being assessed for safety and immunogenicity. However, there is still no licensed RSV vaccine, and safety remains a key concern in ongoing research. ^{7 8 9 10 11}

Is the RSV vaccine for infants and toddlers safe?

There is no currently licensed RSV vaccine, and past attempts have faced safety challenges, including some vaccines causing worse illness. Recent efforts focus on developing safer vaccines, but no definitive safety data is available yet for infants and toddlers. ^{7 8 9 10 11}

Is the RSVt Vaccine a promising treatment for infants and toddlers?

Yes, the RSVt Vaccine is a promising treatment because it aims to protect infants and toddlers from RSV, a virus that can cause serious respiratory illnesses. The vaccine is part of ongoing efforts to develop effective ways to prevent RSV infections, which are a major health concern for young children. ^{7 12 13 14 15}

How is the RSVt Vaccine treatment different from other treatments for RSV in infants and toddlers?

The RSVt Vaccine is unique because it is specifically designed to prevent RSV infections in infants and toddlers, a group for which there are currently no approved vaccines. Unlike previous vaccine attempts that failed due to safety concerns or lack of effectiveness, this vaccine is part of a new generation of candidates focusing on molecular virology to enhance safety and immune response. ^{7 12 13 14 15}

Eligibility Criteria

This trial is for healthy infants and toddlers aged 6 to less than 22 months, born at full term (≥37 weeks). It's designed to test a vaccine against Respiratory Syncytial Virus. Children with certain health conditions or who don't meet the age and birth criteria cannot participate.

Inclusion Criteria

I am between 6 and 22 months old.

Participants who are healthy as determined by medical evaluation including medical history

Born at full term of pregnancy (≥ 37 weeks)

Exclusion Criteria

I live with or could be near someone with a weak immune system.

I have been diagnosed with wheezing by a doctor.

Any acute febrile illness in the past 48 hours that according to investigator judgment is significant enough to interfere with successful inoculation on the day of vaccination. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 intranasal administrations of either the RSVt vaccine or placebo

4 weeks

2 visits (in-person)

Safety Follow-up

Participants are monitored for safety, including solicited and unsolicited adverse events, throughout the study

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• RSVt Vaccine

Trial Overview The study compares an RSV toddler vaccine given through the nose to a placebo in about 6300 young children. Participants are randomly chosen to get either the real vaccine or placebo, and doctors observing won't know which one they got.

Participant Groups

Group I: Group 1 RSVt Vaccine Experimental Treatment 1 Intervention

Participants will receive 2 intranasal administrations of RSVt vaccine

Group II: Group 2 Control Placebo Group 1 Intervention

Participants will receive 2 intranasal administrations of placebo

Who Is Running the Clinical Trial?

Sanofi Pasteur, a Sanofi Company

Lead Sponsor

Trials

429

Recruited

6,140,000+

Paul Hudson

Sanofi Pasteur, a Sanofi Company

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Dr. Thomas Triomphe

Sanofi Pasteur, a Sanofi Company

Chief Medical Officer since 2020

MD from Tehran University of Medical Sciences

Findings from Research

The Gcf A/Bac M2 vaccine candidate successfully induced strong Th1 and CD8+ T-cell responses in mice, leading to effective protective immunity against respiratory syncytial virus (RSV) without causing vaccine-enhanced disease (VED).

This vaccine formulation also resulted in a significant increase in IgG responses compared to Gcf A alone, suggesting that Bac M2 acts as an effective adjuvant, enhancing the immune response to RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine containing G protein fragment and recombinant baculovirus expressing M2 protein induces protective immunity to respiratory syncytial virus. Jo, YM., Kim, J., Chang, J.[2022]

Respiratory syncytial virus (RSV) is a significant cause of illness and death in children, highlighting the urgent need for an effective vaccine.

Recent advancements in molecular technologies have improved the safety of live-attenuated vaccines, and protein-based vaccines are showing promise in clinical trials for both RSV-primed individuals and maternal vaccination to protect infants early in life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory syncytial virus vaccine: Is it coming? Sales, V., Wang, EE.[2021]

Currently, there is no vaccine available for respiratory syncytial virus (RSV), which significantly affects infants and children, but there are 60 vaccine candidates in development, with 16 already in clinical trials.

Challenges remain in balancing safety and immunogenicity for live-attenuated vaccines, and existing treatments like palivizumab are not practical for widespread use in low- and middle-income countries due to cost.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in RSV vaccine research and development - A global agenda. Higgins, D., Trujillo, C., Keech, C.[2022]

A mathematical model suggests that maternal vaccination against RSV at 30 weeks of pregnancy could prevent 62-75% of RSV-related pediatric intensive care unit admissions in the UK and 76-87% in the Netherlands, indicating a significant potential impact on infant health.

The model also predicts that maternal vaccination could reduce RSV-related in-hospital deaths globally by 29-48%, although preterm infants and those with comorbidities may benefit less than healthy term infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential impact of maternal vaccination on life-threatening respiratory syncytial virus infection during infancy. Scheltema, NM., Kavelaars, XM., Thorburn, K., et al.[2018]

Currently, there is no safe and effective vaccine for respiratory syncytial virus (RSV), which poses significant health risks, especially to young children.

The review highlights the need for diverse antiviral treatments and vaccination strategies tailored to different at-risk populations, as existing options are limited and may not adequately address the challenges of RSV infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Up-to-date role of biologics in the management of respiratory syncytial virus. Boyoglu-Barnum, S., Tripp, RA.[2021]

Respiratory syncytial virus (RSV) can cause severe respiratory illness in infants and is also a significant health risk for older adults, highlighting the need for effective prevention strategies.

