A Study of Three Different Doses of VAC52416 (ExPEC10V) in Adults Aged 60 to 85 Years in Stable Health

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, reactogenicity, and immunogenicity of 3 different doses of ExPEC10V and to select the optimal dose for further clinical development (Cohort 1). Cohort 2 is aimed to expand the dataset supporting the short- and long-term safety and immunogenicity of the optimal dose of ExPEC10V, selected from the primary analysis results of Cohort 1. Cohort 2 will include participants in stable health with a history of urinary tract infection (UTI) in the past 5 years and will be included in the study to support the plan for late stage development of ExPEC vaccine.

Detailed Description
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ExPEC10V (JNJ-69968054) is a 10-valent vaccine candidate in development for prevention of invasive extraintestinal pathogenic Escherichia coli (ExPEC) disease (IED) in adults 60 years of age and older. ExPEC10V consists of O-antigen polysaccharides (PSs) of the ExPEC serotypes O1A, O2, O4, O6A, O8, O15, O16, O18A, O25B and O75 separately bioconjugate to the carrier protein, a genetically detoxified form of exotoxin A (EPA) derived from Pseudomonas aeruginosa. Since, mechanism of action of conjugate vaccines in prevention of invasive disease is not expected to be affected by antibiotic resistance mechanisms, ExPEC10V vaccine may provide protection against IED caused by drug resistant and susceptible ExPEC serotypes. The study consists of two cohorts. Cohort 1 is comprised of three periods: a screening period (28 days), an observer-blind follow-up period (181 days) with vaccination on Day 1, and an open-label long term follow up (LTFU) period (from Day 182 until 5 years [Day 1826] post-vaccination). Cohort 2 is also comprised of three periods: a screening period (28 days), a double-blind follow-up period (181 days) with vaccination on Day 1, and a double-blind LTFU period (from Day 182 until 1 years [Day 366] post-vaccination). The end of Cohort 1 is considered as the Year 5 visit (Day 1826) for the last participant. The end of Cohort 2 is considered as the Year 1 visit (Day 366) for the last participant. Key immunogenicity assessments will include the assessment of ExPEC10V and ExPEC4V serotype-specific total immunoglobulin G antibody levels elicited by the vaccine and ExPEC10V and ExPEC4V serotype-specific functional antibodies. Key safety assessments include solicited local and systemic AEs, unsolicited AEs, SAEs, physical examinations, vital sign measurements, and, for Cohort 1 only, clinical laboratory tests. The total duration of the study is up to 5 years.

Official Title
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A Randomized, Observer-blind, First-in-Human Phase 1/2a Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Three Different Doses of VAC52416 (ExPEC10V) in Adults Aged 60 to 85 Years in Stable Health

Conditions
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Extraintestinal Pathogenic Escherichia Coli Prevention

Intervention / Treatment
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* Biological: ExPEC10V
* Biological: ExPEC4V
* Biological: Prevnar 13
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have a body mass index (BMI) of greater than (>) 18.5 or less than 40 kilogram per meter square (kg/m^2) Before randomization, a woman must be: postmenopausal - A postmenopausal state is defined as no menses for 12 months without an alternative medical cause; or not intending to conceive by any methods Must be healthy or medically stable Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study Willing and able to adhere to the lifestyle restrictions specified in this protocol Agrees not to donate blood until 12 weeks after receiving the study vaccine Exclusion Criteria: Acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature greater than equal to >=38.0 degree Celsius (100.4 degree Fahrenheit) within 24 hours prior to the administration of study vaccine, or, applicable for Cohort 2 only, an ongoing or suspected symptomatic urinary tract infection (UTI); enrollment at a later date is permitted (provided the screening window of 28 days is respected) History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence) Known allergies, hypersensitivity, or intolerance to ExPEC10V or its excipients Applicable for Cohort 1 only: known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of the constituents of the active control vaccines) Contraindication to intramuscular (IM) injections and blood draws example, bleeding disorders Abnormal function of the immune system Has had major psychiatric illness and/or drug substance or alcohol abuse in the past 12 months

