Open forum infectious diseases · 2024
4CMenB Breadth of Immune Response, Immunogenicity, and Safety: Results From a Phase 3 Randomized, Controlled, Observer Blind Study in Adolescents and Young Adults.
Клиническое исследованиеСтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Nolan Terry, Bhusal Chiranjiwi, Beran Jiří, Bloch Mark, Cetin Benhur S, Dinleyici Ener C, Dražan Daniel, Kokko Satu, Koski Susanna, Laajalahti Outi, Langley Joanne M, Rämet Mika, Richmond Peter C, Silas Peter, Tapiero Bruce, Tiong Florence, Tipton Mary, Ukkonen Benita, Ulukol Betul, Lattanzi Maria, Trapani Mauro, Willemsen Arnold, Toneatto Daniela, QUINTET study group
Аннотация
BACKGROUND: Meningococcal serogroup B (MenB) strains are highly diverse. Breadth of immune response for the MenB vaccine, 4CMenB, administered at 0-2, 0-6, or 0-2-6 months, was demonstrated by endogenous complement-human serum bactericidal antibody (enc-hSBA) assay against an epidemiologically relevant panel of 110 MenB strains.
METHODS: In a phase 3 trial, 3651 healthy 10- to 25-year-old participants were randomized 5:5:9:1 to receive 4CMenB (0-6 schedule), 4CMenB (0-2-6 schedule), investigational MenABCWY vaccine, or control MenACWY-CRM vaccine. The primary objectives were to evaluate safety and demonstrate breadth of immune response by enc-hSBA assay against the MenB strain panel using test-based (percentage of samples without bactericidal activity against strains after 4CMenB vs control vaccination) and responder-based (percentage of participants whose postvaccination sera kill ≥70% strains) approaches. Success was demonstrated with 2-sided 97.5% confidence interval (CI) lower limit >65%. Immunogenicity was assessed by traditional hSBA assay against four indicator strains.
RESULTS: Breadth of immune response (test-based) was 78.7% (97.5% CI, 77.2-80.1), 81.8% (80.4-83.1), 83.2% (81.9-84.4) for the 0-2, 0-6, and 0-2-6 schedules, respectively, and (responder-based) 84.8% (81.8-87.5), 89.8% (87.2-92.0), and 93.4% (91.2-95.2), respectively. No clinically relevant differences in immunogenicity were observed across schedules. 4CMenB was well tolerated.
CONCLUSIONS: The 2-dose (0-2, 0-6) 4CMenB schedules met predefined criteria for success for both breadth of immune response endpoints against a diverse MenB strain panel, had comparable immunogenicity, and safety in line with the established 4CMenB safety profile. The 3-dose schedule provided no additional immunological benefit, supporting use of the 4CMenB 0-2 schedule.
METHODS: In a phase 3 trial, 3651 healthy 10- to 25-year-old participants were randomized 5:5:9:1 to receive 4CMenB (0-6 schedule), 4CMenB (0-2-6 schedule), investigational MenABCWY vaccine, or control MenACWY-CRM vaccine. The primary objectives were to evaluate safety and demonstrate breadth of immune response by enc-hSBA assay against the MenB strain panel using test-based (percentage of samples without bactericidal activity against strains after 4CMenB vs control vaccination) and responder-based (percentage of participants whose postvaccination sera kill ≥70% strains) approaches. Success was demonstrated with 2-sided 97.5% confidence interval (CI) lower limit >65%. Immunogenicity was assessed by traditional hSBA assay against four indicator strains.
RESULTS: Breadth of immune response (test-based) was 78.7% (97.5% CI, 77.2-80.1), 81.8% (80.4-83.1), 83.2% (81.9-84.4) for the 0-2, 0-6, and 0-2-6 schedules, respectively, and (responder-based) 84.8% (81.8-87.5), 89.8% (87.2-92.0), and 93.4% (91.2-95.2), respectively. No clinically relevant differences in immunogenicity were observed across schedules. 4CMenB was well tolerated.
CONCLUSIONS: The 2-dose (0-2, 0-6) 4CMenB schedules met predefined criteria for success for both breadth of immune response endpoints against a diverse MenB strain panel, had comparable immunogenicity, and safety in line with the established 4CMenB safety profile. The 3-dose schedule provided no additional immunological benefit, supporting use of the 4CMenB 0-2 schedule.