Group A Streptococcal Infection
Conditions
Keywords
Strep A, Streptococcus pyogenes, Safety, Reactogenicity, Immunogenicity, Healthy Adults, Australia
Brief summary
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.
Interventions
BIOLOGICALPlacebo
0.5mL of placebo (normal saline) will be administered into the deltoid muscle
BIOLOGICALVAX-A1 Low
0.5mL of the low dose VAX-A1 will be administered into the deltoid muscle
BIOLOGICALVAX-A1 Mid
0.5mL of the mid dose VAX-A1 will be administered into the deltoid muscle
BIOLOGICALVAX-A1 High
0.5mL of the high dose VAX-A1 will be administered into the deltoid muscle
Sponsors
Vaxcyte, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| 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
| 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 |
Countries
Australia
Contacts
CONTACTClinical Development
Outcome results
None listed