Safety, Tolerability and Immunogenicity of 4CMenB Vaccine(2 Doses) in Adults With an Immunodeficiency

NCT04295733 | Completed

• 1 other identifier: 4CMenB
• Study Type: observational
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

The meningococcal quadrivalent conjugate vaccine (MenACWY) and the licenced multicomponent MenB vaccine (Bexsero®) have already been included in the Italian childhood immunization programme and recommendations for high risk categories have been also implemented. As by NIP, vaccination against MenB with either 4CMenB or fHbp-MenB is offered for free for several conditions including subjects with severe primary or secondary immunodeficiency. In Liguria Region meningococcal vaccination is actively offered to several chronic conditions including asplenia, patients with lymphoproliferative disease (also HSCT), subject treated with anti-CD20 mAb and HIV-positive. In Liguria Region there is a large diverse population with risk condition that, as by national and regional recommendation, receive meningococcal vaccination. For some of them, i.e. asplenic and complement deficiencies groups, evidence have been generated through an ad hoc clinical trial, while for other important groups there is clear need of immunogenicity data. In the proposed study, the Investigators plan to administer two doses of MenB vaccine (Bexsero®), 1-2 months apart, to adult patients living in Genoa area and belonging to following categories:

• Bone marrow transplant (HSCT patient)
• HIV positive
• Alfa-CD20 subjects (i.e. Patients candidates for / in treatment with biologic drugs such as Rituximab). Immunogenicity data will be then obtained from sera collected at the day of the first Bexsero dose and one month after the immunization course by Serum Bactericidal Activity (SBA) assay.

Conditions

Acquired Immunodeficiency

Outcome Measures

Primary Outcomes (3)

• hSBA geometries mean titres (GMTs) against relevant MenB strains

  hSBA geometries mean titres (GMTs) against relevant MenB strains

  baseline (Visit 1) and one month after the second vaccination (Visit3).

• 4 fold increase in hSBA against relevant MenB

  The proportion of subjects with at least 4 fold increase in hSBA against relevant MenB strains from baseline to one month after the second vaccination (Visit3)

  Baseline to one month after the second vaccination (Visit3)

• hSBA titres >1:4 against relevant MenB strains at Visit3 (one month after the second vaccination)

  The proportion of subjects with "protective" hSBA titres \>1:4 against relevant MenB strains at Visit3 (one month after the second vaccination).

  One month after the second vaccination (Visit3)

Secondary Outcomes (3)

• Local and systemic AEs

  7 days (including the day of vaccination) after Visits 1 and 2.

• Unsolicited AEs

  7 days (including the day of vaccination) after Visits 1 and 2.

• SAEs and AEs leading to withdrawal and medically attended visits throughout the study period

  An average of 15 months (from the day of first vaccination to the end of the study)

Study Arms (3)

Cohort 1

Hematopoietic Stem Celi Transplant (HSCT) patients

Biological: 4CMenB (Bexsero®) vaccine

Cohort 2

HIV infected subjects

Biological: 4CMenB (Bexsero®) vaccine

Cohort 3

Patients candidates for / in treatment with biological drugs such as monoclonal antibodies anti CD-20 (rituximab or ocrelizumab)

Biological: 4CMenB (Bexsero®) vaccine

Interventions

4CMenB (Bexsero®) vaccine BIOLOGICAL

Participants will receive 2 doses of 4CMenB (Bexsero®) vaccine administered intramuscularly 1-2 months apart

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects aged 18 to 65 years with an acquired immune deficiency, including three study groups: * Cohort l-Hematopoietic Stem Celi Transplant (HSCT) patients * Cohort 2-HIV infected subjects * Cohort 3-patients candidates for / in treatment with biological drugs such as monoclonal antibodies anti CD-20 (rituximab or ocrelizumab)

You may qualify if:

• Males and females 18 through 65 years of age at the time of enrollment who are high risk for IMD, including subjects with documented medical history of any of the following criteria:
• Hematopoietic Stem Celi Transplantation (allogenic or autologous stem celi transplant)
• HIV infection
• candidate for / in treatment (ongoing) with biological drugs such as monoclonal antibodies anti CD- 20 (rituximab or ocrelizumab)
• Written informed consent obtained from the subject (or legal representative).
• Subjects (or legal representative) who are able to comprehend all procedures and to comply with the study requirements

You may not qualify if:

• Subjects not able to understand and to adhere to ali study procedures
• Subjects aged \<18 or \>65 years
• Known or suspected allergy/hypersensitivity to any vaccine component
• History of serious adverse reaction to any vaccine
• Administration of immunoglobulins and/or any blood products within 3 months prior to enrollment or planned administration during the entire study period
• History of any meningococcal group B vaccination or having been diagnosed with meningococcal disease ever before
• Stem celi transplantation within 6 months before the enrollment to the study
• HIV-infected patients with detectable viral load (\>50 copies/mL) and/or CD4 celi count \< 200 cells/mm3 in the last 6 months
• Receipt of any vaccine within 28 (for live vaccines) or 14 (for no-live vaccines) days prior to study vaccination
• Planned vaccination (other than the study vaccination) during the entire study period
• Fever or any acute disease or infection within 3 days prior to vaccination
• Receipt of any antibiotics within 3 days before enrollment
• Coagulation disorder contraindicating intramuscular vaccination Any condition that in the opinion of the investigator would pose a health risk to the subject if enrolled or could interfere with the study procedures
• Current participation to another investigational study or planned enrollment to an investigational during the entire study period
• Planned surgery or hospitalization during the entire study period

Sponsors & Collaborators

• Ospedale Policlinico San Martino: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

U.O.Igiene Ospedale Policlinico San Martino - IRCCS

Genoa, 16132, Italy

Location

Related Publications (10)

• Miller EC, Chase NM, Densen P, Hintermeyer MK, Casper JT, Atkinson JP. Autoantibody stabilization of the classical pathway C3 convertase leading to C3 deficiency and Neisserial sepsis: C4 nephritic factor revisited. Clin Immunol. 2012 Dec;145(3):241-50. doi: 10.1016/j.clim.2012.09.007. Epub 2012 Sep 28.

  PMID: 23117396 BACKGROUND

• Salit IE. Meningococcemia caused by serogroup W135. Association with hypogammaglobulinemia. Arch Intern Med. 1981 Apr;141(5):664-5.

  PMID: 6784688 BACKGROUND

• Miller L, Arakaki L, Ramautar A, Bodach S, Braunstein SL, Kennedy J, Steiner-Sichel L, Ngai S, Shepard C, Weiss D. Elevated risk for invasive meningococcal disease among persons with HIV. Ann Intern Med. 2014 Jan 7;160(1):30-7. doi: 10.7326/0003-4819-160-1-201401070-00731.

  PMID: 24166695 BACKGROUND

• Abio A, Neal KR, Beck CR. An epidemiological review of changes in meningococcal biology during the last 100 years. Pathog Glob Health. 2013 Oct;107(7):373-80. doi: 10.1179/2047773213Y.0000000119. Epub 2013 Dec 19.

  PMID: 24392681 BACKGROUND

• Cohn AC, MacNeil JR, Harrison LH, Hatcher C, Theodore J, Schmidt M, Pondo T, Arnold KE, Baumbach J, Bennett N, Craig AS, Farley M, Gershman K, Petit S, Lynfield R, Reingold A, Schaffner W, Shutt KA, Zell ER, Mayer LW, Clark T, Stephens D, Messonnier NE. Changes in Neisseria meningitidis disease epidemiology in the United States, 1998-2007: implications for prevention of meningococcal disease. Clin Infect Dis. 2010 Jan 15;50(2):184-91. doi: 10.1086/649209.

  PMID: 20001736 BACKGROUND

• Crum-Cianflone N, Sullivan E. Meningococcal Vaccinations. Infect Dis Ther. 2016 Jun;5(2):89-112. doi: 10.1007/s40121-016-0107-0. Epub 2016 Apr 16.

  PMID: 27086142 BACKGROUND

• Conferenza Stato-Regioni il 19 gennaio 2017. Piano Nazionale Prevenzione Vaccinale 2017-2019 (PNPV). Gazzetta Ufficiale del 18 febbraio 2017

  BACKGROUND

• Regione Liguria DGR n. 284 del 07/04/2017. Piano Regionale in Prevenzione Vaccinaleaggiornamento 2017. http://www.alisa.liguria.it/index.php?option=com_docman&task=search_result&ltemi d=323.

  BACKGROUND

• Martinon-Torres F, Bernatowska E, Shcherbina A, Esposito S, Szenborn L, Marti MC, Hughes S, Faust SN, Gonzalez-Granado LI, Yu LM, D'Agostino D, Calabresi M, Toneatto D, Snape MD. Meningococcal B Vaccine Immunogenicity in Children With Defects in Complement and Splenic Function. Pediatrics. 2018 Sep;142(3):e20174250. doi: 10.1542/peds.2017-4250. Epub 2018 Aug 1.

  PMID: 30068713 BACKGROUND

• Ram S, Lewis LA, Rice PA. Infections of people with complement deficiencies and patients who have undergone splenectomy. Clin Microbiol Rev. 2010 Oct;23(4):740-80. doi: 10.1128/CMR.00048-09.

  PMID: 20930072 RESULT

MeSH Terms

Interventions

4CMenB vaccine; Vaccines

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 24, 2020
• First Posted: March 4, 2020
• Study Start: February 6, 2020
• Primary Completion: January 11, 2024
• Study Completion: January 11, 2024
• Last Updated: January 22, 2024

Record last verified: 2024-01

Locations

IT (1)