RSV Vaccine for Infants and Toddlers

(CORAL Trial)

Recruiting at 173 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

Disqualifiers: Immunodeficiency, Chronic illness, Wheezing, 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

Duration: 9 months

2226 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a Phase III, randomized, single-blind, placebo-controlled, multi-center study to be conducted in healthy infants and toddlers which will be enrolled at approximately 6 months of age (Cohort 1) and approximately 12 months of age (Cohort 2). The primary objective of the study will be to assess non-inferiority of the RSV infant and toddler (RSVt) vaccine antibody response when administered concomitantly with routine pediatric vaccines at 6 months of age (Diphtheria and Tetanus Toxoids and Acellular Pertussis, Inactivated Poliovirus, Haemophilus b Conjugate and Hepatitis B Vaccine \[Vaxelis® or Pentacel® and Recombivax HB®\] Prevnar 20®, and RotaTeq®), and 12 months of age (M-M-R II, VARIVAX, and Prevnar 20 or per local country recommendations) compared to when administered non-concomitantly.

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.

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

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like immunosuppressive therapy or systemic corticosteroids may affect eligibility, so it's best to discuss your specific situation with the trial team.

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

The available research shows that while there is no approved RSV vaccine yet, there are promising developments. One study highlights the potential impact of maternal vaccination on reducing life-threatening RSV infections in infants. Another review discusses the progress in developing protein-based vaccines that could provide early life protection. These studies suggest that the RSV vaccine could be effective in preventing serious respiratory illnesses in infants, although more research is needed to confirm its effectiveness. ^{1 2 3 4 5}

What data supports the effectiveness of the RSV vaccine treatment for infants and toddlers?

Research suggests that protein-based RSV vaccines have shown promise in clinical trials for providing early life protection, especially when used in maternal vaccination to protect infants. Additionally, studies have indicated that certain vaccine candidates can induce protective immunity without causing vaccine-enhanced disease, which is a positive sign for their potential effectiveness. ^{1 2 3 4 5}

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

The safety data for RSV vaccines includes several studies and trials. Historically, some early RSV vaccines failed to provide safety and protection, with some causing exaggerated disease upon natural exposure. Recent efforts have focused on developing safer vaccines, such as subunit vaccines, live attenuated vaccines, and genetically engineered vaccines. A Phase 1/2 trial assessed the safety and immunogenicity of a chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV) in infants aged 6-7 months. Another study evaluated the safety of an adenovirus 26 vector RSV vaccine in adults and RSV-seropositive children aged 12-24 months. These studies aim to develop vaccines that elicit a balanced immune response without causing adverse effects. ^{1 6 7 8 9}

Is the RSV vaccine safe for infants and toddlers?

The safety of RSV vaccines has been a focus of research, with some early versions causing issues like exaggerated disease. Recent studies on newer vaccine types, including those tested in infants, are ongoing to ensure they are safe and effective. ^{1 6 7 8 9}

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 serious respiratory illnesses caused by the RSV virus. Recent developments in vaccine technology have led to new and improved vaccine candidates that are in advanced stages of testing. These vaccines are designed to provide better protection and are expected to transform how we prevent RSV infections in young children. ^{6 9 10 11 12}

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

The RSVt vaccine is unique because it is designed to prevent RSV infections in infants and toddlers by stimulating the immune system to recognize and fight the virus, unlike current treatments that mainly focus on managing symptoms. This vaccine aims to provide active immunity, which is different from the passive immunity provided by monoclonal antibodies used for high-risk infants. ^{6 9 10 11 12}

Eligibility Criteria

This trial is for healthy infants and toddlers who are either 6 months + 2 weeks or 12 months ± 2 weeks old, born at full term (≥37 weeks). In the US/Puerto Rico, they must have received specific routine vaccines on schedule before joining. Infants with health issues or not meeting vaccine timelines are excluded.

Inclusion Criteria

Born at full term of pregnancy (≥ 37 weeks)

I am at least 6 months and 2 weeks old for Cohort 1 or 12 months old (plus or minus 2 weeks) for Cohort 2.

