Pneumococcal Vaccine for Pneumonia Prevention

Recruiting at 41 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must not be taking: Immunosuppressants, Anticoagulants, Corticosteroids, others

Disqualifiers: Immunodeficiency, Seizures, Bleeding disorders, 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

Compensation: Varies

Number of Visits: 6

Duration: 13 months

2320 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a Phase 3, randomized, modified double-blind study which aims to document the safety profile of the PCV21 vaccine (investigational pneumococcal vaccine) compared to a licensed 20-valent pneumococcal conjugate vaccine in infants aged from approximately 2 months (42 to 89 days). The study duration per participant will be up to approximately 19 months. The study vaccines (either PCV21 or 20vPCV) will be administered at approximately 2, 4, 6 and 12 to 15 months of age. Routine pediatric vaccines will be given as per local recommendations. There will be 6 study visits: Visit (V)01, V02 separated from V01 by 60 days, V03 separated from V02 by 60 days, V04 separated from V03 by 30 days, V05 at 12 months of age until 15 months of age, V06 separated from V05 by 30 days.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications. However, if you are on immunosuppressive therapy, long-term systemic corticosteroids, or have received certain vaccines recently, you may not be eligible to participate.

What data supports the effectiveness of the treatment PCV21 for pneumonia prevention?

Research shows that similar pneumococcal vaccines, like PCV13, have been effective in preventing pneumonia in adults and reducing hospitalizations in children. This suggests that PCV21 might also be effective in preventing pneumonia. ^{1 2 3 4 5}

Is the pneumococcal vaccine generally safe for humans?

Pneumococcal vaccines, including PCV7 and other variants, are generally safe for humans. They may cause mild reactions like local soreness or fever, but serious side effects are rare. Some studies noted a possible link to reactive airway disease, which needs more research. ^{6 7 8 9 10}

How is the PCV21 treatment different from other pneumonia prevention treatments?

PCV21 is unique because it likely builds on the PCV20 vaccine, which covers 20 different strains of the bacteria that cause pneumonia, offering broader protection than previous vaccines like PCV13. This expanded coverage can help protect against more types of pneumococcal infections, potentially reducing the risk of pneumonia more effectively. ^{4 8 11 12 13}

Eligibility Criteria

This trial is for healthy infants aged approximately 2 months (42 to 89 days) at the time of inclusion. They must be deemed healthy by a medical evaluation, which includes their medical history and physical examination.

Inclusion Criteria

I am between 42 and 89 days old today.

I am considered healthy based on my recent medical exams.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 4-dose regimen of either PCV21 or 20vPCV vaccine at approximately 2, 4, 6, and 12 to 15 months of age

13 months

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the last vaccine injection

6 months

Treatment Details

Interventions

• PCV21

Trial Overview The study compares the safety of a new pneumococcal vaccine called PCV21 with an already licensed one, Prevnar 20. Infants will receive vaccines at around 2, 4, 6, and between 12 to15 months old alongside routine pediatric vaccines.

Participant Groups

Group I: Group 1: PCV21 Experimental Treatment 9 Interventions

Participants will be administered via intramuscular injection (IM) a 4-dose PCV21 regimen at approximately 2, 4, 6 and 12 to 15 MoA

Group II: Group 2: 20vPCV Active Control 9 Interventions

Participants will be administered via intramuscular injection (IM) a 4-dose 20vPCV regimen at approximately 2, 4, 6 and 12 to 15 MoA

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

The 13-valent pneumococcal conjugate vaccine (PCV13) showed an overall vaccine effectiveness (VE) of 33.2% against pneumococcal community-acquired pneumonia (pCAP) in adults aged 65 and older, indicating some level of protection despite modest vaccine uptake.

In a subgroup of patients managed in the community, the VE was significantly higher at 88.1% against any pneumococcal strain, suggesting that PCV13 could be particularly effective in community settings, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of the 13-valent pneumococcal conjugate vaccine against adult pneumonia in Italy: a case-control study in a 2-year prospective cohort. Prato, R., Fortunato, F., Cappelli, MG., et al.[2019]

In a study involving 194 hospitalized children with influenza and 342 matched controls, the pneumococcal conjugate vaccine (PCV) significantly reduced hospitalizations by 48% during the 2009-2010 pandemic wave for fully vaccinated children under 5 years old.

