A Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of VAX-A1 in Healthy Young Adults

A Phase 1, First-in-Human, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Immunogenicity of VAX-A1 in Healthy Young Adults

This is a phase 1, first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, and immunogenicity of VAX-A1 in healthy adults 18-40 years of age.

Study Overview

• Status: Not yet recruiting
• Conditions: Group A Streptococcal Infection
• Intervention / Treatment: Biological: VAX-A1 Low; Biological: VAX-A1 Mid; Biological: VAX-A1 High; Biological: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Development; Phone Number: 650-837-0111; Email: Clinicaltrialsgov@vaxcyte.com

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5067
      • Fusion Clinical Research
      • Contact: Christopher D Rook, MD; Phone Number: +61 8 7088 7900; Email: christopher.rook@cmax.com.au
      • Principal Investigator: Christopher Rook, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Individuals 18-40 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 at 6 months post-Dose 2
• Willing to have blood samples collected, stored indefinitely, and be used for research purposes
• Able to provide proof of identity to the satisfaction of the study staff completing the enrollment process
• Healthy, as defined by absence of clinically significant medical condition, either acute or chronic, as determined by medical history, vital signs, physical examination, screening laboratory test results, TTE and ECG results, and clinical assessment by the Investigator
• For applicable individuals, postmenopausal (as confirmed by follicle-stimulating hormone [FSH] level at Screening) for at least 1 year, or surgically sterile for at least 6 months prior to dosing
• Individuals of childbearing potential must be not pregnant and not lactating, must have negative urine and serum pregnancy tests at Screening and a negative urine pregnancy test immediately prior to randomization, and agree to use acceptable contraception if heterosexually active. Participants must agree to consistently practice contraception if sexually active at least 7 days prior to enrollment and throughout the duration of the study
• Able to access and use a smartphone, tablet, computer, or other device connected to Wi-Fi or cellular network for completion of an eDiary

Exclusion Criteria:

