Safety, Tolerability, and Immunogenicity of a 24-Valent Pneumococcal Conjugate Vaccine (VAX-24) in Healthy Infants

• ClinicalTrials.gov Identifier: NCT05844423
• Recruitment Status: Active, not recruiting
• First Posted: May 6, 2023
• Last Update Posted: March 12, 2024
• Sponsor: Vaxcyte, Inc.
• Information provided by (Responsible Party): Vaxcyte, Inc.

Tracking Information

• First Submitted Date: April 24, 2023
• First Posted Date: May 6, 2023
• Last Update Posted Date: March 12, 2024
• Actual Study Start Date: March 29, 2023
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2023)

• Percentage of participants with any solicited local injection site Adverse Events (AE) within 7 days after each vaccination [ Time Frame: 7 days after each vaccination ]
  Solicited local reactions include erythema, edema, and tenderness at the injection site
• Percentage of participants with any solicited systemic AE within 7 days after each vaccination [ Time Frame: 7 days after each vaccination ]
  Solicited systemic reactions include fever, irritability, decreased appetite, decreased sleep, and increased sleep
• Percentage of participants with any related Serious Adverse Events (SAE) within 6 months after last vaccination [ Time Frame: 6 months after last vaccination ]
  Percentage of participants with related SAE

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 24, 2023)

• Percentage of subjects with any unsolicited AE within 1 month after each vaccination [ Time Frame: 1 month after each vaccination ]
  Percentage of subjects with any unsolicited AE
• Percentage of subjects with any unsolicited AE from Dose 1 through 1 month post-Dose 3 [ Time Frame: First vaccination (Dose 1) through 1 month after third vaccination (Dose 3) ]
  Percentage of subjects with any unsolicited AE between first and 3rd vaccination in the primary series
• Percentage of subjects with any AE resulting in discontinuation of study within 6 months after last vaccination [ Time Frame: 6 months after last vaccination ]
  Percentage of subjects with any AE resulting in discontinuation of study
• Percentage of subjects with any new onset of chronic illness (NOCI) within 6 months after last vaccination [ Time Frame: 6 months after last vaccination ]
  Percentage of subjects with any NOCI
• Percentage of subjects with any medically attended adverse events (MAAE) within 6 months after last vaccination [ Time Frame: 6 months after last vaccination ]
  Percentage of subjects with any MAAE
• Percentage of subjects with any SAE within 6 months after last vaccination [ Time Frame: 6 months after last vaccination ]
  Percentage of subjects with any SAE
• Percentage of subjects achieving an anti-pneumococcal Immunoglobulin G (IgG) antibody concentration ≥0.35 mcg/mL 1 month after Dose 3 [ Time Frame: 1 month after Dose 3 ]
  Percentage of subjects achieving an anti-pneumococcal IgG antibody concentration ≥0.35 mcg/mL
• Percentage of subjects achieving an anti-pneumococcal IgG antibody concentration ≥0.35 mcg/mL 1 month after Dose 4 [ Time Frame: 1 month after Dose 4 ]
  Percentage of subjects achieving an anti-pneumococcal IgG antibody concentration ≥0.35 mcg/mL
• IgG antibody Geometric Mean Concentration (GMC) 1 month after Dose 3 [ Time Frame: 1 month after Dose 3 ]
  Antibody geometric mean concentrations as measured by IgG for the 24 pneumococcal serotypes in VAX-24
• IgG antibody GMC 1 month after Dose 4 [ Time Frame: 1 month after Dose 4 ]
  Antibody geometric mean concentrations as measured by IgG for the 24 pneumococcal serotypes in VAX-24
• Opsonophagocytic activity (OPA) Geometric Mean Titer (GMT) 1 month after Dose 3 [ Time Frame: 1 month after Dose 3 ]
  Antibody geometric mean titers s as measured by OPA for the 24 pneumococcal serotypes in VAX-24
• OPA GMT 1 month after Dose 4 [ Time Frame: 1 month after Dose 4 ]
  Antibody geometric mean titers s as measured by OPA for the 24 pneumococcal serotypes in VAX-24
• IgG Geometric Mean Fold Ratio (GMFR) before Dose 4 to 1 month after Dose 4 [ Time Frame: Pre-Dose 4 to 1 month after Dose 4 ]
  Antibody geometric mean fold ratio as measured by IgG for the 24 pneumococcal serotypes in VAX-24
• OPA GMFR before Dose 4 to 1 month after Dose 4 [ Time Frame: Pre-Dose 4 to 1 month after Dose 4 ]
  Antibody geometric mean fold rise as measured by OPA for the 24 pneumococcal serotypes in VAX-24
• Percentage of subjects achieving at least a 4-fold increase in IgG from pre-Dose 4 to 1 month post Dose 4 [ Time Frame: Pre-Dose 4 to 1 month after Dose 4 ]
  Geometric mean concentration with a at least a 4-fold increase in IgG antibodies for the 24 pneumococcal serotypes in VAX-24
• Percentage of subjects achieving at least a 4-fold increase in OPA titers from pre-Dose 4 to 1 month post Dose 4 [ Time Frame: Pre-Dose 4 to 1 month after Dose 4 ]
  Geometric mean titer with a at least a 4-fold increase in OPA titers for the 24 pneumococcal serotypes in VAX-24

