Mucosal Immunity Against Neisseria Gonorrhoeae After 4CMenB Vaccination

NCT04722003 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 19-0015
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2 mechanistic clinical trial to assess the systemic and mucosal immunogenicity of the multicomponent meningococcal serogroup B vaccine (4CMenB or Bexsero (R)) (group 1, 40 subjects) against Neisseria gonorrhoeae, using a placebo vaccine (normal saline) as a comparator (group 2, 10 subjects). There will be approximately 50 participants, ages 18-49, both male and non-pregnant female subjects, enrolled at 1 site in the US. The goal will be to ensure adequate representation of subjects by sex in both treatment groups. The enrollment will be stratified by both sex and treatment arm. During enrollment of the "biopsy cohort" male and non-pregnant female subjects will be randomized 4:1 to either 4CMenB or placebo, up to a maximum of 10 male and 10 non-pregnant female subjects. Group 1 (approximate N=40) will receive two doses of 4CMenB on Day 1 and Day 29. Group 2 (approximate N=10) will receive two placebo injections on Day 1 and Day 29. Both groups will receive a single-dose prefilled syringe that is administered intramuscularly (0.5-mililiter each). The duration of each subject's participation is approximately 8 months, from recruitment through the last study visit, and the length of the study is estimated for 14 months. The primary objective is to characterize the rectal mucosal Immunoglobulin G IgG antibody response to Neisseria gonorrhoeae (GC) elicited by the 4CMenB vaccine as compared with the placebo vaccine (normal saline) in healthy adult subjects.

Conditions

Gonorrhoea

Keywords

4CMenB; Gonorrhea; Meningococcal Group B Vaccine; Meningococcal Immunization; Mucosal Immune Response; Neisseria gonorrhoeae

Outcome Measures

Primary Outcomes (2)

• Rectal Mucosal IgG Concentrations (Geometric Mean Titers [GMT]) Against N. Gonorrhoeae Outer Membrane Vesicle (OMV) Antigen Ng1291

  Rectal mucosal IgG concentrations (geometric mean titers, GMT) against GC OMV antigen Ng1291 by ELISA at Day 1, 29, 43, 57, and 181 in each treatment group

  Day 1 through Day 181

• Rectal Mucosal IgG Concentrations (Geometric Mean Titers [GMT]) Against N. Gonorrhoeae Outer Membrane Vesicle (OMV) Antigen CNG20

  Rectal mucosal IgG concentrations (geometric mean titers, GMT) against GC OMV antigen CNG20 by ELISA at Day 1, 29, 43, 57, and 181 in each treatment group

  Day 1 through day 181

Secondary Outcomes (4)

• Serum IgG Concentrations (Geometric Mean Titers [GMT]) Against N. Gonorrhoeae Outer Membrane Vesicle (OMV) Antigen Ng1291

  Day 1 through Day 181

• Serum IgG Concentrations (Geometric Mean Titers [GMT]) Against N. Gonorrhoeae Outer Membrane Vesicle (OMV) Antigen CNG20

  Day 1 through day 181

• The Reactogenicity of 4CMenB in Healthy Adult Participants

  Day 1 through Day 181

• Frequency of Serious Adverse Events (SAE)

  Day 1 through Day 181

Study Arms (2)

4CMenB

EXPERIMENTAL

Participants will receive two doses (0.5 mL each) of 4CMenB vaccine on Day 1 and Day 29. Each single dose of vaccine will be administered via intramuscular (IM) injection into the deltoid muscle of the preferred arm. N=40

Biological: Meningococcal Group B Vaccine

Placebo

PLACEBO COMPARATOR

Participants will receive two doses (0.5 mL each) of placebo injections (saline) on Day 1 and Day 29. Each single dose of placebo will be administered via intramuscular (IM) injection into the deltoid muscle of the preferred arm. N=10

Other: Placebo

Interventions

Meningococcal Group B Vaccine BIOLOGICAL

A combination vaccine consisting of recombinant proteins Neisserial adhesin A (NadA), Neisserial Heparin Binding Antigen (NHBA), and factor H binding protein (fHbp), Outer Membrane Vesicles (OMV), aluminum hydroxide, sodium chloride, histidine, and sucrose.

