Dose-Ranging Study to Evaluate a 25-Valent Pneumococcal Conjugate Vaccine

Study Overview
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Brief Summary
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Phase 2 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 Phase 2 multicenter, randomized, active-controlled, observer-blind study to evaluate safety, tolerability, and immunogenicity of three formulations of IVT PCV-25, a 25 valent conjugated pneumococcal vaccine with adjuvant. Adult participants will be randomized in a 4:3:2:2 ratio to receive 1 of 3 formulations or control.

Official Title
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A Phase 2, Multicenter, Randomized, Active-Controlled, Observer-Blind, Dose-Ranging Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 25-Valent Pneumococcal Conjugate Vaccine in Healthy PCV-Naïve Adults

Conditions
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Pneumococcal Vaccines

Intervention / Treatment
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* Biological: IVT PCV-25 Formulation A
* Biological: IVT PCV-25 Formulation B
* Biological: IVT PCV-25 Formulation C
* Biological: PCV 20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults who are 18 through 49 years old on the day of randomization (Day 1). Participant must provide voluntary written informed consent to participate in the study. Participant must be able to comprehend and comply with study requirements and procedures and be willing and able to return for all scheduled follow-up visits. Adult female participants who are not surgically sterile must have a negative pregnancy test at screening and negative pregnancy test prior to vaccination and must agree to employ a highly effective method to avoid pregnancy through Day 57 of the study. 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 (including angioedema) or history of a serious reaction to any prior vaccination or known hypersensitivity to any component of the study vaccines, including PEG. Any abnormal vital sign deemed clinically relevant by the PI. Acute illness at time of randomization (moderate or severe) and/or fever (body temperature of ≥ 38.0°C) History of any non-study vaccine administration within 14 days of study vaccine administration. No planned vaccines until after Day 29 (Visit 3). 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), 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. Any medical or social condition that in the opinion of the PI , may interfere with the study objectives, pose a risk to the participant, or prevent the participant from completing the study follow-up. Any screening laboratory test result outside the normal range and with toxicity score ≥ 2, unless allowed by study team. 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 participants who are pregnant or breastfeeding. Participant is an employee of, or direct descendant (child or grandchild) of any person employed by the Sponsor, PATH, the Contract Research Organization (CRO), the PI.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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: Multicenter, randomized, active-controlled, observer-blind study to evaluate safety, tolerability, and immunogenicity of three formulations of IVT PCV-25 in which healthy adult participants will be randomized in a 4:3:2:2 ratio to receive 1 of 3 formulations or control.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Participants will receive a single 0.5mL dose of IVT PCV-25 Formulation A administered by intramuscular injection on Day 1 | Biological: IVT PCV-25 Formulation A<br>* 25 valent pneumococcal conjugate vaccine containing low dose polysaccharide and low dose adjuvant<br>|
| Experimental: Group B<br>Participants will receive a single 0.5mL dose of IVT PCV-25 Formulation B administered by intramuscular injection on Day 1 | Biological: IVT PCV-25 Formulation B<br>* 25 valent pneumococcal conjugate vaccine containing low dose polysaccharide and high dose adjuvant<br>|
| Experimental: Group C<br>Participants will receive a single 0.5mL dose of IVT PCV-25 Formulation C administered by intramuscular injection on Day 1 | Biological: IVT PCV-25 Formulation C<br>* 25 valent pneumococcal conjugate vaccine containing high dose polysaccharide and high dose adjuvant<br>|
| Active Comparator: Group D<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 |
| --- | --- | --- |
| Solicited local adverse events (AEs) | Number and severity of solicited local AEs | 7 days post-vaccination (Day 8) | 
| Solicited systemic AEs | Number and severity of solicited systemic AEs | 7 days post-vaccination (Day 8) | 
| Unsolicited AEs | Number and severity of unsolicited AEs | 28 days post-vaccination (Day 29) | 
| Severe adverse events (SAEs) | Number of SAEs | 6 months post-vaccination (Day 169) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunoglobulin G (IgG) geometric mean concentration (GMC) | Serotype-specific IgG GMCs | Baseline (Day 1) and 28 days post-vaccination (Day 29) | 
| IgG geometric mean fold rise (GMFR) | IgG GMFR as measured by serotype-specific IgG GMCs from baseline | 28 days post-vaccination (Day 29) | 
| IgG four-fold rise | Percentage of participants with four-fold IgG GMC rise or greater as measured by serotype-specific IgG GMCs from baseline | 28 days post-vaccination (Day 29) | 
| IgG GMC ratio | IgG GMC ratio between IVT PCV-25 and Prevnar 20 groups as measured by serotype-specific IgG GMCs | 28 days post-vaccination (Day 29) | 
| IgG GMFR ratio | IgG GMFR ratio between IVT PCV-25 and Prevnar 20 groups as measured by serotype-specific IgG GMCs | 28 days post-vaccination (Day 29) | 
| OPA geometric mean titer (GMT) | Serotype-specific OPA GMTs | Baseline (Day 1) and 28 days post-vaccination (Day 29) | 
| OPA GMFR | OPA GMFR between IVT PCV-25 and Prevnar 20 groups as measured by serotype-specific OPA GMTs from baseline | 28 days post-vaccination (Day 29) | 
| OPA GMT ratio | OPA GMT ratio between IVT PCV-25 and Prevnar 20 groups as measured by serotype-specific OPA GMTs | 28 days post-vaccination (Day 29) | 
| OPA GMFR ratio | OPA GMFR ratio between IVT PCV-25 and Prevnar 20 groups as measured by serotype-specific OPA GMTs | 28 days post-vaccination (Day 29) |