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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат Trumenba®
  Trumenba® (Pfizer): Suspension for intramuscular injection in 0.5 mL single-dose prefilled.
• Биопрепарат Bexsero®
  Bexsero® (GSK): available as a suspension for intramuscular injection in a prefilled syringe

Первичные конечные точки

• Proportion of responders defined as participants with seroconversion [Срок оценки: One month after the completeness of three anti-meningococci B vaccine strategies (at M7 for all arms) in asplenic adults.]

Вторичные конечные точки (5)

• Immunogenicity [Срок оценки: one month after the completeness of each vaccine strategy]
• Persistence of immunogenicity [Срок оценки: At M12 M24, M36 and M48]
• Modeling of the determinants of immunogenicity [Срок оценки: during the trial]
• Any event or serious adverse event [Срок оценки: 7 days following each vaccination.]
• safety and effectiveness [Срок оценки: through study completion]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Франция · 1 центр

• I-REIVAC/CIC1417 Cochin Hospital, AP-HP — Paris

Публикации

• 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. PMID 22947250
• 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. PMID 23954380
• 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 strai PMID 19534597
• 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. PMID 14688112
• 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.
• 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. PMID 24722351
• Wasserstrom H, Bussel J, Lim LC, Cunningham-Rundles C. Memory B cells and pneumococcal antibody after splenectomy. J Immunol. 2008 Sep 1;181(5):3684-9. doi: 10.4049/jimmunol.181.5.3684. PMID 18714044
• Mori M, Morris SC, Orekhova T, Marinaro M, Giannini E, Finkelman FD. IL-4 promotes the migration of circulating B cells to the spleen and increases splenic B cell survival. J Immunol. 2000 Jun 1;164(11):5704-12. doi: 10.4049/jimmunol.164.11.5704. PMID 10820247

Идентификаторы

NCT: NCT04166656 · P170938J · 2019-000924-17

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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