Participants who are healthy as determined by medical evaluation including medical history and physical examination

Exclusion Criteria

Known systemic hypersensitivity to study intervention components or history of life-threatening reaction to study intervention

Chronic illness that might interfere with study conduct or completion

I cannot receive certain vaccines due to severe reactions or allergies.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the RSVt vaccine concomitantly or non-concomitantly with routine pediatric vaccines

9 months

Cohort 1: Visits at 6, 7, 8, 9, and 10 months; Cohort 2: Visits at 12, 13, 14, 15, and 16 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• RSVt vaccine

Trial Overview The study tests if the RSVt vaccine's effectiveness is unaffected when given alongside standard childhood vaccines like DTP, IPV, Hib, HepB, rotavirus and pneumococcal conjugate vaccines at ages of approximately 6 and 12 months compared to giving it separately.

Participant Groups

Group I: Cohort 2: Group 4- (RSVt vaccine non-concomitantly at 13 months) Experimental Treatment 5 Interventions

Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 13 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered concomitantly at 12 months of age

Group II: Cohort 2: Group 3- (RSVt vaccine concomitantly at 12 months) Experimental Treatment 5 Interventions

Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 12 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered non-concomitantly at 13 months of age

Group III: Cohort 1: Group 2- (RSVt vaccine non-concomitantly at 7 months) Experimental Treatment 7 Interventions

Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 7 months. Vaccines administered at age 6 months: Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered concomitantly at 6 months of age

Group IV: Cohort 1: Group 1- (RSVt vaccine concomitantly at 6 months) Experimental Treatment 7 Interventions

Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 6 months. Vaccines administered at age 6 months: RSVt Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered non-concomitantly at 7 months of age

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

Approved in United States as Abrysvo for:

• Lower respiratory tract disease (LRTD) caused by RSV in adults aged 60 and older
• LRTD caused by RSV in pregnant women from 32 through 36 weeks gestation to protect newborns up to 6 months old
• LRTD caused by RSV in adults aged 18 through 59 years at higher risk

Approved in United States as Arexvy for:

• Lower respiratory tract disease (LRTD) caused by RSV in adults aged 60 and older
• LRTD caused by RSV in adults aged 50 through 59 years at increased risk

Approved in United States as mRESVIA for:

• Lower respiratory tract disease (LRTD) caused by RSV in adults aged 60 and older

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 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 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 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]

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]

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]

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 Ad26.RSV.preF vaccine candidate showed good safety and immunogenicity in a study involving 12 adults and 36 RSV-seropositive children, with no serious adverse events reported and only mild to moderate reactions observed.

The vaccine significantly increased RSV neutralization titers in children and resulted in fewer RSV infections compared to the placebo group, indicating its potential effectiveness in preventing RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2a Safety and Immunogenicity of an Adenovirus 26 Vector Respiratory Syncytial Virus (RSV) Vaccine Encoding Prefusion F in Adults 18-50 Years and RSV-Seropositive Children 12-24 Months. Stuart, ASV., Virta, M., Williams, K., et al.[2023]

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]

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]

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]

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]

Respiratory syncytial virus (RSV) is a major cause of respiratory illness, particularly in high-risk groups like infants and the elderly, yet there is currently no approved vaccine for prevention.

Early vaccine attempts using inactivated virus led to severe complications in children, highlighting the need for careful development; recent strategies include live attenuated strains and various innovative vaccine technologies, showing cautious progress over the past 40 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory syncytial virus vaccine development. Murata, Y.[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. 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]

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

A multifaceted approach to RSV vaccination. [2020]

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

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

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

Clinical experience with respiratory syncytial virus vaccines. [2005]

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

Phase 1/2a Safety and Immunogenicity of an Adenovirus 26 Vector Respiratory Syncytial Virus (RSV) Vaccine Encoding Prefusion F in Adults 18-50 Years and RSV-Seropositive Children 12-24 Months. [2023]

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

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

10. 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]

11. Canada pubmed.ncbi.nlm.nih.gov

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

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

Respiratory syncytial virus vaccine development. [2021]