A Study in Healthy Adults to Evaluate the Safety and Immunogenicity of Different Doses of JNJ-63871860

Randomized, Double-blind, Placebo-controlled, Multicenter Phase 2 Study in Healthy Adults to Evaluate the Safety and Immunogenicity of Different Doses of JNJ-63871860

The purpose of this study is to evaluate the safety, tolerability of different doses of JNJ-63871860 (ExPEC4V) in participants greater than or equal to (>=)18 years of age and to evaluate the dose-dependent immunogenicity of ExPEC as measured by enzyme-linked immunosorbent assay (ELISA).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: ExPEC4V (4 : 4 : 4 : 4); Drug: Placebo; Biological: ExPEC4V (4 : 4 : 4 : 8); Biological: ExPEC4V (8 : 8 : 8 : 8); Biological: ExPEC4V (8 : 8 : 8 : 16); Biological: ExPEC4V (16 : 16 : 16 : 16)

Detailed Description

This is a Phase 2, double-blind (neither the researchers nor the participants know what treatment the participant is receiving), randomized (study medication assigned to participants by chance), placebo-controlled (an inactive substance; a pretend treatment [with no drug in it] that is compared in a clinical trial with a drug to test if the drug has a real effect), parallel group, multicenter (when more than one hospital work on a medical research study) study, with a single-blind, long-term follow-up to Year 3. The study will be split into 2 phases, a double-blind phase with screening (Day -12 to Day 1), Vaccination (Day 1) and Safety and Immunogenicity Follow-up (Day 1 up to Day 360), and a single-blind long-term follow-up phase thereafter until Year 3 for participants in placebo and two ExPEC4V dose groups selected based on the primary (Day 30) analysis. Participants will be stratified in 2 age groups (>=18 to less than [<] 50 years and >=50 years) and in each dosing group in each stratum randomized to a single vaccination with 1 of 5 doses of ExPEC4V or placebo. The duration of the double-blind phase (from randomization/vaccination) will be approximately 360 days for placebo participants and participants in the dose group selected based on the primary analysis, and approximately 180 days for the participants in the other groups. The duration of the single-blind long-term follow-up phase will be approximately 2 years after the double-blind phase for placebo participants and participants in the selected dose group. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 848
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States
  • Florida
    • Hollywood, Florida, United States
    • Leesburg, Florida, United States
    • Miami, Florida, United States
  • Idaho
    • Boise, Idaho, United States
  • Kansas
    • Wichita, Kansas, United States
  • Kentucky
    • Bardstown, Kentucky, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Minnesota
    • Saint Paul, Minnesota, United States
  • Missouri
    • Kansas City, Missouri, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • North Carolina
    • Cary, North Carolina, United States
    • Raleigh, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Tennessee
    • Knoxville, Tennessee, United States
  • Texas
    • Austin, Texas, United States
    • Houston, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant must be in stable health. Participants may have underlying illnesses such as hypertension, diabetes, ischemic heart disease, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms/signs are medically controlled. If they are on medication for a condition, the medication dose must have been stable for at least 12 weeks preceding vaccination and is expected to remain stable for the duration of the study
• Participant must meet the protocol defined laboratory criteria within 12 days before Day 1
• Participant must be able to attend all scheduled visits and to comply with all study procedures
• Participant must have a body mass index (BMI) of less than or equal to (<=) 35 kilogram per square meter (kg/m^2)
• A woman of childbearing potential must have a negative urine pregnancy test on Day 1 before vaccination

Exclusion Criteria:

• Participant is a woman who is pregnant, breast-feeding, or has a positive urine pregnancy test on Day 1 before vaccination, or is planning to become pregnant 3 months after study vaccine administration or within 3 months after study vaccine administration, or subject is a man who plans to father a child while enrolled in this study or within 3 months after study vaccine administration
• Participant has an acute illness, acute infection, or fever (body temperature greater than or equal to [>=] 38 degree Celsius)
• Participant has a serious chronic disorder, including severe chronic obstructive pulmonary disease or clinically significant congestive heart failure, requirement for supplemental oxygen, end stage renal disease with or without dialysis, clinically unstable cardiac disease, or has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (example compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
• Participant has a history of neoplastic disease (excluding non-melanoma skin cancer that was successfully treated) within the past 5 years or a history of any hematological malignancy
• Participant has known or suspected congenital or acquired immunodeficiency (including leukemia, HIV seropositivity), has received immunosuppressive therapy (such as anti-cancer chemotherapy, radiation therapy or cytotoxic drugs), within the preceding 6 months; or long-term systemic corticosteroid therapy [prednisone or equivalent for more than 2 consecutive weeks within the past 3 months]), or has chronic active hepatitis B or hepatitis C infection, documented by hepatitis B surface antigen and hepatitis C antibody, respectively