However, during the 2010-2011 influenza season, the study found no significant benefit of PCV vaccination in preventing hospitalizations, indicating that the effectiveness of the vaccine may vary by season.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit of conjugate pneumococcal vaccination in preventing influenza hospitalization in children: a case-control study. Domínguez, A., Castilla, J., Godoy, P., et al.[2013]

A study of 1,365,893 children in Australia found that pneumococcal conjugate vaccines (PCVs) significantly reduced hospital admissions for pneumonia, particularly among Aboriginal children, who experienced a 49% reduction in admissions after full vaccination.

While both vaccinated and unvaccinated non-Aboriginal children showed decreased pneumonia admissions, the most substantial benefits of PCV were observed in Aboriginal children, highlighting the importance of vaccination in high-incidence populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of pneumococcal conjugate vaccine against hospital admissions for pneumonia in Australian children: a retrospective, population-based, record-linked cohort study. Fathima, P., Gidding, HF., McIntyre, PB., et al.[2021]

The 20-valent pneumococcal conjugate vaccine (PCV20) significantly reduces the incidence and mortality of pneumococcal diseases in Danish adults compared to the 23-valent pneumococcal polysaccharide vaccine (PPV23), leading to substantial health benefits.

Vaccination with PCV20 is a cost-effective strategy, potentially saving up to 396 million EUR while gaining thousands of quality-adjusted life years (QALYs), making it a dominant choice for adults at moderate or high risk and those aged 65 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in Denmark compared with PPV23. Olsen, J., Schnack, H., Skovdal, M., et al.[2022]

The introduction of the seven-valent pneumococcal vaccine has led to significant declines in invasive pneumococcal disease and antibiotic-resistant infections in children, demonstrating its efficacy and safety.

Newer pneumococcal conjugate vaccines (PHiD-CV and PCV-13) are being developed to provide broader coverage, particularly in developing countries, while ongoing research is exploring alternative vaccine strategies based on pneumococcal proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pneumococcal conjugated vaccines: impact of PCV-7 and new achievements in the postvaccine era. Dinleyici, EC., Yargic, ZA.[2008]

Pneumococcal conjugate vaccines (PCV7 and PCV9) are highly immunogenic and effective, with PCV7 showing 82-97% efficacy against invasive pneumococcal disease and 90% against pneumococcal pneumonia, based on various randomized controlled trials.

PCVs are generally safe and well-tolerated, even when given alongside other childhood vaccines, and studies suggest that fewer doses (2+1 schedule) can achieve similar protective immunity as the standard 3+1 schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity, efficacy, safety and effectiveness of pneumococcal conjugate vaccines (1998-2006). Oosterhuis-Kafeja, F., Beutels, P., Van Damme, P.[2022]

The 20-valent pneumococcal conjugate vaccine (PCV20) was found to be safe and well tolerated, with no significant safety concerns reported in a phase 3 study involving adults across three age groups (18-49, 50-59, and ≥60 years).

PCV20 demonstrated comparable immunogenicity to the 13-valent PCV (PCV13) and the 23-valent polysaccharide vaccine (PPSV23), effectively inducing immune responses to all 20 vaccine serotypes, which suggests it could provide broader protection against pneumococcal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pivotal Phase 3 Randomized Clinical Trial of the Safety, Tolerability, and Immunogenicity of 20-Valent Pneumococcal Conjugate Vaccine in Adults Aged ≥18 Years. Essink, B., Sabharwal, C., Cannon, K., et al.[2022]

The Heptavalent pneumococcal conjugate vaccine (PCV-7) is currently the only approved vaccine for preventing invasive pneumococcal disease in children under two years old, demonstrating good safety when given alone or with other vaccines.

PCV-7 has been shown to be safe and effective in infants with HIV and those with sickle cell disease, highlighting its broad applicability in vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of 7-valent pneumococcal conjugate vaccine. Ghaffar, F.[2007]

A systematic review of 42 studies found that the 7-valent pneumococcal conjugate vaccine (PCV7) is generally safe, with mild and self-limited local reactions and fever, but no increased risk of severe side effects.

