Investigating the Immunogenicity of a U.S.-Licensed Meningococcal Serogroup B Vaccine (Trumenba)

NCT ID: NCT02569632

Last Updated: 2021-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2016-12-31

Brief Summary

This study will investigate the breadth of protection against meningococcal disease in humans immunized with a newly FDA approved meningococcal B vaccine, trade name "Trumenba®" manufactured by Pfizer Vaccines. As a secondary goal the investigators will investigate underlying mechanisms by which human anti-FHbp antibodies elicit complement-mediated bactericidal activity.

Detailed Description

Neisseria meningitidis causes meningitis and severe infections of the blood stream. The incidence of serogroup B meningococcal disease however is too low to conduct a randomized, controlled trial to determine the actual efficacy of the new serogroup B vaccines. Instead vaccine efficacy was inferred from serum bactericidal antibody responses using four test strains. However, because of strain variability of FHbp amino acid sequence (there are more than 800 sequence variants described) and strain variability of FHbp expression, bactericidal data on only four strains are unlikely to be sufficient to predict the actual strain coverage by the vaccine. There also are gaps in knowledge about the underlying mechanisms by which human antibodies to FHbp elicit complement mediated bactericidal activity. For example, binding of FH to FHbp is specific for human FH. Therefore in vaccinated humans the vaccine antigen is expected to form a complex with FH right after immunization. The investigators' hypothesis is that binding of human FH to the vaccine antigen skews the antibody repertoire to FHbp epitopes located outside of the FH combining site. The resulting antibodies would be expected not to inhibit binding of FH to the bacteria. This hypothesis will be investigated in Trumenba-immunized humans as part of studies in Aim 1 (and in future studies of recombinant human anti-FHbp Fabs that will be enabled by obtaining DNA from individual B cells, described in Aim 2).

Conditions

Meningococcal Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Open Label: MenB-FHbp

Trumenba Meningococcal Group B Vaccine (Wyeth/Pfizer Pharmaceuticals)

Group Type: EXPERIMENTAL

Trumenba Vaccine (Wyeth/Pfizer Pharmaceuticals)

Intervention Type: BIOLOGICAL

All subjects will receive three doses of a Trumenba, a U.S.-licensed meningococcal vaccine. Each 0.5 mL dose contains 60 micrograms of each FHbp variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al³+ as AlPO4 in 10 mM histidine buffered saline at pH 6.0. Trumenba is administered as a three dose series (0.5 mL each) according to a 0-, 2-, and 6-month schedule.

Interventions

Trumenba Vaccine (Wyeth/Pfizer Pharmaceuticals)

All subjects will receive three doses of a Trumenba, a U.S.-licensed meningococcal vaccine. Each 0.5 mL dose contains 60 micrograms of each FHbp variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al³+ as AlPO4 in 10 mM histidine buffered saline at pH 6.0. Trumenba is administered as a three dose series (0.5 mL each) according to a 0-, 2-, and 6-month schedule.

Intervention Type: BIOLOGICAL

Other Intervention Names

MenB-FHbp

Eligibility Criteria

Inclusion Criteria

• Adults in the following risk groups: physicians, nurses, respiratory therapists, microbiology laboratory personnel working at UCSF Benioff Children's Hospital Oakland or the University of Massachusetts Medical School as well as medical students attending accredited U.S. medical schools
• Able to comprehend and follow all required study procedures
• In good health as determined by a brief medical history
• For females of child bearing age a negative urine pregnancy test will be required

Exclusion Criteria

• Are not in the risk groups summarized above
• Have not given or are unable to give written informed consent to participate in the study
• Females of child bearing potential who are pregnant, or planning on becoming pregnant during the study period.
• Persons with a past history of having Guillain-Barré Syndrome (GBS), or a family history of GBS in a parent or sibling.
• Persons with presence or suspected presence of serious chronic disease including but not limited to: chronic cardiac disease, autoimmune disease, diabetes, hepatitis B/C, HIV, progressive neurological disease or seizure, leukemia, lymphomas, or neoplasm.
• Have participated in any other investigational drug or received any other vaccine within the last 30 days.
• Received a dose of a meningococcal serogroups A, C, Y, W conjugate vaccine within the previous 30 days or wish to receive a dose of this vaccine during the six month study period.
• Have a history of anaphylactic shock, asthma, urticaria or other allergic reaction after previous dose of Trumenba
• Have experienced fever (oral temperature above 38.0°C) within the past 3 days or are suffering from a present acute infectious disease
• Are planning to leave the area of the study site before the end of the study period
• Have obesity (BMI higher than 33); or 11.
• With any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Massachusetts, Worcester

OTHER

Sponsor Role: collaborator

UCSF Benioff Children's Hospital Oakland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dan Granoff, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Oakland Research Institute, Center for Immunobiology and Vaccine Development

Locations

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Countries

United States

References

Lujan E, Partridge E, Giuntini S, Ram S, Granoff DM. Breadth and Duration of Meningococcal Serum Bactericidal Activity in Health Care Workers and Microbiologists Immunized with the MenB-FHbp Vaccine. Clin Vaccine Immunol. 2017 Aug 4;24(8):e00121-17. doi: 10.1128/CVI.00121-17. Print 2017 Aug.

Reference Type: RESULT

PMID: 28566335 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

ChildrensHRCOakland

Identifier Type: -

Identifier Source: org_study_id