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ExPEC4V (4 : 4 : 4 : 4); Participants will be stratified according to their age in 2 groups >=18 to <50 years and >=50 years. Part 1: In age group >= 18 to <50 years, participants will receive single vaccination of ExPEC4V dose (4 : 4 : 4 : 4) as an intramuscular (i.m) injection into deltoid muscle. The ExPEC4V doses contain polysaccharide antigen (in microgram [mcg]) from the ExPEC serotypes O1A, O2, O6A, and O25B. Participants in >=50 years group will be enrolled in stepwise,dose-escalating procedure. In step 1, lowest dose of ExPEC4V (4:4:4:4) or Placebo will be given, in step 2 either of 2 medium doses of ExPEC4V or placebo and in step 3, either of 2 highest doses of ExPEC4V or placebo. Participants will be enrolled into subsequent steps only if vaccination in previous steps is deemed safe based on review of safety data by the IDMC. Participants will be enrolled into Part 2 only if vaccination in Part 1 is deemed safe based on the review of safety data through Day 8 by the IDMC.	Biological: ExPEC4V (4 : 4 : 4 : 4); Participants will receive single vaccination of ExPEC4V dose (4 : 4 : 4 : 4) as an intramuscular (i.m) injection into deltoid muscle in part 1 (age groups >=18 to <50 years and >=50 years) and part 2 (based on review of safety data by the IDMC). The ExPEC4V doses contain polysaccharide antigen (in microgram [mcg]) from the ExPEC serotypes O1A, O2, O6A, and O25B.; Other Names: JNJ-63871860; Drug: Placebo; Participants will receive matching placebo (Tris-buffered saline) to ExPEC4V.
Experimental: ExPEC4V (4 : 4 : 4 : 8); Participants will be stratified according to their age in 2 groups >=18 to <50 years and >=50 years. Part 1: In age group >= 18 to <50 years, participants will receive single vaccination of ExPEC4V dose (4 : 4 : 4 : 8) as an i.m injection into deltoid muscle. The ExPEC4V doses contain polysaccharide antigen (in mcg) from the ExPEC serotypes O1A, O2, O6A, and O25B. Participants in >=50 years group will be enrolled in stepwise,dose-escalating procedure. In step 1, lowest dose of ExPEC4V or Placebo will be given, in step 2 either of 2 medium doses (4 : 4 : 4 : 8/8 : 8 : 8 : 8) of ExPEC4V or placebo and in step 3, either of 2 highest doses of ExPEC4V or placebo. Participants will be enrolled into subsequent steps only if vaccination in previous steps is deemed safe based on review of safety data by the IDMC. Participants will be enrolled into Part 2 only if vaccination in Part 1 is deemed safe based on the review of safety data through Day 8 by the IDMC.	Drug: Placebo; Participants will receive matching placebo (Tris-buffered saline) to ExPEC4V.; Biological: ExPEC4V (4 : 4 : 4 : 8); Participants will receive single vaccination of ExPEC4V dose (4 : 4 : 4 : 8) as an i.m injection into deltoid muscle in part 1 (age groups >=18 to <50 years and >=50 years) and part 2 (based on review of safety data by the IDMC). The ExPEC4V doses contain polysaccharide antigen (in mcg) from the ExPEC serotypes O1A, O2, O6A, and O25B.; Other Names: JNJ-63871860
Experimental: ExPEC4V (8 : 8 : 8 : 8); Participants will be stratified according to their age in 2 groups >=18 to <50 years and >=50 years. Part 1: In age group >= 18 to <50 years, participants will receive single vaccination of ExPEC4V dose (8 : 8 : 8 : 8) as an i.m injection into deltoid muscle. The ExPEC4V doses contain polysaccharide antigen (in mcg) from the ExPEC serotypes O1A, O2, O6A, and O25B. Participants in >=50 years group will be enrolled in stepwise,dose-escalating procedure. In step 1, lowest dose of ExPEC4V or Placebo will be given, in step 2 either of 2 medium doses (4 : 4 : 4 : 8/8 : 8 : 8 : 8) of ExPEC4V or placebo and in step 3, either of 2 highest doses of ExPEC4V or placebo. Participants will be enrolled into subsequent steps only if vaccination in previous steps is deemed safe based on review of safety data by the IDMC. Participants will be enrolled into Part 2 only if vaccination in Part 1 is deemed safe based on the review of safety data through Day 8 by the IDMC.	Drug: Placebo; Participants will receive matching placebo (Tris-buffered saline) to ExPEC4V.; Biological: ExPEC4V (8 : 8 : 8 : 8); Participants will receive single vaccination of ExPEC4V dose (8 : 8 : 8 : 8) as an i.m injection into deltoid muscle in part 1 (age groups >=18 to <50 years and >=50 years) and part 2 (based on review of safety data by the IDMC). The ExPEC4V doses contain polysaccharide antigen (in mcg) from the ExPEC serotypes O1A, O2, O6A, and O25B.; Other Names: JNJ-63871860
