PCV21 Vaccine for Pneumococcal Infections

Overseen By Clinical Sciences & Operations Study Director & Operations Study Director

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi Pasteur, a Sanofi Company

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

Disqualifiers: Immunodeficiency, Seizures, Neurological 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: Unknown

Duration: 6-11 months

1252 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and immunogenicity of PCV21 versus 20vPCV ( 20-valent pneumococcal conjugate vaccine, Prevnar 20) for catch-up vaccination in infants (7 to 11 MoA-Months of age), toddlers (12 to 23 MoA), and children/adolescents (2 to 5 YoA and 6 to 17 YoA-years of age).

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 receive any vaccines 4 weeks before or after the study vaccine, except for certain flu vaccines. Also, if you are between 2 to 17 years old, you should not have taken antibiotics within 72 hours before the first blood draw.

What data supports the effectiveness of the PCV21 treatment for pneumococcal infections?

Research on similar vaccines, like the 20-valent pneumococcal conjugate vaccine (PCV20), shows that expanding the number of serotypes (variations of the bacteria) covered can increase protection against pneumococcal diseases. This suggests that PCV21, which likely covers even more serotypes, could be effective in preventing these infections. ^{1 2 3 4 5}

Is the PCV21 vaccine safe for humans?

Pneumococcal conjugate vaccines, like PCV7 and PCV9, are generally well tolerated and safe, with mild and self-limited reactions such as local reactions and fever. Some studies noted a possible increased risk of reactive airway disease, but no major safety problems were identified. ^{5 6 7 8 9}

How is the PCV21 vaccine different from other treatments for pneumococcal infections?

The PCV21 vaccine is unique because it is designed to cover more pneumococcal serotypes than existing vaccines, potentially increasing protection, especially in Black older adults who are at higher risk. It aims to improve coverage beyond the current 15- or 20-valent vaccines, addressing more strains of the bacteria that cause pneumococcal infections. ^{3 5 10 11 12}

Eligibility Criteria

This trial is for healthy infants, toddlers, children, and adolescents aged 7 months to 17 years who were born at full term or preterm but stable. Adolescents must agree to use effective contraception or abstain from sexual activity during the study period. Consent forms are required.

Inclusion Criteria

I am of a specific age.

I am considered healthy based on my recent medical exams.

I fit the specific participant and disease requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intramuscular injections of the pneumococcal vaccine according to age group: 1 injection for children/adolescents, 2 injections for toddlers, and 3 injections for infants

6-11 months

Multiple visits for each injection

Follow-up

Participants are monitored for safety and immunogenicity, including serotype-specific IgG concentrations and OPA titers

1 month after last vaccination

Treatment Details

Interventions

• PCV21

Trial Overview The study compares the safety and immune response of a new pneumococcal vaccine (PCV21) with an existing one (20vPCV). It's designed for those who need catch-up vaccinations across different age groups: infants, toddlers, children, and adolescents.

Participant Groups

Group I: Toddlers (12 to 23 MoA) Experimental Treatment 2 Interventions

Participants will receive 2 intramuscular injections of the pneumococcal vaccine with an interval of 8 to 12 weeks (56 to 84 days) between doses

Group II: Infants (7 to 11 MoA) Experimental Treatment 2 Interventions

Participants will receive 3 intramuscular injections of pneumococcal vaccine with an interval of: * 4 to 8 weeks (28 to 56 days) between the 1st dose and the 2nd dose * 8 to 12 weeks (56 to 84 days) between the 2nd dose and the 3rd dose AND age ≥ 12 MoA at 3rd dose

Group III: Children/adolescent (2 to 5 and 6 to 17 YoA) Experimental Treatment 2 Interventions

Participants will receive 1 intramuscular injection of the pneumococcal vaccine

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 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]

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 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) 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]

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]

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]

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]

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 in-development 21-valent pneumococcal vaccine (PCV21) is projected to be more cost-effective and clinically beneficial than the currently recommended 15- or 20-valent vaccines for older adults, particularly for Black older adults who are at higher risk for pneumococcal disease.

In a Markov decision model analysis involving 65-year-old cohorts, PCV21 showed favorable cost-effectiveness ratios of $88,478 per quality-adjusted life-year (QALY) for Black individuals and $127,436/QALY for non-Black individuals, suggesting that PCV21 could justify a future recommendation for broader use in older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of an in-development adult-formulated pneumococcal vaccine in older US adults. Wateska, AR., Nowalk, MP., Lin, CJ., et al.[2023]

References

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

Invasive pneumococcal infections among vaccinated children in the United States. [2015]

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

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

3. 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]

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

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

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

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

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

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

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

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. 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]

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

Effectiveness of the 7-valent pneumococcal conjugate vaccine: a population-based case-control study. [2015]

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

Using the indirect cohort design to estimate the effectiveness of the seven valent pneumococcal conjugate vaccine in England and Wales. [2021]

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

Cost-effectiveness of an in-development adult-formulated pneumococcal vaccine in older US adults. [2023]