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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pneumococcal Vaccines

Intervention / Treatment
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* Biological: 0.5 ml dose of 1.1 mcg VAX-24
* Biological: 0.5 ml dose of PCV20
* Biological: 0.5 ml dose of 2.2 mcg VAX-24
* Biological: 0.5 ml dose of 2.2/4.4 mcg VAX-24


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female infant ≥42 days to ≤89 days (inclusive). Full-term infant at least 37 weeks gestational age at birth. 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.* Able to attend all scheduled visits and comply with the study procedures. Subject's parent/legal guardian is able to read and understands the study procedures, alternate treatments, risks and benefits, and provides written informed consent. 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. 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: 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. Previous receipt of a licensed or investigational vaccine (excluding 1 dose hepatitis B vaccine). Known hypersensitivity to any vaccine. Known or suspected impairment of immunological function (e.g., asplenia, HIV, primary immunodeficiency). Use of any immunosuppressive therapy (Note: topical and inhaled/nebulized steroids are permitted). History of failure to thrive. Subject has a coagulation disorder contraindicating IM vaccination. Subject or his/her mother have documented hepatitis B surface antigen-positive. Has a known neurologic or cognitive behavioral disorder. Has a known clinically significant congenital malformation or serious chronic disorder. Receipt of a blood transfusion or blood products, including immunoglobulins. 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. Any infant who cannot be adequately followed for safety according to the protocol plan. Any other reason that in the opinion of the investigator may interfere with the evaluation required by the study.

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 89 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VAX-24 Low<br>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. | Biological: 0.5 ml dose of 1.1 mcg VAX-24<br>* 24 valent pneumococcal conjugate vaccine<br>|
| Experimental: VAX-24 Mid<br>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. | Biological: 0.5 ml dose of 2.2 mcg VAX-24<br>* 24 valent pneumococcal conjugate vaccine<br>|
| Experimental: VAX-24 Mixed<br>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. | Biological: 0.5 ml dose of 2.2/4.4 mcg VAX-24<br>* 24 valent pneumococcal conjugate vaccine<br>|
| Active Comparator: PCV20<br>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. | Biological: 0.5 ml dose of PCV20<br>* 20 valent pneumococcal conjugate vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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24 valent PCV, Pneumonia, Pneumococcal Infection