VAX-31 Vaccine for Pneumococcal Prevention

Recruiting at 46 trial locations

Overseen By Clinical Development

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Vaxcyte, Inc.

Must not be taking: Immunosuppressants

Disqualifiers: Pneumococcal disease, Immunodeficiency, Bleeding disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 4

Duration: 13 months

800 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of the study is to evaluate the safety, tolerability, and immunogenicity of 4 injections of VAX-31 (at 3 dose levels) compared to PCV20 in infants at 2, 4, 6, and 12-15 months of age, in addition to receiving routine US concomitant vaccines. Stage 1 of the study will comprise 3 dose ascending cohorts. Stage 2 of the study will enroll the remainder of the sample size.

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, if you are using immunosuppressive therapy, you may need to stop, as its use is not allowed during the trial.

What data supports the effectiveness of the VAX-31 treatment for pneumococcal prevention?

Research on similar vaccines, like the 7-valent and 11-valent pneumococcal conjugate vaccines, shows they are effective in preventing invasive pneumococcal diseases, especially in children. These vaccines have been shown to reduce disease rates and even decrease antibiotic resistance, suggesting that a 31-valent vaccine like VAX-31 could potentially offer broader protection. ^{1 2 3 4 5}

Is the VAX-31 vaccine safe for humans?

Pneumococcal conjugate vaccines, like the 13-valent version, have been shown to be generally safe in infants, with most reactions being mild or moderate, similar to other vaccines. These vaccines are well tolerated and have a good safety profile when used in children. ^{6 7 8 9 10}

How is the VAX-31 vaccine different from other pneumococcal vaccines?

The VAX-31 vaccine is unique because it is a 31-valent pneumococcal conjugate vaccine, meaning it targets 31 different strains of the pneumococcal bacteria, potentially offering broader protection compared to existing vaccines like the 7-valent or 13-valent versions, which target fewer strains. ^{1 11 12 13 14}

Eligibility Criteria

This trial is for healthy infants who are scheduled to receive routine vaccinations. It's designed to test a new pneumococcal vaccine called VAX-31 at different doses compared with an existing vaccine, PCV20.

Inclusion Criteria

My baby was born full-term, at 37 weeks or later.

Subject's parent/legal guardian is able to read and understand the study procedures, alternate treatments, risks and benefits, and provides written informed consent

My infant is between 42 and 89 days old.

Exclusion Criteria

I have had a serious pneumococcal infection confirmed by testing.

Receipt of any investigational study product since birth, currently participating in another interventional investigational study, or plans to receive another investigational product while on study

I have received a blood transfusion or blood products.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 doses of VAX-31 or PCV20 at 2, 4, 6, and 12-15 months of age

13 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• VAX-31

Trial Overview The study tests the safety and immune response of three different doses of VAX-31 against PCV20 in infants during their regular vaccination schedule at 2, 4, 6, and 12-15 months old. The trial has two stages: initial dose-level testing followed by full enrollment.

Participant Groups

Group I: VAX-31 Mid Experimental Treatment 1 Intervention

Participants will receive 4 doses of VAX-31 administered as an intramuscular injection at 2, 4, 6, and 12-15 months of age at one of three dose levels.

Group II: VAX-31 Low Experimental Treatment 1 Intervention

Participants will receive 4 doses of VAX-31 administered as an intramuscular injection at 2, 4, 6, and 12-15 months of age at one of three dose levels.

Group III: VAX-31 High Experimental Treatment 1 Intervention

Participants will receive 4 doses of VAX-31 administered as an intramuscular injection at 2, 4, 6, and 12-15 months of age at one of three dose levels.

Group IV: PCV20 Active Control 1 Intervention

Participants will receive 4 doses of PCV20 administered as an intramuscular injection of the standard dose at 2, 4, 6, and 12-15 months of age.

VAX-31 is already approved in United States for the following indications:

Approved in United States as VAX-31 for:

• Prevention of invasive pneumococcal disease (IPD) in infants and adults

Who Is Running the Clinical Trial?

Vaxcyte, Inc.

