Clinical trial NCT03819049: A Study of Three Different Doses of VAC52416 (ExPEC10V) in Adults Aged 60 to 85 Years in Stable Health
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Extraintestinal Pathogenic Escherichia Coli Prevention
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-01-28
Enrollment: 836
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cohort 1: Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) for 14 Days After Vaccination on Day 1
timeFrame: Up to 14 days post vaccination on Day 1 (from Day 1 up to Day 15)
measure: Cohort 1: Number of Participants With Solicited Systemic Adverse Events (AEs) Collected for 14 Days After Vaccination on Day 1
timeFrame: Up to 14 days post vaccination on Day 1 (from Day 1 up to Day 15)
measure: Cohort 1: Number of Participants With Unsolicited Adverse Events (AEs) up to 29 Days After Vaccination on Day 1
timeFrame: Up to 29 days post vaccination on Day 1 (from Day 1 up to Day 30)
measure: Cohort 1: Number of Participants With Serious Adverse Events (SAEs) up to Day 181
timeFrame: Day 1 (post vaccination) up to Day 181
measure: Cohort 2: Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) Collected for 14 Days After Vaccination on Day 1
timeFrame: Up to 14 days post vaccination on Day 1 (from Day 1 up to Day 15)
measure: Cohort 2: Number of Participants With Solicited Systemic Adverse Events (AEs) Collected for 14 Days After Vaccination on Day 1
timeFrame: Up to 14 days post vaccination on Day 1 (from Day 1 up to Day 15)
measure: Cohort 2: Number of Participants With Unsolicited Adverse Events (AEs) 29 Days After Vaccination on Day 1
timeFrame: Up to 29 days post vaccination on Day 1 (from Day 1 up to Day 30)
measure: Cohort 2: Number of Participants With Serious Adverse Events (SAEs) up to Day 181
timeFrame: Day 1 (post vaccination) up to Day 181
measure: Cohort 1: Geometric Mean Titers (GMTs) of Serotype-specific Total Immunoglobulin G (IgG) Serum Antibodies as Measured by Multiplex Electrochemiluminescent (ECL) Based Immunoassay on Day 15
timeFrame: Day 15
measure: Cohort 1: Geometric Mean Ratio (GMR) of Fold Changes From Baseline for Serotype Specific Antibodies as Measured by Multiplex ECL Based Immunoassay on Day 15
timeFrame: Baseline (Day 1, pre-vaccination) and Day 15
measure: Cohort 1: Percentage of Participants With a Greater Than or Equal to (>=) 2-Fold and >=4-Fold Increase From Baseline in Serotype Specific Serum Antibody Titers as Measured by Multiplex ECL Based Immunoassay on Day 15
timeFrame: Baseline (Day 1, pre-vaccination) and Day 15
measure: Cohort 1: Geometric Mean Titers (GMT) of Serotype-specific Total Immunoglobulin G (IgG) Serum Antibodies as Measured by Multiplex Opsonophagocytic Assay (MOPA) on Day 15
timeFrame: Day 15
measure: Cohort 1: Geometric Mean Ratio (GMR) of Fold Changes From Baseline for Serotype Specific Antibodies as Measured by MOPA on Day 15
timeFrame: Baseline (Day 1, pre-vaccination), Day 15
measure: Cohort 1: Percentage of Participants With a >= 2-Fold and >=4-Fold Increase in Serotype-specific Serum Antibody Titers Measured by MOPA on Day 15
timeFrame: Baseline (Day 1, pre-vaccination) and Day 15
measure: Cohort 2: Geometric Mean Titers (GMTs) of Serotype-specific Total Immunoglobulin G (IgG) Serum Antibodies as Measured by Multiplex ECL Based Immunoassay on Day 30
timeFrame: At Day 30
measure: Cohort 2: Geometric Mean Ratio (GMR) of Serotype-specific Antibodies Measured by Multiplex ECL Based Immunoassay on Day 30
timeFrame: Baseline (Day 1, pre-vaccination) and Day 30
measure: Cohort 2: Percentage of Participants With a >=2-Fold and >=4-Fold Increase From Baseline in Serotype Specific Serum Antibody Titers as Measured by Multiplex ECL Based Immunoassay on Day 30
timeFrame: Baseline (Day 1, pre-vaccination) and Day 30
measure: Cohort 2: Geometric Mean Titer (GMT) of Serotype-specific Total Immunoglobulin G (IgG) Serum Antibodies as Measured by Multiplex Opsonophagocytic Assay (MOPA) on Day 30
timeFrame: At Day 30
measure: Cohort 2: Geometric Mean Ratio (GMR) of Fold Changes From Baseline for Serotype Specific Antibodies as Measured by MOPA on Day 30