Experimental: ExPEC4V (8 : 8 : 8 : 16); Participants will be stratified according to their age in 2 groups >=18 to <50 years and >=50 years. Part 1: In age group >= 18 to <50 years, participants will receive single vaccination of ExPEC4V dose (8 : 8 : 8 : 16) as an i.m injection into deltoid muscle. The ExPEC4V doses contain polysaccharide antigen (in mcg) from the ExPEC serotypes O1A, O2, O6A, and O25B. Participants in >=50 years group will be enrolled in stepwise,dose-escalating procedure. In step 1, lowest dose of ExPEC4V or Placebo will be given, in step 2 either of 2 medium doses of ExPEC4V or placebo and in step 3, either of 2 highest doses (8 : 8 : 8 : 16/16 : 16 : 16 : 16) of ExPEC4V or placebo. Participants will be enrolled into subsequent steps only if vaccination in previous steps is deemed safe based on review of safety data by the IDMC. Participants will be enrolled into Part 2 only if vaccination in Part 1 is deemed safe based on the review of safety data through Day 8 by the IDMC.	Drug: Placebo; Participants will receive matching placebo (Tris-buffered saline) to ExPEC4V.; Biological: ExPEC4V (8 : 8 : 8 : 16); Participants will receive single vaccination of ExPEC4V dose (8 : 8 : 8 : 16) as an i.m injection into deltoid muscle in part 1 (age groups >=18 to <50 years and >=50 years) and part 2 (based on review of safety data by the IDMC). The ExPEC4V doses contain polysaccharide antigen (in mcg) from the ExPEC serotypes O1A, O2, O6A, and O25B.; Other Names: JNJ-63871860
Experimental: ExPEC4V (16 : 16 : 16 : 16); Participants will be stratified according to their age in 2 groups >=18 to <50 years and >=50 years. Part 1: In age group >= 18 to <50 years, participants will receive single vaccination of ExPEC4V dose (16 : 16 : 16 : 16) as an i.m injection into deltoid muscle. The ExPEC4V doses contain polysaccharide antigen (in mcg) from the ExPEC serotypes O1A, O2, O6A, and O25B. Participants in >=50 years group will be enrolled in stepwise,dose-escalating procedure. In step 1, lowest dose of ExPEC4V or Placebo will be given, in step 2 either of 2 medium doses of ExPEC4V or placebo and in step 3, either of 2 highest doses (8 : 8 : 8 : 16/16 : 16 : 16 : 16) of ExPEC4V or placebo. Participants will be enrolled into subsequent steps only if vaccination in previous steps is deemed safe based on review of safety data by the IDMC. Participants will be enrolled into Part 2 only if vaccination in Part 1 is deemed safe based on the review of safety data through Day 8 by the IDMC.	Drug: Placebo; Participants will receive matching placebo (Tris-buffered saline) to ExPEC4V.; Biological: ExPEC4V (16 : 16 : 16 : 16); Participants will receive single vaccination of ExPEC4V dose (16 : 16 : 16 : 16) as an i.m injection into deltoid muscle in part 1 (age groups >=18 to <50 years and >=50 years) and part 2 (based on review of safety data by the IDMC). The ExPEC4V doses contain polysaccharide antigen (in mcg) from the ExPEC serotypes O1A, O2, O6A, and O25B.; Other Names: JNJ-63871860
Placebo Comparator: Placebo; Participants will be stratified according to their age in 2 groups >= 18 to <50 years and >=50 years. Part 1: Participants will receive matching placebo to ExPEC4V as an intramuscular injection into the deltoid muscle. Participants will be enrolled into Part 2 only if vaccination in Part 1 is deemed safe and well tolerated based on the review of safety data through Day 8 by the IDMC.	Drug: Placebo; Participants will receive matching placebo (Tris-buffered saline) to ExPEC4V.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Solicited Local Adverse Events (AEs)	Solicited AEs are precisely defined events that participants are specifically asked about and which are noted by participants through the electronic Subject Diary. Solicited Local AEs: Participants will be instructed on how to note occurrences of pain/tenderness, erythema, and induration/swelling at the injection site daily for 8 days postvaccination (day of vaccination and the subsequent 7 days) in the electronic Subject Diary. Participants will be instructed on how to measure (using the ruler supplied) and record erythema and induration.	up to Day 8
