Study to Assess Gonorrhoeae Immune Responses Induced by a N. Meningitidis Vaccine (4CMenB)

Institute for Global Health and Infectious Diseases (IGHID) 11911 - Cross-reactive N. Gonorrhoeae Immune Responses Induced by a N. Meningitidis Vaccine

The purpose of this study is to test whether the group B meningitis vaccine (brand name Bexsero™) induces immune responses against the bacteria that causes gonorrhea.

Participants: Approximately 15 Individuals who are 18-25 years of age that are not pregnant, HIV negative, have no history of congenital immunologic disorder, and are not taking immune suppressive medications will be enrolled on this study at a single site, University of North Carolina at Chapel Hill (UNC-CH).

Procedures (methods): Participants will receive two-doses of an FDA-approved vaccine that provides protection from N. meningitidis infection according to the recommended dosing schedule. The first vaccine dose will be given to participants at the entry visit and the second vaccine dose will be given to participants at the week 5 visit. The participants will provide samples of blood as well as mucosal surface derived samples (urine and/or swabs) at four separate visits (entry, week 5, week 6, and week 7).

Study Overview

• Status: Completed
• Conditions: Neisseria Gonorrhoeae Infection
• Intervention / Treatment: Biological: Meningococcal Group B Vaccine

Detailed Description

This study is a single center, single arm, interventional pilot study in which participants will receive two-doses of the 4CMenB vaccine according to the recommended administration schedule and will provide blood, pharyngeal swabs, and urine or self-collected vaginal swabs at each of four study visits.

The study population will include 15 individuals aged 18-25 years with no contraindication to vaccination and no known immune compromising medical condition or medication.

Participants will be seen for informed consent and eligibility screening. Enrolled participants will be given 1 dose of 4CMenB at enrollment and a second dose at week 5. Participants will be seen at entry, weeks 5, 6, and 7 for blood collection, pharyngeal swabs, and provide urine (male participants) or self-collected vaginal swabs collected for secondary screening and baseline immunologic testing.

Screening Evaluations Screening evaluations include: medical history, medication history within the past 60 days, vital signs, targeted physical exam, and pregnancy test for female participants of child bearing potential). Screening visit must be conducted no greater than 30 days prior to enrollment visit. The screening evaluation and enrollment visit can all occur on the same day. Participants may be re-screened one time.

Entry Evaluations

Entry evaluations will be collected PRIOR to phlebotomy, specimen collection, and vaccine administration:

Acute Illness Assessment will be completed before phlebotomy, specimen collection, and vaccine administration. Participants who have an acute illness may be rescheduled for their phlebotomy, specimen collection, and vaccine within their screening visit window.

Update medical history and concomitant medications. Conduct a targeted physical exam and collect vital signs [heart rate (HR), blood pressure (BP), oral temperature (Temp), respiration rate (RR), and weight] prior to phlebotomy to collect up to 60 mL of blood, specimen collection, and vaccine administration.

For females of reproductive potential, negative urine pregnancy testing results must be available before phlebotomy, specimen collection, and vaccine administration.

Samples to be stored for immunologic testing will be batch run at the end of the study:

pharyngeal swabs, urine sample (from male participants), self-collected vaginal swabs (from female participants), serum, and peripheral blood mononuclear cells (PBMC).

Post-Entry Evaluations

Week 5 Evaluations:

Acute Illness Assessment will be completed before phlebotomy, specimen collection, and vaccine administration. Participants who have an acute illness or who have taken exclusionary anticoagulant medications may be rescheduled for their vaccine within their screening visit window.

Update medical history and concomitant medications before phlebotomy and vaccine administration. Conduct a targeted physical exam and collect vital signs (HR, BP, Temp, RR) before phlebotomy to collect up to 60 mL of blood, specimen collection, and vaccine administration.

For females of reproductive potential, negative urine pregnancy testing results must be available before phlebotomy, specimen collection, and vaccine administration.

Week 5 laboratory evaluations will be collected PRIOR to vaccine administration:

Samples to be stored for immunologic testing will be batch run at the end of the study:

pharyngeal swabs, urine sample (from male participants), self-collected vaginal swabs (from female participants), serum, and PBMC.

Week 6 and Week 7 Evaluations:

Update medical history and concomitant medications prior to phlebotomy to collect up to 60 mL of blood and specimen collection.

Samples to be stored for immunologic testing will be batch run at the end of the study:

pharyngeal swabs, urine sample (from male participants), self-collected vaginal swabs (from female participants), serum, and PBMC.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 21 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able to understand and give informed consent
2. Willingness to undergo all study procedures.
3. Males or females between the ages of 18 to 25 at screening (inclusive).
4. Good health, as determined by medical history and targeted physical exam.
5. Participants agree to abstain from vaccines from study entry to 30 days after receipt of the second 4CMenB vaccine.
6. Female participants of child bearing potential must have a negative urine pregnancy test at the screening visit, and prior to receipt of vaccines at study entry and week 5 visits. Self-reported history is acceptable documentation of hysterectomy, bilateral oophorectomy, tubal ligation, or tubal micro-inserts which eliminate child bearing potential of participant. If participating in sexual activity that could lead to pregnancy, women must agree to use a form of contraceptive until 28 days after completion of the vaccine series. At least one of the following methods must be used appropriately: Condoms (male) with or without spermicidal agent, Diaphragm or cervical cap with spermicide, Intrauterine device (IUD), or Hormone-based contraceptive. Self-report of a monogamous male partner who has a vasectomy is also acceptable.

