Study to Evaluate a 25-Valent Pneumococcal Conjugate Vaccine

Study Overview
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Brief Summary
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A first-in-human, Phase 1 trial to evaluate safety, tolerability, and immunogenicity of Inventprise's (IVT) 25-valent pneumococcal conjugate vaccine (IVT PCV-25)

Detailed Description
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A first-in-human, multicenter, randomized, active-controlled, observer-blind Phase 1 study of IVT PCV-25 designed to evaluate the safety, tolerability, and immunogenicity of the vaccine. Adult subjects will be randomized 1:1 to receive either IVT PCV-25 or Prevnar 20™.

Official Title
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A Phase 1, Multicenter, Randomized, Active-Controlled, Observer-Blind, Study to Evaluate the Safety, Tolerability, and Immunogenicity of Inventprise's 25-Valent Pneumococcal Conjugate Vaccine in Healthy PCV-Naïve Adults (18 Through 40 Years)

Conditions
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Pneumococcal Vaccines

Intervention / Treatment
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* Biological: IVT PCV-25
* Biological: PCV 20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults who are 18 through 40 years old on the day of randomization (Day 1). Subject, or subject's LAR, must provide voluntary written informed consent for the subject to participate in the study. Subject or subject's LAR must be able to comprehend and comply with study requirements and procedures and must be willing and able to return for all scheduled follow-up visits. There will be an allowance though not a requirement for COVID-19 vaccination in all participants in compliance with Canadian national recommendations. Adult female subjects who are not surgically sterile must have a negative serum pregnancy test at screening and negative urine pregnancy test prior to vaccination. Exclusion Criteria: Use of any investigational medicinal product within 90 days prior to randomization or planned use of such a product during the period of study participation. Adults who have previously been vaccinated against S. pneumoniae. History of microbiologically confirmed invasive disease caused by S. pneumoniae. History of allergic disease or history of a serious reaction to any prior vaccination or known hypersensitivity to any component of the study vaccines. Known or suspected allergy to PEG. History of angioedema. Any abnormal vital sign deemed clinically relevant by the PI. Acute illness (moderate or severe) and/or fever (body temperature of ≥ 38.0°C) Use of antibiotics (oral or parenteral) within 5 days of randomization. History of administration of any non-study vaccine (e.g. influenza; COVID-19 vaccine) within 14 days of first administration of study vaccine or planned vaccination prior to 14 days post-vaccination blood draw. Chronic administration (defined as more than 14 consecutive days) of immunosuppressant or other immune modifying drugs prior to the administration of the study vaccine (and within the 6 months prior to administration of the study vaccine in the case of adults), including the use of glucocorticoids. The use of topical and inhaled glucocorticoids will be permitted. Administration of immunoglobulins and/or any blood products within the 6 months prior to administration of the study vaccine, or anticipation of such administration during the study period. History of known disturbance of coagulation or blood disorder that could cause anemia or excess bleeding (e.g., thalassemia, coagulation factor deficiencies, severe anemia). Any medical or social condition that in the opinion of the PI , may interfere with the study objectives, pose a risk to the subject, or prevent the subject from completing the study follow-up. Subject is an employee of, or direct descendant (child or grandchild) of any person employed by the Sponsor, PATH, the CRO, the PI. Any screening laboratory test result outside the normal range and with toxicity score ≥ 2, unless allowed by the PI and PATH Medical Officer when a toxicity score and the normal range overlap significantly. A subject may repeat each laboratory assessment once during the screening period, with the most recent laboratory value being used for evaluation of exclusion criteria. A positive serologic test for human immunodeficiency virus (HIV)-1 or HIV-2 (HIV 1/2 Ab), hepatitis B (HBsAg) or hepatitis C (HCV Ab). History of malignancy, excluding non-melanoma skin and cervical carcinoma in situ. Recent history (within the past year) or signs of alcohol or substance abuse. History of major psychiatric disorder. Female adult subjects who are pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

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
Interventional Model Description: Single center, randomized, active-controlled, observer-blind Phase 1study in which adults were randomized in a 1:1 ratio to evaluate safety and tolerability of IVT PCV 25 to comparator.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adult Cohort Group 1<br>Participants will receive a single 0.5mL dose of IVT PCV-25 administered by intramuscular injection on Day 1 | Biological: IVT PCV-25<br>* 25 valent pneumococcal conjugate vaccine<br>|
| Active Comparator: Adult Cohort Group 2<br>Participants will receive a single 0.5mL dose of PCV 20 administered by intramuscular injection on Day 1 | Biological: PCV 20<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 |
| --- | --- | --- |
| Adult Safety: solicited local and systemic adverse events | Number and severity of solicited local and systemic adverse events (AEs) | 7 days post-vaccination (Day 8) | 
| Adult Safety: clinically significant hematological and biochemical measurements | Number, severity, and relatedness of clinically significant hematological and biochemical measurements | 7 days post-vaccination (Day 8) | 
| Adult Safety: unsolicited adverse events | Number, severity, and relatedness of all unsolicited AEs | 28 days post-vaccination (Day 29) | 
| Adult Safety: related serious adverse events | Number, severity, and relatedness of serious adverse events (SAEs) | through 6 months post last vaccination (Day 169) | 
| Adult Safety: newly diagnosed chronic medical conditions | Number of newly diagnosed chronic medical conditions | through 6 months post last vaccination (Day 169) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adult Immunogenicity: immunoglobulin G (IgG) geometric mean concentration (GMC) | Serotype-specific IgG GMCs | 28 days post-vaccination (Day 29) | 
| Adult Immunogenicity: Geometric Mean Fold Rise (GMFR) | Geometric Mean Fold Rise (GMFR) from baseline in serotype-specific IgG GMCs | 28 days post-vaccination (Day 29) | 
| Adult Immunogenicity: opsonophagocytosis assay (OPA) geometric mean titers (GMTs) | Serotype-specific OPA GMTs | 28 days post-vaccination (Day 29) | 
| Adult Immunogenicity: GMFR OPA GMTs | GMFR (from baseline) in serotype-specific OPA GMTs | 28 days post-vaccination (Day 29) |