Safety, Tolerability, and Immunogenicity of VAX-31 in Adults ≥50 Years With Prior Pneumococcal Vaccination

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 Prior Pneumococcal Vaccination

The study will evaluate the safety, tolerability, and immunogenicity of VAX-31 in adults ≥50 years of age.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 752
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chinle, Arizona, United States, 86503
      • Chinle Center for Indigenous Health
    • Phoenix, Arizona, United States, 85044
      • Avacare (CCT Research)
    • Whiteriver, Arizona, United States, 85941
      • Whiteriver Center for Indigenous Health
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research
  • Florida
    • Hollywood, Florida, United States, 33024
      • CenExel (RCA)
    • Jupiter, Florida, United States, 33458
      • Eximia (Health Awareness)
    • Port Saint Lucie, Florida, United States, 34952
      • Eximia (Health Awareness)
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research
    • The Villages, Florida, United States, 32162
      • The Villages
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • DelRicht Clinical Research
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Velocity Clinical Valparaiso
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin-Trials, LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • DelRicht Clinical Research
  • Maryland
    • Rockville, Maryland, United States, 20854
      • Velocity (Meridian Clinical Research)
  • Michigan
    • Southfield, Michigan, United States, 48076
      • DM Clinical Research-Detroit
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • AMR
    • Springfield, Missouri, United States, 65807
      • DelRicht Research (Command Family Medicine)
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research
  • New Mexico
    • Gallup, New Mexico, United States, 87301
      • Center of American Indian Health
    • Shiprock, New Mexico, United States, 87420
      • Shiprock Center for Indigenous Health
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Carolina
    • Wilmington, North Carolina, United States, 28403
      • Headlands (Trial Management Associates)
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Tekton Research
  • Tennessee
    • Hendersonville, Tennessee, United States, 37075
      • Delricht Research
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research
    • Beaumont, Texas, United States, 77701
      • REX Clinical Trials
    • San Antonio, Texas, United States, 78229
      • Flourish Research
    • Sugar Land, Texas, United States, 77478
      • DM Clinical Research
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Alcanza (Charlottesville Medical Research)
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female ≥50 years of age (inclusive) at the time of randomization into the study.
• Previous receipt of a licensed pneumococcal vaccine or combination of licensed vaccines, with most recent vaccination ≥1 year prior to randomization; the exception is PCV21, which may have been received ≥6 months prior to randomization (confirmed).
• 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:

• Previous invasive pneumococcal disease (IPD) or pneumococcal pneumonia (either confirmed or self-reported) at any age.
• Previous receipt of an 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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (VAX-31): Prior PPSV23; 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 (PCV20): Prior PPSV23; 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
Experimental: Cohort 2 (VAX-31): Prior PCV20; 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): Prior PCV20; 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
Experimental: Cohort 3 (VAX-31): Other prior licensed pneumococcal vaccine or combination; 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 3 (PCV20): Other prior licensed pneumococcal vaccine or combination; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
Serotype-specific OPA geometric mean titers (GMT)	1 month after VAX-31 vaccination
Serotype-specific OPA geometric mean fold rise (GMFR) from baseline	1 month after VAX-31 vaccination
Percentage of subjects reporting new onset of chronic illness (NOCI), medically attended AE (MAAE), and serious adverse events (SAE)	up to 6 months after vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
Serotype-specific IgG geometric mean concentration (GMC)	1 month after VAX-31 vaccination
Serotype-specific IgG geometric mean fold-rise (GMFR) from baseline	1 month after VAX-31 vaccination

Collaborators and Investigators

• Sponsor: Vaxcyte, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 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: VAX31-105

Drug and device information, study documents

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