Lead Sponsor

Trials

5

Recruited

3,700+

Findings from Research

The 11-valent pneumococcal conjugate vaccine (11-PncTD) was found to be safe and well-tolerated in a study of 50 infants, with local reactions similar to those from the standard DTwP//PRP-T vaccine.

The vaccine elicited strong antibody responses against most pneumococcal serotypes, indicating good immunogenicity, although it was less effective for serotype 14, which had a high pre-vaccination antibody level.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of three doses of an eleven-valent diphtheria toxoid and tetanus protein--conjugated pneumococcal vaccine in Filipino infants. Capeding, MZ., Puumalainen, T., Gepanayao, CP., et al.[2018]

In a study involving 523 cases of invasive pneumococcal disease (IPD) in children, both the 13-valent pneumococcal conjugate vaccine (PCV13) and a combination of 7-valent (PCV7) and 10-valent (PCV10) vaccines showed similar effectiveness against all-serotype IPD, with effectiveness rates of 76% and 78%, respectively.

PCV13 demonstrated a high effectiveness of 82% against serotype 19A IPD, while the combined PCV7/PCV10 plus PCV13 showed even higher effectiveness at 87%, indicating that the choice of vaccine can significantly impact protection against specific serotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Pneumococcal Conjugate Vaccines of Different Valences Against Invasive Pneumococcal Disease Among Children in Taiwan: A Nationwide Study. Su, WJ., Lo, HY., Chang, CH., et al.[2019]

The 13-valent pneumococcal conjugate vaccine (13vPnC) was found to be immunogenic in healthy Japanese adults, showing adequate antibody responses for most serotypes, which supports its potential use in children and older adults.

While there was a trend towards more local reactions with the 13vPnC compared to the 23-valent polysaccharide vaccine (23vPn), these reactions were mostly mild or moderate, indicating that the vaccine is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of 13-valent pneumococcal conjugate vaccine in Japanese adults. Scott, D., Ruckle, J., Dar, M., et al.[2016]

The seven-valent conjugate pneumococcal vaccine is highly effective against invasive pneumococcal disease and is recommended for routine use in infants and high-risk children in the U.S., highlighting its importance in preventing serious infections.

While the vaccine shows effectiveness, there is a concern about serotype replacement, which could diminish its overall effectiveness, and it may also help reduce antimicrobial resistance in pneumococci.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conjugate pneumococcal vaccines: an overview. Mulholland, EK.[2020]

The 7-valent conjugate pneumococcal vaccine effectively prevents 75-90% of invasive pneumococcal disease cases in children, depending on the distribution of vaccine serotypes in different countries.

Recent studies in North America indicate that mass vaccination campaigns not only protect vaccinated children but also reduce the spread of antibiotic-resistant vaccine serotypes in the community, suggesting broader public health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[7-valent conjugate Pneumococcal vaccine and nasopharyngeal cavity]. Piffer, S.[2015]

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 13-valent pneumococcal conjugate vaccine is shown to be as safe and effective as the 7-valent vaccine in infants, with both vaccines well tolerated and most reactions being mild or moderate.

The 13-valent vaccine not only protects against the seven common serotypes but also offers expanded protection against six additional serotypes, achieving high immunogenicity with at least 89% of infants reaching protective antibody levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine in infants: a meta-analysis. Ruiz-Aragón, J., Márquez Peláez, S., Molina-Linde, JM., et al.[2015]

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 pneumococcal 7-valent conjugate vaccine has been shown to be highly effective, safe, and immunogenic in infants, who are particularly vulnerable to serious pneumococcal diseases.

Given the rise of drug-resistant strains of S. pneumoniae, this vaccine is crucial for preventing infections like pneumonia and meningitis, with ongoing trials assessing its efficacy against these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pneumococcal disease in United States children: prevalence and treatment. Clanton, M.[2005]

The pneumococcal seven valent conjugate vaccine (PCV-7) significantly reduces invasive pneumococcal disease and nasopharyngeal colonization, but its impact on acute otitis media (AOM) rates is minimal, especially in children under 24 months.