4CMenB

Placebo OTHER

0.9% Sodium Chloride, USP injection.

Placebo

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must be aged 18-49 years old (inclusive) at the time of vaccination.
• Must be able to provide written informed consent.
• Must have a body mass index (BMI) \>/= 18.5 and \< 35.0 kg/m2
• Must be in good health based on physical examination, vital signs\*, medical history, safety labs\*\* (as applicable to the rectal biopsy and no biopsy cohorts) and the investigator's clinical judgment.
• \*Vital signs must be within the normal ranges. If a subject has elevated systolic or diastolic blood pressure, subject may rest for 10 minutes in a quiet room and the blood pressure may be retaken.
• \*\*Safety labs must be within the normal ranges and the normal ranges will be those used by the reference clinical lab.
• For female subjects only: If a female participant is of childbearing potential\*, she must use contraception\*\* from 30 days before study product administration through the end of study participation.
• \*A woman is considered of childbearing potential unless post-menopausal (defined as history of \>/= 1 year of spontaneous amenorrhea), or permanently surgically sterilized (bilateral oophorectomy, salpingectomy, hysterectomy).
• \*\*Acceptable methods of contraception include: abstinence or no sex with a male, monogamous relationship with a man who had a vasectomy at least 6 months before the 1st study vaccine, prescription oral contraceptives, intrauterine device (IUD), birth control implants or injections, contraceptive patch, vaginal ring, condoms and diaphragms/cervical cap with spermicide ("double barrier" method).
• Must be available and willing to participate for the duration of this trial.
• Willing to provide mucosal samples: vaginal secretions for women and oropharyngeal and rectal secretions for men and women.
• For the rectal biopsy cohort only, willing to provide rectal biopsies.

You may not qualify if:

• Has ever been diagnosed with meningococcal infection or gonococcal infection at any anatomic site.
• Has ever received any serogroup B meningococcal vaccine.
• Any positive test result for STI (including Neisseria gonorrhoeae (GC) Chlamydia trachomatis (CT), Rapid Plasma Reagin (RPR) and Human Immunodeficiency Virus (HIV)) at screening\*.
• \*Female subjects will also be tested for Trichomonas at screening.
• Any history of Chlamydia trachomatis or syphilis infection at any body site in the preceding 12 months
• Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products.
• Has severe allergy or anaphylaxis to latex.
• Has an acute illness or temperature \>/= 38.0 degrees Celsius on Day 1\*.
• \*Subjects with fever or acute illness on the day of vaccination may be re-assessed and enrolled if healthy or only minor residual symptoms remain within 3 days.
• Has a history of a bleeding disorder, or is taking chronic anti-coagulant (e.g. warfarin, direct thrombin inhibitors, heparin products, etc.), anti-platelet, or non-steroidal anti-inflammatory drugs (NSAID) therapy.
• Has history of autoimmune disease, or clinically significant cardiac, pulmonary, gastrointestinal, hepatic, rheumatologic, or renal disease by history or physical examination.
• Has history of active malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure\*.
• \*Subjects with a history of skin cancer must not be vaccinated at the previous tumor site.
• Has known or suspected congenital or acquired immunodeficiency, or recent history or current use of immunosuppressive therapy\*.
• \*Anti-cancer chemotherapy or radiation therapy within the preceding 3 years, or long-term (\>/= 2 weeks within the previous 3 months) systemic corticosteroid therapy (at a dosage of \>/= 0.5 mg/kg/day). Intranasal or topical prednisone (or equivalent) are allowed.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

The Hope Clinic of Emory University

Decatur, Georgia, 30030-1705, United States

Location

MeSH Terms

Conditions

Gonorrhea

Interventions

4CMenB vaccine

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Results Point of Contact

• Title: Varun K. Phadke, MD
• Organization: Emory University Vaccine and Treatment Evaluation Unit (VTEU)

varun.phadke@emory.edu

404-712-9046

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2021
• First Posted: January 25, 2021
• Study Start: November 1, 2021
• Primary Completion: October 2, 2023
• Study Completion: October 2, 2023
• Last Updated: November 5, 2024
• Results First Posted: November 5, 2024

Record last verified: 2020-12-11

Locations

US (1)