• History of any clinically important cardiac, rheumatologic, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other disease as determined by the Investigator. This includes a history of polyarthritis, nephropathy, pericarditis, myocarditis, or hypertension requiring current pharmacologic treatment.
• History of invasive GAS infection (such as toxic shock syndrome, necrotizing fasciitis, bloodstream infection, pleural empyema, meningitis) or poststreptococcal immune mediated disease (such as RHD, ARF, or APSGN)
• Known or suspected autoimmune disease, collagen vascular disease, or impairment/alteration of immune function (e.g., congenital or acquired immunodeficiency)
• Previous or existing diagnosis of human immunodeficiency virus, Hepatitis B virus, or Hepatitis C virus, or a positive serologic test at Screening
• History of malignancy or neoplasm, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
• Bleeding disorder diagnosed by a physician (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
• History of severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis to any previous vaccination
• Oral temperature >38.0°C (>100.4°F) or acute illness within 3 days prior to study vaccination (subject may be rescreened)
• Confirmed elevated BP at Screening, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg measured seated after ≥5 minutes rest and confirmed by repeat measurement
• Physical examination indicating any clinically significant medical condition or inadequate venous access
• Any Grade ≥2 abnormal safety laboratory test at Screening
• Abnormal ESR, or CRP or C3 levels at Screening
• Confirmed microscopic hematuria (>10 RBC/mm³) on UA at Screening. If a potential confounder is present, a repeat UA may be performed during the Screening window; exclusion applies to confirmed microscopic hematuria on an evaluable specimen.
• Evidence of antecedent/recent GAS infection based on anti-DNase B titer ≥ the laboratory reported upper limit of normal (ULN) for the assay used at Screening. Participants with anti-DNase B titer ≥0.8×ULN and <ULN at the initial Screening visit are temporarily ineligible and may be re-screened with repeat anti-DNase B testing 7-21 days after the initial sample; participants will be excluded if the repeat anti-DNase B titer is ≥ULN or demonstrates a clinically meaningful increase of ≥20% relative to the initial screening value, in the absence of an alternative explanation.
• Positive GAS rapid NAAT at Screening or Day 1
• Any finding based on comprehensive TTE at Screening indicative of possible cardiac pathology, including valvular abnormalities defined as mild stenosis or regurgitation.
• Any finding on ECG that is indicative of possible cardiac pathology, including a prolonged PR interval or conduction abnormality
• Receipt of any investigational product within 30 days prior to enrollment into the study, currently participating in another study that includes receipt of an investigational product or procedure, or having plans to receive another investigational product(s) while on study
• Planned or actual administration of any licensed vaccine within 30 days before or after receipt of study vaccine, or within 14 days before or after receipt of study vaccine in the case of influenza and COVID-19 vaccines. Vaccines that are required emergently (e.g., tetanus vaccination in a participant with a contaminated wound) may be given at any time during the study.
• Received blood or blood product (including intravenous immunoglobulin) within 6 months of enrollment into the study
• Receipt of any immunosuppressive therapy, including systemic steroids at a dosage equivalent to ≥0.5 mg/kg/day of prednisone, chronic use of inhaled or nebulized high potency corticosteroids, or use of intra-articular or intrabursal corticosteroids within 1 year of the first study vaccination
• Body mass index (BMI) ≥32 kg/m2 or ≤18 kg/m2
• History of alcohol or drug abuse in the 5 years prior to enrollment, or any history of intravenous drug abuse
• Any medical, psychiatric, or social condition that in the judgment of the Investigator may interfere with the study objectives, impair a participant's ability to give informed consent, pose a risk to the participant, or prevent the participant from completing the study
• Employee of, or first degree relative of any person employed by the Sponsor, the contract research organization (CRO), the Investigator, study 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VAX-A1 Low; Participants will receive 2 doses of VAX-A1 administered via intramuscular injection at Day 1 and Month 2	Biological: VAX-A1 Low; 0.5mL of the low dose VAX-A1 will be administered into the deltoid muscle
Experimental: VAX-A1 Mid; Participants will receive 2 doses of VAX-A1 administered via intramuscular injection at Day 1 and Month 2	Biological: VAX-A1 Mid; 0.5mL of the mid dose VAX-A1 will be administered into the deltoid muscle
Experimental: VAX-A1 High; Participants will receive 2 doses of VAX-A1 administered via intramuscular injection at Day 1 and Month 2	Biological: VAX-A1 High; 0.5mL of the high dose VAX-A1 will be administered into the deltoid muscle
Placebo Comparator: Placebo; Participants will receive 2 doses of placebo administered via intramuscular injection at Day 1 and Month 2	Biological: Placebo; 0.5mL of placebo (normal saline) will be administered into the deltoid muscle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of solicited local reactions (redness, swelling, and pain at injection site)	up to 7 days after each vaccination
Frequency of solicited systemic adverse events (AE) (fever, headache, fatigue, muscle pain, rash, joint pain, nausea/vomiting, diarrhea)	up to 7 days after each vaccination
Frequency of laboratory abnormalities identified from protocol-scheduled safety laboratory assessments at 7 days after each vaccination and reported as AE	7 days after each vaccination
Frequency of unsolicited AE	up to 30 days after each vaccination
Frequency of medically attended AE (MAAE)	Up to 8 months after first vaccination
Frequency of new onset chronic illness (NOCI)	up to 8 months after the first vaccination
Frequency of serious adverse events (SAE)	from screening through up to 8 months after first vaccination
Occurrence of AE of special interest (AESI) (acute rheumatic fever [ARF], acute carditis [AC], and acute glomerulonephritis [AGN])	up to 8 months after the first vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
Median value of each safety laboratory parameter assessed 7 days after each vaccination	7 days after each vaccination
Median change from baseline to 7 days after each vaccination for each safety laboratory parameter	7 days after each vaccination
Serum IgG geometric mean titer (GMT) at each scheduled immunogenicity sample collection visit for each vaccine antigen (SLO, C5a pep, SpyAD, GAC)	Prior to each vaccination, 1 month after each vaccination and Month 8
Serum IgG geometric mean fold rise (GMFR) from baseline to each scheduled post-vaccination immunogenicity sample collection visit for each vaccine antigen (SLO, C5a pep, SpyAD, GAC)	Prior to each vaccination, 1 month after each vaccination and Month 8
Percentage of participants achieving serum IgG ≥2-fold increase from baseline at each scheduled post-vaccination immunogenicity sample collection visit for each vaccine antigen (SLO, C5a pep, SpyAD, GAC)	1 month after each vaccination and Month 8
Percentage of participants with serum IgG ≥ LLOQ of the assay at each scheduled immunogenicity sample collection visit for each vaccine antigen (SLO, C5a pep, SpyAD, GAC)	Prior to each vaccination, 1 month after each vaccination and Month 8

Collaborators and Investigators

• Sponsor: Vaxcyte, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: May 26, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Australia; Reactogenicity; Healthy Adults; Streptococcus pyogenes; Strep A
• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections
• Other Study ID Numbers: VAXA1-101

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. Sharing of data will require execution of a data-sharing agreement.
• 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.

Drug and device information, study documents

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