Exclusion Criteria:

1. Known allergy/sensitivity or any hypersensitivity to latex or any of the components of the study product or its formulation (see section 5.2 for a list of components).
2. Participants who have received any vaccine directed against N. meningitidis serogroup B
3. Serious illness or injury requiring hospitalization within 21 days prior to study entry.
4. Current or prior history of a medical condition resulting in impaired immunity (such as HIV infection, inborn or acquired immunodeficiency syndromes, all cancers including leukemia or lymphoma, or the of use antineoplastic drugs or radiation treatment).
5. Known active infection with HIV, Hepatitis C Virus (HCV ), or Hepatitis B Virus (HBV). This information will be obtained verbally from the participant.
6. History of excessive alcohol consumption, drug abuse, psychiatric conditions, social conditions or occupational conditions that in the opinion of the investigator would preclude compliance with the study.
7. Hemophilia or other bleeding diatheses.
8. Receipt of anticoagulants (aspirin or nonsteroidal anti-inflammatory drugs (NSAIDS) are acceptable) within 14 days prior to study entry.
9. Autoimmune disorders; mild autoimmune disorders, such as eczema, are not exclusionary and will be determined by the investigator.
10. Use of any systemic immunomodulatory treatment, systemic corticosteroids, (inhaled and topical corticosteroids acceptable), investigational products, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry.
11. Pregnant women and nursing mothers or women who are planning to become pregnant or breastfeed within 28 days after receipt of their second 4CMenB vaccine.
12. Have received any licensed vaccine within 30 days prior to study vaccination.
13. Have donated blood or blood products within 30 days before study vaccination, plan to donate blood at any time during the study and up to 30 days after the last blood draw.
14. Any condition in the opinion of the investigator that would interfere with the proper conduct of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4CMenB Vaccine; Participants will receive the 4CMenB (Bexsero) vaccine by an injection in the deltoid region of the upper arm or the higher front area on one side of the thigh at the enrollment visit (Day 0) and at week 5.	Biological: Meningococcal Group B Vaccine; All participants will receive the 4CMenB vaccine, 0.5 mL, at entry (Day 0) and at week 5.; Other Names: Bexsero; 4-component Neisseria meningitidis group B vaccine; 4CMenB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Anti-N. Gonorrhoeae Outer-membrane Vesicle Specific Immunoglobulin G (IgG) Concentrations After Immunization	The change in concentrations presented as the difference in geometric mean concentration in human serum of IgG binding to N. gonorrhoeae strain FA1090 surface antigens Outer-membrane vesicles (OMV) determined by ELISA in serum from entry visit and week 7 visit	pre-vaccination at entry visit (prior to first vaccination, Day 0) and week 7 visit (2 weeks after second vaccination)
Change in Anti-N. Gonorrhoeae Outer-membrane Vesicle Specific Immunoglobulin M (IgM) Concentrations After Immunization	The change in concentrations presented as the difference in geometric mean concentration in human serum of IgM binding to N. gonorrhoeae strain FA1090 surface antigens (Outer-membrane vesicles) determined by ELISA in serum from entry visit and week 7 visit	pre-vaccination at entry visit (prior to first vaccination, Day 0) and week 7 visit (2 weeks after second vaccination)
Change in Anti-N. Gonorrhoeae Outer-membrane Vesicle Specific Immunoglobulin A (IgA ) Concentrations After Immunization	The change in concentrations presented as the difference in geometric mean concentration in human serum of IgA binding to N. gonorrhoeae strain FA1090 surface antigens (Outer-membrane vesicles) determined by ELISA in serum from entry visit and week 7 visit	pre-vaccination at entry visit (prior to first vaccination, Day 0) and week 7 visit (2 weeks after second vaccination)
Mean Change in Proportion of Cluster of Differentiation 4 Positive (CD4+) T Cells Expressing at Least Two Different Activation Markers After Immunization	Flow cytometry used to measure the number of CD4+ lymphocytes expressing Interferon-gamma (IFN-g), Tumor Necrosis Factor-alpha (TNF-a), Interleukin-2 (IL-2), and Cluster of Differentiation 107a (CD107a) after in vitro stimulation with N. gonorrhoeae strain FA1090 Outer-membrane vesicles in circulating peripheral blood mononuclear cells (PBMC). The frequency of CD4+ T cells expressing at least two activation markers will be expressed as a proportion of total CD4+ lymphocytes. The change in frequency will be presented as the difference between frequency of cells measured at entry visit and at week 7 visit.	pre-vaccination at entry visit (prior to first vaccination, Day 0) and week 7 visit (2 weeks after second vaccination)

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: North Carolina Translational and Clinical Sciences Institute
• Investigators: Principal Investigator: Joseph A Duncan, MD, PhD, UNC-Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2019
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: September 16, 2019
• First Submitted That Met QC Criteria: September 16, 2019
• First Posted (Actual): September 19, 2019

Study Record Updates

• Last Update Posted (Actual): July 15, 2021
• Last Update Submitted That Met QC Criteria: June 24, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Vaccine; Immune; Neisseria meningitidis; Neisseria gonorrhoeae; Cross-reactive; Responses
• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Sexually Transmitted Diseases, Bacterial; Gonorrhea; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 19-1145

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual data that supports the results will be shared beginning 12 to 24 months following publication provided the investigator/researcher who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: 12-24 months after publication
• IPD Sharing Access Criteria: Other investigators/researchers who propose to use the individual participant data (IPD) from this study will need to have approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and execute a data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No