Safety, Tolerability, and Immunogenicity of VAX-31 in Adults ≥50 Years With Immunobridging to Adults 18-49

A Phase 3, Randomized, Double-Blind, Active-Controlled Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of VAX-31 in Healthy Subjects 50 Years of Age and Older With Immunobridging to Subjects 18-49 Years of Age

The primary objectives of this study are to evaluate the safety, tolerability, immunologic noninferiority (for shared serotypes) and immunologic superiority (for novel serotypes) of VAX-31 compared to PCV21 and PCV20 in adults ≥50 years of age, and to bridge the immune responses induced by VAX-31 in adults 50-64 years of age to adults 18-49 years of age.

Study Overview

• Status: Active, not recruiting
• Conditions: Pneumococcal Vaccines
• Intervention / Treatment: Biological: 31 valent pneumococcal conjugate vaccine; Biological: PCV21; Biological: PCV20

• Study Type: Interventional
• Enrollment (Actual): 4049
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Accel Research Site - Achieve - Birmingham - ERN
  • Arizona
    • Chinle, Arizona, United States, 86503
      • Center for Indigenous Health - Chinle - Johns Hopkins Project
    • Whiteriver, Arizona, United States, 85941
      • Center for Indigineous Health - Whiteriver - John Hopkins Project
  • California
    • Riverside, California, United States, 92506
      • Clinical Innovations Trials - Riverside - CenExel
  • Florida
    • Hollywood, Florida, United States, 33024
      • Research Centers of America - Hollywood - CenExel
    • Jupiter, Florida, United States, 33458
      • Health Awareness - Jupiter - ERN
    • Miami, Florida, United States, 33135
      • Suncoast Research Group LLC
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research - Sunrise
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta - Headlands
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Velocity Clinical Research - Valparaiso (Buynak Clinical Research)
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin-Trials - JCCT
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispecialty Research, LLC - West Wichita
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • DelRicht Clinical Research, LLC - New Orleans
  • Michigan
    • Southfield, Michigan, United States, 48034
      • Headlands Research - Detroit - Headlands
  • Mississippi
    • Gulfport, Mississippi, United States, 39503
      • DelRicht Research, LLC - Gulfport
    • Ridgeland, Mississippi, United States, 39157
      • Sky Integrative Medical Center - SKYCRNG
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Alliance for Multispecialty Research, LLC - Kansas City
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Velocity Clinical Research
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute - CenExe
  • New Mexico
    • Gallup, New Mexico, United States, 87301
      • Center for Indigineous Health - Gallup - John Hopkins Project
    • Shiprock, New Mexico, United States, 87420
      • Center for Indigineous Health - Shiprock - John Hopkins Project
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research - ATLAS - Rochester
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
  • Oklahoma
    • Norman, Oklahoma, United States, 73072
      • Lynn Institute of Norman
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • DM Clinical Research - Philadelphia
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center - Alcanza - HyperCore
  • Texas
    • San Antonio, Texas, United States, 78229
      • Flourish Research - San Antonio
    • Sugar Land, Texas, United States, 77478
      • DM Clinical Research - Sugarland
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical Research - CenExel JBR
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center - Alcanza - HyperCore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female ≥18 years of age (inclusive) at the time of randomization into the study.
• Able and willing to complete the informed consent process.
• Available for clinical follow-up through the last study visit.
• In good general health or with stable underlying chronic condition(s), as determined by medical history, oral temperature, physical examination, and clinical judgment of the Investigator (ongoing chronic conditions must be documented as stable per Investigator).
• Willing to have blood samples collected and used for research purposes.
• Able to provide proof of identity to the satisfaction of the site personnel completing the enrollment process.
• Female participants of childbearing potential, defined as premenopausal females capable of becoming pregnant, must have a negative urine pregnancy test immediately prior to randomization and agree to use acceptable contraception. Male subjects with partners of childbearing potential must agree to practice an acceptable contraception method.
• Able to access and use a device connected to Wi-Fi or cellular network for completion of an electronic diary (eDiary).

Exclusion Criteria:

• History of invasive pneumococcal disease (IPD) or pneumococcal pneumonia (either confirmed or self-reported) at any age.
• Previous receipt of any licensed or investigational pneumococcal vaccine at any age.
• Receipt of any investigational product within 30 days prior to Day 1, currently participating in another interventional investigational study, or having plans to receive another investigational product(s) while on study.
• Receipt of any live vaccine within 30 days prior to Day 1, or receipt of any non-live (including inactivated) vaccine within 14 days prior to Day 1.
• Body temperature >38.0°C (>100.4°F) or acute illness within 3 days prior to study vaccination (subject may be rescreened).
• Current diagnosis of human immunodeficiency virus, Hepatitis B, or Hepatitis C.
• History of severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis to any previous vaccination.
• Individual who is pregnant, breastfeeding, or planning to become pregnant during study participation.
• Has a known or suspected immunocompromising condition, including, but not limited to, leukemia, lymphoma, chronic renal failure, or congenital or acquired immunodeficiency.
• Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) resulting in clinically significant bruising or bleeding difficulties with IM injections or blood draws.
• Receipt of blood or blood product (including polyclonal intravenous immunoglobulin) within 60 days prior to enrollment into the study.
• Is currently receiving immunosuppressive or immune-modifying therapy, including systemic corticosteroids (this includes ≥3 months of prednisone equivalent from 5 to <10 mg/day and ≥2 weeks of prednisone equivalent ≥10 mg/day).
• Received any part of a ≥14-day course of systemic corticosteroids (prednisone equivalent >10 mg/day) within 14 days of study vaccination.
• History of malignancy ≤5 years before enrollment, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Any medical, psychiatric, or social condition that in the judgment of the Investigator is a contraindication to protocol participation or impairs a subject's ability to give informed consent.
• Employee of, or first-degree relative of, any person employed by the Sponsor, the contract research organization (CRO), the Investigator, site personnel, or site.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (VAX-31), participant ≥ 50 years of age; Participants will receive a single dose of VAX-31 administered via intramuscular injection at Day 1	Biological: 31 valent pneumococcal conjugate vaccine; 0.5 mL of VAX-31 will be administered into the deltoid muscle
Active Comparator: Cohort 1 (PCV21), participant ≥ 50 years of age; Participants will receive a single dose of PCV21 (Capvaxive) administered via intramuscular injection at Day 1	Biological: PCV21; 0.5 mL of the 21 valent pneumococcal conjugate vaccine will be administered into the deltoid muscle; Other Names: Capvaxive
Active Comparator: Cohort 1 (PCV20), participant ≥ 50 years of age; Participants will receive a single dose of PCV20 (Prevnar 20) administered via intramuscular injection at Day 1	Biological: PCV20; 0.5 mL of the 20 valent pneumococcal conjugate vaccine will be administered into the deltoid muscle; Other Names: Prevnar 20
Experimental: Cohort 2 (VAX-31), participant 18-49 years of age; Participants will receive a single dose of VAX-31 administered via intramuscular injection at Day 1	Biological: 31 valent pneumococcal conjugate vaccine; 0.5 mL of VAX-31 will be administered into the deltoid muscle
Active Comparator: Cohort 2 (PCV20), participant 18-49 years of age; Participants will receive a single dose of PCV20 (Prevnar 20) administered via intramuscular injection at Day 1	Biological: PCV20; 0.5 mL of the 20 valent pneumococcal conjugate vaccine will be administered into the deltoid muscle; Other Names: Prevnar 20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serotype-specific OPA geometric mean titers (GMT) in 50 year olds and above	1 month after vaccination
Percentage of subjects reporting solicited local adverse events (AE) (redness, swelling, and pain at injection site)	up to 7 days after vaccination
Percentage of subjects reporting solicited systemic AE (fever, headache, fatigue, muscle pain, and joint pain)	up to 7 days after vaccination
Percentage of subjects reporting unsolicited AE	up to 31 days after vaccination
Percentage of subjects reporting serious adverse events (SAE), new onset of chronic illness (NOCI), and medically attended adverse events (MAAE)	up to 6 Months after vaccination
Serotype-specific OPA geometric mean titers (GMT) in 18 to 49 year olds and 50 to 64 year olds	1 month after vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
Serotype-specific IgG geometric mean concentrations (GMC) in 50 year olds and above	1 month after vaccination
Serotype-specific IgG GMC in 18 to 49 year olds and 50 to 64 year olds	1 month after vaccination

Collaborators and Investigators

• Sponsor: Vaxcyte, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 8, 2025
• First Submitted That Met QC Criteria: December 8, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pneumonia; Pneumococcal Infection; 31 Valent PCV
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Pneumonia; Pneumococcal Infections
• Other Study ID Numbers: VAX31-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Vaxcyte is committed to providing access to anonymized data from the company's clinical trials for the purpose of legitimate scientific research. Requests for data may be addressed to datasharing@vaxcyte.com. Requests must be accompanied by a detailed analysis plan and will be reviewed for scientific validity. Data will be made available after initial product approval. Sharing of data may require execution of a data-sharing agreement.
• IPD Sharing Time Frame: Individual participant data will be shared after deidentification and made available starting 6 months after initial product approval.
• IPD Sharing Access Criteria: Criteria will depend on the specific proposal received and may include qualification of the scientific researchers, potential contribution to the research field, scientific rigor of statistical and analytical methods, and other criteria appropriate for the proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No