Despite past failures in developing safe and effective RSV vaccines, current research is focusing on innovative approaches, including subunit vaccines and genetically engineered live attenuated vaccines, to improve immunogenicity and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with respiratory syncytial virus vaccines. Piedra, PA.[2005]

The investigational ChAd155-RSV vaccine was found to have a safety profile similar to other childhood vaccines, with most adverse events occurring at rates comparable to or lower than those of active comparators.

The vaccine induced a strong immune response in infants, with higher RSV neutralizing titers and antibody concentrations compared to the comparator group, and there was no evidence of vaccine-associated enhanced respiratory disease (VAERD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a ChAd155-vectored respiratory syncytial virus vaccine in infants 6-7 months of age: a phase 1/2 randomized trial. Sáez-Llorens, X., Norero, X., Mussi-Pinhata, MM., et al.[2023]

There is currently no safe or effective vaccine for respiratory syncytial virus (RSV), which is a major cause of respiratory infections in infants and the elderly.

Recent advancements in understanding RSV's molecular mechanisms and structural biology have led to renewed efforts in vaccine development, with a diverse pipeline of candidates targeting various populations, making the goal of an effective vaccine more attainable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory syncytial virus vaccine: where are we now and what comes next? Noor, A., Krilov, LR.[2019]

Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in infants, and developing a safe and effective vaccine is challenging due to incomplete immunity from natural infections and the immature immune systems of newborns.

Current promising strategies for RSV vaccination include intranasally delivered genetically engineered vaccines that aim to induce a balanced immune response, as well as maternal vaccination to protect infants from RSV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunopathology of RSV infection: prospects for developing vaccines without this complication. van Drunen Littel-van den Hurk, S., Mapletoft, JW., Arsic, N., et al.[2008]

Palivizumab, a new monoclonal antibody, has been shown to reduce hospitalizations due to respiratory syncytial virus (RSV) by 55% in at-risk infants when given as a preventive treatment during the RSV season.

RSV is a common virus that nearly all children encounter in their first two years, and while treatment options are limited, palivizumab offers a significant protective benefit for vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palivizumab: an overview. Russell, AB.[2019]

The RSV-PreF vaccine demonstrated strong immunogenicity, significantly increasing neutralizing antibody levels against RSV-A and RSV-B in healthy nonpregnant women, with the highest dose (120 µg) showing the greatest antibody response.

The vaccine was well-tolerated with no serious adverse events related to it, indicating a favorable safety profile for future use in pregnant women to potentially protect infants from RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and Safety of 3 Formulations of a Respiratory Syncytial Virus Candidate Vaccine in Nonpregnant Women: A Phase 2, Randomized Trial. Schwarz, TF., McPhee, RA., Launay, O., et al.[2020]

Respiratory Syncytial Virus (RSV) is a significant cause of respiratory illness not only in infants but also in adults, the elderly, and immunocompromised individuals, highlighting the need for effective vaccines across different age groups.

Current prophylactic treatments like RSV-Ig have shown limited success in infants, particularly those with bronchopulmonary dysplasia, and there are safety concerns for its use in infants with congenital heart disease, indicating a need for safer and more effective interventions such as humanized monoclonal antibodies, which are still experimental.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active and passive immunisation against respiratory syncytial virus. Zambon, M.[2019]

Respiratory Syncytial Virus (RSV) is a major cause of severe respiratory illness in infants and vulnerable populations, highlighting the urgent need for effective vaccines.

Current clinical trials are exploring various RSV vaccine candidates across different age groups, including infants, children, pregnant women, and the elderly, aiming to improve prevention strategies against this widespread virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multifaceted approach to RSV vaccination. Blanco, JCG., Boukhvalova, MS., Morrison, TG., et al.[2020]

In a study of 451 participants from rural Kenya, RSV was detected in 84% of households, highlighting the widespread presence of the virus during the 2009-2010 season.

Older school-going siblings were identified as the primary source of RSV infections in infants, accounting for 73% of within-household infections, suggesting that targeting vaccination strategies towards these older children could help protect vulnerable infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The source of respiratory syncytial virus infection in infants: a household cohort study in rural Kenya. Munywoki, PK., Koech, DC., Agoti, CN., et al.[2022]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Vaccine containing G protein fragment and recombinant baculovirus expressing M2 protein induces protective immunity to respiratory syncytial virus. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Respiratory syncytial virus vaccine: Is it coming? [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Advances in RSV vaccine research and development - A global agenda. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Potential impact of maternal vaccination on life-threatening respiratory syncytial virus infection during infancy. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Up-to-date role of biologics in the management of respiratory syncytial virus. [2021]

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

Challenges in developing a pediatric RSV vaccine. [2019]

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

Clinical experience with respiratory syncytial virus vaccines. [2005]

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

Safety and immunogenicity of a ChAd155-vectored respiratory syncytial virus vaccine in infants 6-7 months of age: a phase 1/2 randomized trial. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Respiratory syncytial virus vaccine: where are we now and what comes next? [2019]

10. England pubmed.ncbi.nlm.nih.gov

Immunopathology of RSV infection: prospects for developing vaccines without this complication. [2008]

11. England pubmed.ncbi.nlm.nih.gov

Palivizumab: an overview. [2019]

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

Immunogenicity and Safety of 3 Formulations of a Respiratory Syncytial Virus Candidate Vaccine in Nonpregnant Women: A Phase 2, Randomized Trial. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Active and passive immunisation against respiratory syncytial virus. [2019]

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

A multifaceted approach to RSV vaccination. [2020]

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

The source of respiratory syncytial virus infection in infants: a household cohort study in rural Kenya. [2022]