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, and Immunogenicity of a 24-Valent Pneumococcal Conjugate Vaccine (VAX-24) in Healthy Infants
• Official Title: Randomized, Observer-Blind, Active-Controlled, Dose-Finding Study to Evaluate the Safety, Tolerability, and Immunogenicity of 24-Valent PCV (VAX-24) in Infants Given 4 Doses at 2, 4, 6, and 12-15 Months of Age With Pediatric Vaccines
• Brief Summary: The objective of the study is to evaluate the safety and tolerability of 4 injections of VAX-24 (at 3 dose levels) compared to PCV15 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose: Prevention

• Condition: Pneumococcal Vaccines

Intervention

• Biological: 0.5 ml dose of 1.1 mcg VAX-24
  24 valent pneumococcal conjugate vaccine
• Biological: 0.5 ml dose of PCV20
  20 valent pneumococcal conjugate vaccine
• Biological: 0.5 ml dose of 2.2 mcg VAX-24
  24 valent pneumococcal conjugate vaccine
• Biological: 0.5 ml dose of 2.2/4.4 mcg VAX-24
  24 valent pneumococcal conjugate vaccine

Study Arms

• Experimental: VAX-24 Low
  Participants will receive 4 doses of VAX-24 administered as an intramuscular injection at 2, 4, 6, and 12-15 months of age at one of three dose levels.
  Intervention: Biological: 0.5 ml dose of 1.1 mcg VAX-24
• Experimental: VAX-24 Mid
  Participants will receive 4 doses of VAX-24 administered as an intramuscular injection at 2, 4, 6, and 12-15 months of age at one of three dose levels.
  Intervention: Biological: 0.5 ml dose of 2.2 mcg VAX-24
• Experimental: VAX-24 Mixed
  Participants will receive 4 doses of VAX-24 administered as an intramuscular injection at 2, 4, 6, and 12-15 months of age at one of three dose levels.
  Intervention: Biological: 0.5 ml dose of 2.2/4.4 mcg VAX-24
• Active Comparator: PCV20
  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.
  Intervention: Biological: 0.5 ml dose of PCV20

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 9, 2024): 802
• Original Estimated Enrollment (submitted: April 24, 2023): 800
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Healthy male or female infant ≥42 days to ≤89 days (inclusive).
2. Full-term infant at least 37 weeks gestational age at birth.
3. Afebrile for ≥72 hours with a rectal temperature <38.0°C (<100.4°F) or axillary temperature <37.8°C (<100.0°F) before receipt of study vaccine.*
4. Able to attend all scheduled visits and comply with the study procedures.
5. Subject's parent/legal guardian is able to read and understands the study procedures, alternate treatments, risks and benefits, and provides written informed consent.
6. Subject's parent/legal guardian is able to fill out an ediary of solicited AE and take daily axillary temperature and measurements of local injection site reactions for the 7 days after each study vaccination.
7. Subject's parent/legal guardian has an e-mail address and access to a computer or smartphone with internet to complete the ediary.

Exclusion Criteria:

1. History of invasive pneumococcal disease (positive blood culture, positive cerebrospinal fluid culture, or other sterile site) or known history of other culture positive pneumococcal disease.
2. Previous receipt of a licensed or investigational vaccine (excluding 1 dose hepatitis B vaccine).
3. Known hypersensitivity to any vaccine.
4. Known or suspected impairment of immunological function (e.g., asplenia, HIV, primary immunodeficiency).
5. Use of any immunosuppressive therapy (Note: topical and inhaled/nebulized steroids are permitted).
6. History of failure to thrive.
7. Subject has a coagulation disorder contraindicating IM vaccination.
8. Subject or his/her mother have documented hepatitis B surface antigen-positive.
9. Has a known neurologic or cognitive behavioral disorder.
10. Has a known clinically significant congenital malformation or serious chronic disorder.
11. Receipt of a blood transfusion or blood products, including immunoglobulins.
12. Receipt of any investigational study product since birth, currently participating in another interventional investigational study, or having plans to receive another investigational product(s) while on study.
13. Any infant who cannot be adequately followed for safety according to the protocol plan.
14. Any other reason that in the opinion of the investigator may interfere with the evaluation required by the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 42 Days to 89 Days (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05844423
• Other Study ID Numbers: VAX24-112
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Vaxcyte, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Vaxcyte, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Vaxcyte, Inc.
• Verification Date: March 2024