Despite the ongoing shortage of PCV-7 leading to fewer doses being administered, the incidence of invasive pneumococcal disease continues to decline, indicating that other factors, such as herd immunity, may also play a role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in treatment strategies for acute otitis media after full implementation of the pneumococcal seven valent conjugate vaccine. Harrison, CJ.[2019]

Children who received 3 or more doses of the 7-valent pneumococcal conjugate vaccine (PCV7) by 12 months of age had a significantly lower risk of acute otitis media (AOM) and lower respiratory tract infections (LRTIs) compared to nonimmunized children, with relative risks of 0.86 and 0.78, respectively.

The study found that PCV7 immunization continued to show reduced risks of AOM and LRTIs between 18 and 36 months of age, but there was no link between PCV7 immunization and asthma at 36 months, indicating its specific protective effects against certain infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decline in early childhood respiratory tract infections in the Norwegian mother and child cohort study after introduction of pneumococcal conjugate vaccination. Magnus, MC., Vestrheim, DF., Nystad, W., et al.[2021]

The 13-Valent pneumococcal conjugate vaccine (PCV13) is as effective as the 7-Valent vaccine (PCV7) in generating immune responses against the common serotypes of pneumococcal disease, while also providing additional protection against 6 extra serotypes.

Both vaccines have similar safety profiles, with PCV13 showing mild reactogenicity, indicating it is a safe option for infants receiving routine vaccinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in infants and toddlers. Yeh, SH., Gurtman, A., Hurley, DC., et al.[2015]

The heptavalent conjugated pneumococcal vaccine (PCV7) is highly immunogenic and significantly reduces the incidence of invasive pneumococcal disease in children, with reductions of 87% in those under 1 year old after routine vaccination.

While PCV7 is effective in preventing certain types of invasive pneumococcal diseases, its overall impact on acute otitis media is limited, and its cost-effectiveness is questionable after four doses, particularly for children over 4 years old.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conjugated heptavalent pneumococcal vaccine. Pai, VB., Heyneman, CA., Erramouspe, J.[2017]

The 13-valent pneumococcal conjugate vaccine (PCV13) was found to be as effective as the 7-valent vaccine (PCV7) in generating immune responses to the 7 common pneumococcal serotypes in healthy Japanese infants, while also providing significantly higher responses to 6 additional serotypes.

The combination of PCV13 with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP) was shown to be safe and well tolerated, with comparable immune responses to DTaP antigens across all groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and Safety of a 13-Valent Pneumococcal Conjugate Vaccine Given With DTaP Vaccine in Healthy Infants in Japan. Togashi, T., Okada, K., Yamaji, M., et al.[2018]

References

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

Safety and immunogenicity of three doses of an eleven-valent diphtheria toxoid and tetanus protein--conjugated pneumococcal vaccine in Filipino infants. [2018]

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

Effectiveness of Pneumococcal Conjugate Vaccines of Different Valences Against Invasive Pneumococcal Disease Among Children in Taiwan: A Nationwide Study. [2019]

3. Australia pubmed.ncbi.nlm.nih.gov

Phase 1 trial of 13-valent pneumococcal conjugate vaccine in Japanese adults. [2016]

4. Australia pubmed.ncbi.nlm.nih.gov

Conjugate pneumococcal vaccines: an overview. [2020]

5. Italy pubmed.ncbi.nlm.nih.gov

[7-valent conjugate Pneumococcal vaccine and nasopharyngeal cavity]. [2015]

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

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine in infants: a meta-analysis. [2015]

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

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

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

Pneumococcal disease in United States children: prevalence and treatment. [2005]

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

Changes in treatment strategies for acute otitis media after full implementation of the pneumococcal seven valent conjugate vaccine. [2019]

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

Decline in early childhood respiratory tract infections in the Norwegian mother and child cohort study after introduction of pneumococcal conjugate vaccination. [2021]

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

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in infants and toddlers. [2015]

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

Conjugated heptavalent pneumococcal vaccine. [2017]

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

Immunogenicity and Safety of a 13-Valent Pneumococcal Conjugate Vaccine Given With DTaP Vaccine in Healthy Infants in Japan. [2018]