Ages Eligible for Study
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Minimum Age: 60 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: ExPEC10V (Low Dose)<br>Participants will be randomized to receive a single intramuscular (IM) injection of low dose ExPEC10V on Day 1. | Biological: ExPEC10V<br>* Participants will receive a single IM injection of ExPEC10V (1 of 3 doses [low or medium or high]) in Cohort 1 and ExPEC10V selected dose (based on the primary analysis results of Cohort 1) in Cohort 2 on Day 1.<br>* Other names: VAC52416;|
| Experimental: Cohort 1: ExPEC10V (Medium dose)<br>Participants will be randomized to receive a single IM injection of medium dose ExPEC10V on Day 1. | Biological: ExPEC10V<br>* Participants will receive a single IM injection of ExPEC10V (1 of 3 doses [low or medium or high]) in Cohort 1 and ExPEC10V selected dose (based on the primary analysis results of Cohort 1) in Cohort 2 on Day 1.<br>* Other names: VAC52416;|
| Experimental: Cohort 1: ExPEC10V (High dose)<br>Participants will be randomized to receive a single IM injection of high dose ExPEC10V on Day 1. | Biological: ExPEC10V<br>* Participants will receive a single IM injection of ExPEC10V (1 of 3 doses [low or medium or high]) in Cohort 1 and ExPEC10V selected dose (based on the primary analysis results of Cohort 1) in Cohort 2 on Day 1.<br>* Other names: VAC52416;|
| Experimental: Cohort 1: ExPEC4V<br>Participants will be randomized to receive a single IM injection of ExPEC4V on Day 1. | Biological: ExPEC4V<br>* Participants will receive a single IM injection of ExPEC4V on Day 1.<br>* Other names: JNJ-63871860;|
| Experimental: Cohort 1: Prevnar 13<br>Participants will be randomized to receive a single IM injection of Prevnar 13 on Day 1. | Biological: Prevnar 13<br>* Participants will receive a single IM injection of Prevnar 13 on Day 1.<br>|
| Experimental: Cohort 2: ExPEC10V<br>Participants will be randomized to receive a single IM injection of selected dose of ExPEC10V on Day 1. The ExPEC10V dose used in Cohort 2 will be based on the primary analysis (Day 30) results of Cohort 1. | Biological: ExPEC10V<br>* Participants will receive a single IM injection of ExPEC10V (1 of 3 doses [low or medium or high]) in Cohort 1 and ExPEC10V selected dose (based on the primary analysis results of Cohort 1) in Cohort 2 on Day 1.<br>* Other names: VAC52416;|
| Placebo Comparator: Cohort 2: Placebo<br>Participants will be randomized to receive a single IM injection of matching placebo on Day 1. | Biological: Placebo<br>* Participants will receive single IM injection of matching placebo on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1 and Cohort 2: Number of Participants with Solicited Local and Systemic Adverse Events (AEs) Collected for 14 days post-Vaccination | Number of participants with solicited local and systemic AEs will be reported. Solicited local AEs (pain/tenderness, erythema, and swelling at the injection site) and solicited systemic AEs (oral body temperature, headache, fatigue, nausea, and myalgia) will be noted in the participant diary for 14 days post-vaccination. | From Day 1 to Day 15 | 
| Cohort 1 and Cohort 2: Number of Participants with Unsolicited Adverse Events From the Administration of Study Vaccine until 29 Days post-Vaccination | Number of participants with unsolicited AEs will be reported. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Unsolicited adverse events are all adverse events for which the participant is not specifically questioned in the participant ediary. | From Day 1 to Day 30 | 
| Cohort 1 and Cohort 2: Number of Participants with Serious Adverse Events (SAE's) from the Administration of the Study Vaccine until Day 181 | Number of participants with SAEs will be reported. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life threatening experience, is a congenital anomaly/birth defect, is suspected transmission of any infectious agent via a medicinal product, is medically important, and may jeopardize participant or may require medical or surgical intervention to prevent one of the outcomes listed above. | Up to Day 181 | 
| Cohort 1: Antibody Titers for ExPEC10V as Determined by Multiplex Electrochemiluminescent (ECL)-based Immunoassay on Day 15 | Antibody titers for ExPEC10V will be determined by multiplex ECL-based immunoassay. | On Day 15 | 
| Cohort 1: Antibody Titers for ExPEC10V as Determined by Multiplex Opsonophagocytic Assay (MOPA) on Day 15 | Antibody titers for ExPEC10V will be determined by MOPA. | On Day 15 | 
| Cohort 2: Antibody Titers for ExPEC10V as Determined by Multiplex ECL-based Immunoassay on Day 30 | Antibody titers for ExPEC10V will be determined by multiplex ECL-based immunoassay. | On Day 30 | 
| Cohort 2: Antibody Titers for ExPEC10V as Determined by MOPA on Day 30 | Antibody titers for ExPEC10V will be determined by MOPA. | On Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Antibody Titers for ExPEC10V as Determined by Multiplex ECL-based Immunoassay and MOPA to find Correlation Between Multiplex ECL-based Immunoassay and MOPA | Antibody titers for ExPEC10V as determined by multiplex ECL-based immunoassay and MOPA to find correlation between multiplex ECL-based immunoassay and MOPA | Day 15 | 
| Cohort 1: Antibody Titers for ExPEC10V as Determined by Multiplex ECL-based Immunoassay on Days 30, 181, 366, 731, 1096, 1461, and 1826 | Antibody titers for ExPEC10V will be determined by multiplex ECL-based immunoassay. | On Days 30, 181, 366, 731, 1096, 1461, and 1826 | 
| Cohort 1: Antibody Titers for ExPEC10V as Determined by MOPA on Days 30, 181, 366, 731, 1096, 1461, and 1826 | Antibody titers for ExPEC10V will be determined by MOPA. | On Days 30, 181, 366, 731, 1096, 1461, and 1826 | 
| Cohort 2: Antibody Titers for ExPEC10V as Determined by Multiplex ECL-based Immunoassay and MOPA to find Correlation Between Multiplex ECL-based Immunoassay and MOPA | Antibody titers for ExPEC10V as determined by multiplex ECL-based immunoassay and MOPA to find correlation between multiplex ECL-based immunoassay and MOPA | Day 30 | 
| Cohort 2: Antibody Titers for ExPEC10V as Determined by Multiplex ECL-based Immunoassay on Days 15, 181, and 366 | Antibody titers for ExPEC10V will be determined by multiplex ECL-based immunoassay. | On Days 15, 181, and 366 | 
| Cohort 2: Antibody Titers for ExPEC10V as Determined by MOPA on Days 181, and 366 | Antibody titers for ExPEC10V will be determined by MOPA. | On Days 181, and 366 | 
| Cohort 1 and Cohort 2: Number of Participants with Serious Adverse Events Related to the Study Intervention or Study Procedures From Day 182 Until the end of the Study | Number of participants with SAEs related to the study intervention or study procedures will be reported. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life threatening experience, is a congenital anomaly/birth defect, is suspected transmission of any infectious agent via a medicinal product, is medically important, and may jeopardize participant or may require medical or surgical intervention to prevent one of the outcomes listed above. | Cohort 1: Day 1826 and Cohort 2: Day 366 |