Number of Participants with Solicited Systemic AEs	Solicited AEs are precisely defined events that participants are specifically asked about and which are noted by participants through the electronic Subject Diary. Solicited Systemic AEs: Participants will be instructed on how to note daily symptoms in the electronic Subject Diary for 8 days post vaccination (day of vaccination and the subsequent 7 days) of the following systemic events: fever, headache, fatigue, malaise, nausea, and myalgia.	up to Day 8
Number of Participants with Unsolicited AEs		Up to Day 30
Number of Participants with Serious Adverse Events (SAE's)	An SAE is any adverse event 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 and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.	Until 360 days post vaccination
Dose-dependent Immunogenicity of ExPEC4V on Day 15 (ELISA)	Dose-dependent immunogenicity will be measured by enzyme-linked immunosorbent assay (ELISA) on day 15 in participants with >=18 years of age. Immunoglobulin G (IgG) antibody levels elicited by the vaccine will be measured by ELISA.	Day 15
Long-Term Immunogenicity of ExPEC4V Dose Selected for Further Clinical Development (ELISA)	Evaluation of the immunogenicity of a single vaccination with the ExPEC4V dose selected for further clinical development based on the primary analysis, as measured by ELISA.	Year 2 and 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-dependent Immunogenicity of ExPEC4V on Day 15 (Opsonophagocytic Killing [OPK] Assay)	Dose-dependent immunogenicity will be measured by opsonophagocytic killing (OPK) assay on day 15 in participants with >=18 years of age. Specific functional antibacterial antibodies will be measured by OPK.	Day 15
Correlation Between ELISA (total antibody) and OPK (functional antibody) Serum Titers		Day 15
Dose-dependent Immunogenicity of ExPEC4V on Day 30 (ELISA)	Dose-dependent immunogenicity will be measured by ELISA on day 30 in participants with >=18 years of age. IgG antibody levels elicited by the vaccine will be measured by ELISA.	Day 30
Immunogenicity of ExPEC4V Dose Selected for Further Clinical Development (ELISA)	The immunogenicity of the ExPEC4V dose selected for further clinical development based on the interim analysis, as measured by ELISA will be evaluated. IgG antibody levels elicited by the vaccine will be measured by ELISA.	Day 180 and 360
Immunogenicity of ExPEC4V Dose Selected for Further Clinical Development (OPK)	The immunogenicity of the ExPEC4V dose selected for further clinical development based on the interim analysis, as measured by OPK assay will be evaluated. Specific functional antibacterial antibodies will be measured by OPK.	Days 30, 180, and 360

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Frenck RW Jr, Ervin J, Chu L, Abbanat D, Spiessens B, Go O, Haazen W, van den Dobbelsteen G, Poolman J, Thoelen S, Ibarra de Palacios P. Safety and immunogenicity of a vaccine for extra-intestinal pathogenic Escherichia coli (ESTELLA): a phase 2 randomised controlled trial. Lancet Infect Dis. 2019 Jun;19(6):631-640. doi: 10.1016/S1473-3099(18)30803-X. Epub 2019 May 9.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2015
• Primary Completion (Actual): September 12, 2016
• Study Completion (Actual): June 21, 2019

Study Registration Dates

• First Submitted: September 9, 2015
• First Submitted That Met QC Criteria: September 9, 2015
• First Posted (Estimate): September 11, 2015

Study Record Updates

• Last Update Posted (Actual): April 22, 2020
• Last Update Submitted That Met QC Criteria: April 16, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Healthy; JNJ-63871860; ExPEC4V
• Other Study ID Numbers: CR107946; 63871860BAC2001 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No