Research Trial Assessing the Immunogenicity and Safety of Three Meningococcal B Vaccine Strategies Among Patients With Asplenia.

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the immunological response and tolerance of 3 vaccine strategies against meningococcus B, a potentially fatal invasive infection.

Detailed Description
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Currently, in France, no immunogenicity data on Meningococcal B vaccines, neither with Bexsero® nor with Trumenba®, are available in asplenic patients, population at high risk of infection. As asplenic individuals (all causes) show less optimal immune response to conjugate meningococcal C vaccine compared to matched controls. [4], we hypothesize that a similar less optimal response may be expected for MenB vaccines among asplenic subjects. . That is why, we proposed in this study to evaluate two reinforced strategies with 3 administrations (M0, M1, and M6) of Bexsero® or Trumenba ®. Moreover, the study will also allow exploring the persistence of the immune response in this population. Indeed, few data are available on this persistence in the general population.

Official Title
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Multicenter, Randomized, Phase III, Trial Assessing the Immunogenicity and Safety of Three Meningococcal B Vaccine Strategies Among Patients With Asplenia

Conditions
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Splenectomy

Intervention / Treatment
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* Biological: Trumenba®
* Biological: Bexsero®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, >=18 to <=75 years old. Asplenic patient (for at least 2 weeks) with Howell Jolly bodies visible on blood film Splenectomy confirmed by consultation and/or hospitalization report or the ultrasound if it has been performed during the routine follow-up Women of childbearing age must have an effective contraception during the first 9 months of the study. Participants must give written consent prior to any trial procedure Participants must be covered by social security regimen or equivalent. Participants will be followed during the 4 years from the inclusion visit. Exclusion Criteria: History of meningococcal vaccination B. History of anaphylaxis post vaccination. Known allergy to any components (active substances or excipients) of both vaccines. Patients who cannot stop antibiotics 3 days before blood collection. Participants who have received any another vaccines within 4 weeks prior to immunization or who are planning to receive any vaccine within the first 7 months of the study (except the meningococcal ACWY vaccine, the anti-pneumococcal vaccine, the Haemophilus influenzae type B vaccine, the anti-Covid-19 vaccine), annual influenza vaccination which is permitted 2 weeks before and after each vaccination visit of the study and then allowed at any time during the study follow up). Parenteral Ig within the 3 months prior to VS or planned during the study. Chemotherapy agents within 6 months prior M0 or planning to take any during the study. Steroids (> 10mg/day; > 14 days) within the month preceding M0 or planning to take any during the study. Any pathology or condition that may impair the immune response, apart from splenectomy: immunosuppressive therapy in progress or in the 6 months prior to inclusion, hematopoietic stem cells allo / autograft, primary immunodeficiency, nephrotic syndrome, evolutive cancer, cirrhosis, known infection to HIV; Thrombocytopenia or any coagulation disorder contra-indicating intramuscularly injections. Pregnancy, breastfeeding or positive pregnancy test up to 7 months after inclusion. Severe acute febrile illness within the week before inclusion. Registration for any other clinical trial throughout the trial period except observational study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm A : Trumenba®: Standard vaccination<br>Two doses of 0.5 ml each at one month intervals, followed by a third dose given at 6 months after the second dose. | Biological: Trumenba®<br>* Trumenba® (Pfizer): Suspension for intramuscular injection in 0.5 mL single-dose prefilled.<br>|
| Other: Arm B:Bexsero®: standard vaccination regimen<br>Two doses of 0.5 ml each at one month intervals | Biological: Bexsero®<br>* Bexsero® (GSK): available as a suspension for intramuscular injection in a prefilled syringe<br>|
| Other: Arm C : Bexsero® Innovative vaccine strategy<br>Two doses of 0.5 ml each at one month intervals, followed by a third dose given at 6 months after the second dose. | Biological: Bexsero®<br>* Bexsero® (GSK): available as a suspension for intramuscular injection in a prefilled syringe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of responders defined as participants with seroconversion | Proportion of responders defined as participants with seroconversion (i.e. hSBA titer increases from <4 before vaccination to at least 4) or with hSBA titer showing a 4-fold increase (if hSBA titer was at least 4 before vaccination) one month after the completeness of three anti-meningococci B vaccine strategies (at M7 for all arms) in asplenic adults. | One month after the completeness of three anti-meningococci B vaccine strategies (at M7 for all arms) in asplenic adults. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Immunogenicity at M2/M7, i.e. one month after the completeness of each vaccine strategy: Serum bactericidal antibody (hSBA) Geometric Mean Titer (GMT). Proportion of responding participants using the conservative threshold of 8. Proportion of participants achieving an hSBA titer equal to or greater than the lower limit of quantification of the assay. | one month after the completeness of each vaccine strategy | 
| Persistence of immunogenicity | Persistence of immunogenicity at M12 M24, M36 and M48 for each vaccine strategy Serum bactericidal antibody (hSBA), GMT. Proportion of responding participants using the conservative threshold of 8. Proportion of participants achieving an SBA titre equal to or greater than the lower limit of quantification of the assay. | At M12 M24, M36 and M48 | 
| Modeling of the determinants of immunogenicity | Modeling of the determinants of immunogenicity: reason for splenectomy, age, gender, immunosuppressive or immunomodulatory agent | during the trial | 
| Any event or serious adverse event | Any event or serious adverse event during the trial possibly or not related to vaccine immunization. | 7 days following each vaccination. | 
| safety and effectiveness | To assess safety and effectiveness of Bexsero® and Trumenba® in asplenic adults older than 65 years of age. | through study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal B vaccine, vaccine strategies, splenectomized individuals