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

Study Overview
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Brief Summary
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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.

Official Title
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Evaluation of Safety, Tolerability and Immunogenicity of Two Doses of the 4CMenB Vaccine in Adults With an Immunodeficiency

Conditions
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Acquired Immunodeficiency

Intervention / Treatment
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* Biological: 4CMenB (Bexsero®) vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 Subjects who participated in Cohort 1, 2 or 3, cannot be included in other different cohorts Pregnancy or breastfeeding (asking the woman to sign a declaration that she is not pregnant or breastfeeding). Any contraindication to the study vaccine (Bexsero®) as specified in the Summary of Product Characteristics.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>Hematopoietic Stem Celi Transplant (HSCT) patients | Biological: 4CMenB (Bexsero®) vaccine<br>* Participants will receive 2 doses of 4CMenB (Bexsero®) vaccine administered intramuscularly 1-2 months apart<br>|
| Cohort 2<br>HIV infected subjects | Biological: 4CMenB (Bexsero®) vaccine<br>* Participants will receive 2 doses of 4CMenB (Bexsero®) vaccine administered intramuscularly 1-2 months apart<br>|
| Cohort 3<br>Patients candidates for / in treatment with biological drugs such as monoclonal antibodies anti CD-20 (rituximab or ocrelizumab) | Biological: 4CMenB (Bexsero®) vaccine<br>* Participants will receive 2 doses of 4CMenB (Bexsero®) vaccine administered intramuscularly 1-2 months apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local and systemic AEs | The incidence of subjects with solicited local and systemic AEs (Pain, Erythema, Swelling, Induration, Fever -body temperature  38.0°C-, Nausea, Myalgia, Arthralgia, Headache, Fatigue) up to 7 days (including the day of vaccination) after Visits 1 and 2. | 7 days (including the day of vaccination) after Visits 1 and 2. | 
| Unsolicited AEs | The incidence of subjects with any other unsolicited AEs up to 7 days (including the day of vaccination) after Visits 1 and 2. | 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 | The incidence of subjects with 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) |