While some studies indicated a potential link between pneumococcal vaccines and an increased risk of hospitalization for reactive airway disease, the overall safety profile of PCV7 remains favorable, warranting further investigation into this specific concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of pneumococcal conjugate vaccines: systematic review of pre- and post-licensure data. Destefano, F., Pfeifer, D., Nohynek, H.[2021]

A study analyzing data from Finnish population registers found no significant increase in adverse events after the introduction of the ten-valent Pneumococcal Conjugate Vaccine (PCV10) in children, except for a higher incidence of urticarial rash, which was attributed to changes in healthcare coding rather than the vaccine itself.

The findings suggest that public health concerns regarding adverse events linked to PCV10 are unfounded, highlighting the effectiveness of using real-world data for validating safety signals in vaccination programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Register-Based Ecologic Evaluation of Safety Signals Related to Pneumococcal Conjugate Vaccine in Children. Artama, M., Rinta-Kokko, H., Nohynek, H., et al.[2018]

The protein-conjugate pneumococcal vaccine (PCV) offers strong protection against pneumococcal disease in children, but its effectiveness may be reduced by the emergence of new replacement strains.

Current evidence suggests that PCV is at least as effective as the pneumococcal polysaccharide vaccine (PPV) in adults, but those most in need of vaccination often have a weaker response, raising concerns about the cost-effectiveness of widespread PCV use in adult populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role for protein-conjugate pneumococcal vaccine in adults: what is the supporting evidence? Musher, DM., Sampath, R., Rodriguez-Barradas, MC.[2022]

The 20-valent pneumococcal conjugate vaccine (PCV20) was found to be safe and well-tolerated in adults aged 65 and older, with similar rates of local reactions and adverse events compared to the control groups (PCV13 and PPSV23).

PCV20 elicited strong immune responses against all 20 serotypes included in the vaccine, demonstrating its effectiveness in boosting immunity regardless of prior pneumococcal vaccination history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in populations of adults ≥65 years of age with different prior pneumococcal vaccination. Cannon, K., Elder, C., Young, M., et al.[2022]

The 20-valent pneumococcal conjugate vaccine (PCV20) has been approved for use in adults since June 2021 and in pediatric populations since April 2023, targeting a broader range of Streptococcus pneumoniae serotypes compared to the previous 13-valent vaccine.

PCV20 is effective in preventing invasive pneumococcal disease and otitis media in children aged 6 weeks to 17 years, demonstrating its safety and immunogenicity in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

20‑Valent Pneumococcal Conjugate Vaccine: Pediatric First Approval. Shirley, M.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Effectiveness of the 13-valent pneumococcal conjugate vaccine against adult pneumonia in Italy: a case-control study in a 2-year prospective cohort. [2019]

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

Benefit of conjugate pneumococcal vaccination in preventing influenza hospitalization in children: a case-control study. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Effectiveness of pneumococcal conjugate vaccine against hospital admissions for pneumonia in Australian children: a retrospective, population-based, record-linked cohort study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in Denmark compared with PPV23. [2022]

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

Pneumococcal conjugated vaccines: impact of PCV-7 and new achievements in the postvaccine era. [2008]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Immunogenicity, efficacy, safety and effectiveness of pneumococcal conjugate vaccines (1998-2006). [2022]

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

Pivotal Phase 3 Randomized Clinical Trial of the Safety, Tolerability, and Immunogenicity of 20-Valent Pneumococcal Conjugate Vaccine in Adults Aged ≥18 Years. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The safety of 7-valent pneumococcal conjugate vaccine. [2007]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety profile of pneumococcal conjugate vaccines: systematic review of pre- and post-licensure data. [2021]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Register-Based Ecologic Evaluation of Safety Signals Related to Pneumococcal Conjugate Vaccine in Children. [2018]

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

The potential role for protein-conjugate pneumococcal vaccine in adults: what is the supporting evidence? [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

A trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in populations of adults ≥65 years of age with different prior pneumococcal vaccination. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

20‑Valent Pneumococcal Conjugate Vaccine: Pediatric First Approval. [2023]