timeFrame: Baseline (Day 1, pre-vaccination) and Day 30
measure: Cohort 2: Percentage of Participants With a >= 2-Fold and >=4-Fold Increase in Serotype-specific Serum Antibodies Titers Measured by MOPA on Day 30
timeFrame: Baseline (Day 1, pre-vaccination) and Day 30
Secondary outcomes:
measure: Cohort 1: Correlation Between the Multiplex ECL-Based Immunoassay and the MOPA Functional Titers by Serotypes on Day 15
timeFrame: Day 15
measure: Cohort 1: Geometric Mean Titers (GMTs) of Serotype-specific Total Immunoglobulin G (IgG) Serum Antibodies as Measured by Multiplex ECL Based Immunoassay on Days 30 and 181
timeFrame: Days 30 and 181
measure: Cohort 1: Percentage of Participants With a Greater Than or Equal to (>=) 2-Fold and >=4-Fold Increase From Baseline in Serotype Specific Serum Antibody Titers as Measured by Multiplex ECL Based Immunoassay on Days 30 and 181
timeFrame: Day 1 (pre-vaccination) and Days 30 and 181
measure: Cohort 1: Geometric Mean Ratio (GMR) of Serotype-specific Antibodies Measured by Multiplex ECL Based Immunoassay on Days 30 and 181
timeFrame: Baseline (Day 1, pre-vaccination) and Days 30 and 181
measure: Cohort 1: Geometric Mean Titer (GMT) of Serotype-specific Total Immunoglobulin G (IgG) Serum Antibodies as Measured by Multiplex Opsonophagocytic Assay (MOPA) on Days 30 and 181
timeFrame: At Days 30 and 181
measure: Cohort 1: Geometric Mean Ratio (GMR) of Fold Changes From Baseline for Serotype Specific Antibodies as Measured by MOPA on Days 30 and 181
timeFrame: Baseline (Day 1, pre-vaccination), and Days 30 and 181
measure: Cohort 1: Percentage of Participants With a >= 2-Fold and >=4-Fold Increase in Serotype-specific Serum Antibody Titers Measured by MOPA on Days 30 and 181
timeFrame: Baseline (Day 1, pre-vaccination) and Days 30 and 181
measure: Cohort 1: Number of Participants With Serious Adverse Events (SAEs) Related to Study Vaccine or Study Procedure From Day 182 up to End of Study (Day 1826)
timeFrame: From Day 182 up to end of study (Day 1826)
measure: Cohort 1: Geometric Mean Titers (GMTs) of Serotype-specific Total Immunoglobulin G (IgG) Serum Antibodies as Measured by Multiplex ECL Based Immunoassay on Days 366, 731, 1096, 1461 and 1826
timeFrame: Days 366, 731, 1096, 1461 and 1826
measure: Cohort 1: Percentage of Participants With a >=2-Fold and >=4-Fold Increase From Baseline in Serotype Specific Serum Antibody Titers as Measured by Multiplex ECL Based Immunoassay on Days 366, 731, 1096, 1461 and 1826
timeFrame: Baseline (Day 1, pre-vaccination) and Days 366, 731, 1096, 1461, 1826
measure: Cohort 1: Geometric Mean Ratio (GMR) of Serotype-specific Antibodies Measured by Multiplex ECL Based Immunoassay on Days 366, 731, 1096, 1461 and 1826
timeFrame: Baseline (Day 1, pre-vaccination) and Days 366, 731, 1096, 1461, 1826
measure: Cohort 1: Geometric Mean Titer (GMT) of Serotype-specific Total Immunoglobulin G (IgG) Serum Antibodies as Measured by MOPA on Days 366, 731, 1096, 1461 and 1826
timeFrame: Days 366, 731, 1096, 1461 and 1826
measure: Cohort 1: Geometric Mean Ratio (GMR) of Fold Changes From Baseline for Serotype Specific Antibodies as Measured by MOPA on Days 366, 731, 1096, 1461 and 1826
timeFrame: Baseline (Day 1, pre-vaccination) and Days 366, 731, 1096, 1461, 1826
measure: Cohort 1: Percentage of Participants With a >= 2-Fold and >=4-Fold Increase in Serotype-specific Serum Antibody Titers Measured by MOPA on Days 366, 731, 1096, 1461 and 1826
timeFrame: Baseline (Day 1, pre-vaccination) and Days 366, 731, 1096, 1461, 1826
measure: Cohort 2: Correlation Between the Multiplex ECL-Based Immunoassay and the MOPA Functional Titers by Serotype on Day 30
timeFrame: At Day 30
measure: Cohort 2: Geometric Mean Titers (GMTs) of Serotype-specific Total Immunoglobulin G (IgG) Serum Antibodies as Measured by Multiplex ECL Based Immunoassay on Days 15 and 181
timeFrame: At Days 15 and 181
measure: Cohort 2: Geometric Mean Ratio (GMR) of Serotype-specific Antibodies Measured by Multiplex ECL Based Immunoassay on Days 15 and 181
