Clinical trial NCT04166656: Research Trial Assessing the Immunogenicity and Safety of Three Meningococcal B Vaccine Strategies Among Patients With Asplenia.
Official title: Multicenter, Randomized, Phase III, Trial Assessing the Immunogenicity and Safety of Three Meningococcal B Vaccine Strategies Among Patients With Asplenia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Splenectomy
Keywords: Meningococcal B vaccine
vaccine strategies
splenectomized individuals
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: EUCLID Clinical Trial Platform
name: Recherche Clinique Paris Descartes Necker Cochin Sainte Anne
name: CIC 1417 Cochin-Pasteur
name: Innovative clinical research in vaccinologie (I-REIVAC)
name: Institut Pasteur
First posted: 2019-11-18
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female, \>=18 to \<=75 years old.
2. Asplenic patient (for at least 2 weeks) with Howell Jolly bodies visible on blood film
3. Splenectomy confirmed by consultation and/or hospitalization report or the ultrasound if it has been performed during the routine follow-up
4. Women of childbearing age must have an effective contraception during the first 9 months of the study.
5. Participants must give written consent prior to any trial procedure
6. Participants must be covered by social security regimen or equivalent.
7. Participants will be followed during the 4 years from the inclusion visit.

Exclusion Criteria:

1. History of meningococcal vaccination B.
2. History of anaphylaxis post vaccination.
3. Known allergy to any components (active substances or excipients) of both vaccines.
4. Patients who cannot stop antibiotics 3 days before blood collection.
5. 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).
6. Parenteral Ig within the 3 months prior to VS or planned during the study.
7. Chemotherapy agents within 6 months prior M0 or planning to take any during the study.
8. Steroids (\> 10mg/day; \> 14 days) within the month preceding M0 or planning to take any during the study.
9. 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;
10. Thrombocytopenia or any coagulation disorder contra-indicating intramuscularly injections.
11. Pregnancy, breastfeeding or positive pregnancy test up to 7 months after inclusion.
12. Severe acute febrile illness within the week before inclusion.
13. Registration for any other clinical trial throughout the trial period except observational study.

Primary outcomes:
measure: Proportion of responders defined as participants with seroconversion
timeFrame: One month after the completeness of three anti-meningococci B vaccine strategies (at M7 for all arms) in asplenic adults.
Secondary outcomes:
measure: Immunogenicity
timeFrame: one month after the completeness of each vaccine strategy
measure: Persistence of immunogenicity
timeFrame: At M12 M24, M36 and M48
measure: Modeling of the determinants of immunogenicity
timeFrame: during the trial
measure: Any event or serious adverse event
timeFrame: 7 days following each vaccination.
measure: safety and effectiveness
timeFrame: through study completion
Other outcomes:
Locations:
city: Paris
country: France
facility: I-REIVAC/CIC1417 Cochin Hospital, AP-HP
Study officials:
affiliation: CIC 1417 Clinical Center Investigation
name: Odile LAUNAY, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Pasteur
name: MUHAMED-KHEIR TAHA, MD, PHD
role: STUDY_DIRECTOR
References:
citation: Borrow R. Advances with vaccination against Neisseria meningitidis. Trop Med Int Health. 2012 Dec;17(12):1478-91. doi: 10.1111/j.1365-3156.2012.03085.x. Epub 2012 Sep 4.
citation: Frosi G, Biolchi A, Lo Sapio M, Rigat F, Gilchrist S, Lucidarme J, Findlow J, Borrow R, Pizza M, Giuliani MM, Medini D. Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage. Vaccine. 2013 Oct 9;31(43):4968-74. doi: 10.1016/j.vaccine.2013.08.006. Epub 2013 Aug 14.
citation: Murphy E, Andrew L, Lee KL, Dilts DA, Nunez L, Fink PS, Ambrose K, Borrow R, Findlow J, Taha MK, Deghmane AE, Kriz P, Musilek M, Kalmusova J, Caugant DA, Alvestad T, Mayer LW, Sacchi CT, Wang X, Martin D, von Gottberg A, du Plessis M, Klugman KP, Anderson AS, Jansen KU, Zlotnick GW, Hoiseth SK. Sequence diversity of the factor H binding protein vaccine candidate in epidemiologically relevant strains of serogroup B Neisseria meningitidis. J Infect Dis. 2009 Aug 1;200(3):379-89. doi: 10.1086/600141.
citation: Balmer P, Falconer M, McDonald P, Andrews N, Fuller E, Riley C, Kaczmarski E, Borrow R. Immune response to meningococcal serogroup C conjugate vaccine in asplenic individuals. Infect Immun. 2004 Jan;72(1):332-7. doi: 10.1128/IAI.72.1.332-337.2004.
citation: 5. Hcsp. Avis du hcsp relatif à l'utilisation du vaccin bexsero® (novartis vaccines and diagnostics). 2013. (link:http://www.hcsp.fr/explore.cgi/telecharger?nomfichier=hcspa20131025_vaccmeningocoquebbexsero®.pdf.
citation: McQuaid F, Snape MD, John TM, Kelly S, Robinson H, Houlden J, Voysey M, Toneatto D, Kitte C, Dull PM, Pollard AJ. Persistence of bactericidal antibodies to 5 years of age after immunization with serogroup B meningococcal vaccines at 6, 8, 12 and 40 months of age. Pediatr Infect Dis J. 2014 Jul;33(7):760-6. doi: 10.1097/INF.0000000000000327.
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citation: Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969 Jun 1;129(6):1307-26. doi: 10.1084/jem.129.6.1307.