timeFrame: Baseline (Day 1, pre-vaccination), Days 15 and 181
measure: Cohort 2: Percentage of Participants With a >= 2-Fold and >=4-Fold Increase in Serotype-specific Serum Antibody Titers Measured by Multiplex ECL Based Immunoassay on Days 15 and 181
timeFrame: Baseline (Day 1, pre-vaccination) and Days 15 and 181
measure: Cohort 2: Geometric Mean Titers (GMTs) of Serotype-specific Antibodies Against Specified Antigens Measured by MOPA on Day 181
timeFrame: At Day 181
measure: Cohort 2: Percentage of Participants With a >= 2-Fold and >=4-Fold Increase in Serotype-specific Serum Antibody Titers Measured by MOPA on Day 181
timeFrame: Baseline (Day 1, pre-vaccination) and Day 181
measure: Cohort 2: Geometric Mean Ratio (GMR) of Serotype-specific Antibodies Measured by MOPA on Day 181
timeFrame: Baseline (Day 1, pre-vaccination), Day 181
measure: Cohort 2: Number of Participants With Serious Adverse Events (SAEs) Related to Study Vaccine or Study Procedure From Day 182 up to End of Study (Day 1826)
timeFrame: From Day 182 up to end of study (Day 1826)
measure: Cohort 2: Geometric Mean Titers (GMTs) of Serotype-specific Antibodies Against Specified Antigens Measured by Multiplex ECL Based Immunoassay on Day 366
timeFrame: At Day 366
measure: Cohort 2: Percentage of Participants With a >= 2-Fold and >=4-Fold Increase in Serotype-specific Serum Antibody Titers Measured by Multiplex ECL Based Immunoassay on Day 366
timeFrame: Baseline (Day 1, pre-vaccination) and Day 366
measure: Cohort 2: Geometric Mean Ratio (GMR) of Serotype-specific Antibodies Measured by Multiplex ECL Based Immunoassay on Day 366
timeFrame: Baseline (Day 1, pre-vaccination), Day 366
measure: Cohort 2: Geometric Mean Titers (GMTs) of Serotype-specific Antibodies Against Specified Antigens Measured by MOPA on Day 366
timeFrame: At Day 366
measure: Cohort 2: Percentage of Participants With a >= 2-Fold and >=4-Fold Increase in Serotype-specific Serum Antibody Titers Measured by MOPA on Day 366
timeFrame: Baseline (Day 1, pre-vaccination) and Day 366
measure: Cohort 2: Geometric Mean Ratio (GMR) of Serotype-specific Antibodies Measured by MOPA on Day 366
timeFrame: Baseline (Day 1, pre-vaccination), Day 366
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Optimal Research
state: Alabama
city: Melbourne
country: United States
facility: Optimal Research
state: Florida
city: Miami
country: United States
facility: Qps-Mra, Llc
state: Florida
city: Peoria
country: United States
facility: Optimal Research
state: Illinois
city: Evansville
country: United States
facility: Synexus Clinical Research US Inc
state: Indiana
city: Lenexa
country: United States
facility: Johnson County Clin-Trials
state: Kansas
city: Richfield
country: United States
facility: Synexus Clinical Research US Inc
state: Minnesota
city: Manhattan
country: United States
facility: Synexus Clinical Research US Inc
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc
state: New York
city: Akron
country: United States
facility: Synexus Clinical Research US Inc
state: Ohio
city: Columbus
country: United States
facility: Synexus Clinical Research US Inc
state: Ohio
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Alken
country: Belgium
facility: Anima
city: Luik
country: Belgium
facility: ATC Pharma
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
city: Nantes
country: France
facility: CHU Nantes
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: APHP - Hopital Bichat - Claude Bernard
city: Pierre Benite
country: France
facility: CHU Lyon Sud
city: Rennes
country: France
facility: Chu Rennes Hopital Pontchaillou
city: Tours
country: France
facility: CHRU Tours Hopital Bretonneau
city: Almere
country: Netherlands
facility: EB Flevo Research
city: Groningen
country: Netherlands
facility: PRA Health Sciences
city: Barcelona
country: Spain
facility: Hosp. Del Mar
city: Córdoba
country: Spain
facility: Hosp Reina Sofia
city: Madrid
country: Spain
facility: Hosp. Univ. de La Princesa
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hosp. Virgen Macarena
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: