Butantan-DV Vaccine in Elderly Populations (DEN-04-IB)

Summary

This is a randomized, double-blind (60 -79 years) and open-label (40-59 years), three-arm parallel Phase 3b, multicenter study to evaluate the safety and non-inferiority of the humoral immune response of the Butantan Dengue vaccine (Dengue 1,2,3,4 (attenuated)) in participants aged 60 -79 years (elderly) compared to participants aged 40 to 59 years (adults), with or without previous dengue and healthy based on clinical examination.

Timeline

Start

2026-03-03

Primary completion

2027-03

Completion

2027-10

Publications

• Background Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev. 1998 Jul;11(3):480-96. doi: 10.1128/CMR.11.3.480.
• Background Laydon DJ, Dorigatti I, Hinsley WR, Nedjati-Gilani G, Coudeville L, Ferguson NM. Efficacy profile of the CYD-TDV dengue vaccine revealed by Bayesian survival analysis of individual-level phase III data. Elife. 2021 Jul 2;10:e65131. doi: 10.7554/eLife.65131.
• Background Patel SS, Rauscher M, Kudela M, Pang H. Clinical Safety Experience of TAK-003 for Dengue Fever: A New Tetravalent Live Attenuated Vaccine Candidate. Clin Infect Dis. 2023 Feb 8;76(3):e1350-e1359. doi: 10.1093/cid/ciac418.
• Background Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS. Development of a live attenuated dengue virus vaccine using reverse genetics. Viral Immunol. 2006 Spring;19(1):10-32. doi: 10.1089/vim.2006.19.10.
• Background Kallas EG, Precioso AR, Palacios R, Thome B, Braga PE, Vanni T, Campos LMA, Ferrari L, Mondini G, da Graca Salomao M, da Silva A, Espinola HM, do Prado Santos J, Santos CLS, Timenetsky MDCST, Miraglia JL, Gallina NMF, Weiskopf D, Sette A, Goulart R, Salles RT, Maestri A, Sallum AME, Farhat SCL, Sakita NK, Ferreira JCOA, Silveira CGT, Costa PR, Raw I, Whitehead SS, Durbin AP, Kalil J. Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial. Lancet Infect Dis. 2020 Jul;20(7):839-850. doi: 10.1016/S1473-3099(20)30023-2. Epub 2020 Mar 24.
• Background Kallas EG, Cintra MAT, Moreira JA, Patino EG, Braga PE, Tenorio JCV, Infante V, Palacios R, de Lacerda MVG, Batista Pereira D, da Fonseca AJ, Gurgel RQ, Coelho IC, Fontes CJF, Marques ETA, Romero GAS, Teixeira MM, Siqueira AM, Barral AMP, Boaventura VS, Ramos F, Elias Junior E, Cassio de Moraes J, Covas DT, Kalil J, Precioso AR, Whitehead SS, Esteves-Jaramillo A, Shekar T, Lee JJ, Macey J, Kelner SG, Coller BG, Boulos FC, Nogueira ML. Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults. N Engl J Med. 2024 Feb 1;390(5):397-408. doi: 10.1056/NEJMoa2301790.
• Background Chiaravalloti-Neto F, da Silva RA, Zini N, da Silva GCD, da Silva NS, Parra MCP, Dibo MR, Estofolete CF, Favaro EA, Dutra KR, Mota MTO, Guimaraes GF, Terzian ACB, Blangiardo M, Nogueira ML. Seroprevalence for dengue virus in a hyperendemic area and associated socioeconomic and demographic factors using a cross-sectional design and a geostatistical approach, state of Sao Paulo, Brazil. BMC Infect Dis. 2019 May 20;19(1):441. doi: 10.1186/s12879-019-4074-4.
• Background Schneider M, Narciso-Abraham M, Hadl S, McMahon R, Toepfer S, Fuchs U, Hochreiter R, Bitzer A, Kosulin K, Larcher-Senn J, Mader R, Dubischar K, Zoihsl O, Jaramillo JC, Eder-Lingelbach S, Buerger V, Wressnigg N. Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 24;401(10394):2138-2147. doi: 10.1016/S0140-6736(23)00641-4. Epub 2023 Jun 12.
• Background Casey RM, Harris JB, Ahuka-Mundeke S, Dixon MG, Kizito GM, Nsele PM, Umutesi G, Laven J, Kosoy O, Paluku G, Gueye AS, Hyde TB, Ewetola R, Sheria GKM, Muyembe-Tamfum JJ, Staples JE. Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Final Report. N Engl J Med. 2019 Aug 1;381(5):444-454. doi: 10.1056/NEJMoa1710430. Epub 2018 Feb 14.
• Background Hou Y, Chen M, Bian Y, Hu Y, Chuan J, Zhong L, Zhu Y, Tong R. Insights into vaccines for elderly individuals: from the impacts of immunosenescence to delivery strategies. NPJ Vaccines. 2024 Apr 10;9(1):77. doi: 10.1038/s41541-024-00874-4.
• Background Weinberg A, Lazar AA, Zerbe GO, Hayward AR, Chan IS, Vessey R, Silber JL, MacGregor RR, Chan K, Gershon AA, Levin MJ. Influence of age and nature of primary infection on varicella-zoster virus-specific cell-mediated immune responses. J Infect Dis. 2010 Apr 1;201(7):1024-30. doi: 10.1086/651199.
• Background Levin MJ, Oxman MN, Zhang JH, Johnson GR, Stanley H, Hayward AR, Caulfield MJ, Irwin MR, Smith JG, Clair J, Chan IS, Williams H, Harbecke R, Marchese R, Straus SE, Gershon A, Weinberg A; Veterans Affairs Cooperative Studies Program Shingles Prevention Study Investigators. Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine. J Infect Dis. 2008 Mar 15;197(6):825-35. doi: 10.1086/528696.
• Background Collier DA, Ferreira IATM, Kotagiri P, Datir RP, Lim EY, Touizer E, Meng B, Abdullahi A; CITIID-NIHR BioResource COVID-19 Collaboration; Elmer A, Kingston N, Graves B, Le Gresley E, Caputo D, Bergamaschi L, Smith KGC, Bradley JR, Ceron-Gutierrez L, Cortes-Acevedo P, Barcenas-Morales G, Linterman MA, McCoy LE, Davis C, Thomson E, Lyons PA, McKinney E, Doffinger R, Wills M, Gupta RK. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature. 2021 Aug;596(7872):417-422. doi: 10.1038/s41586-021-03739-1. Epub 2021 Jun 30.
• Background Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA. 1983 Apr 1;249(13):1743-5. No abstract available.
• Background Musso D, Ko AI, Baud D. Zika Virus Infection - After the Pandemic. N Engl J Med. 2019 Oct 10;381(15):1444-1457. doi: 10.1056/NEJMra1808246. No abstract available.
• Background Wang WW, Mehrotra DV, Chan IS, Heyse JF. Statistical considerations for noninferiority/equivalence trials in vaccine development. J Biopharm Stat. 2006;16(4):429-41. doi: 10.1080/10543400600719251.
• Background Donken R, de Melker HE, Rots NY, Berbers G, Knol MJ. Comparing vaccines: a systematic review of the use of the non-inferiority margin in vaccine trials. Vaccine. 2015 Mar 17;33(12):1426-32. doi: 10.1016/j.vaccine.2015.01.072. Epub 2015 Feb 7.
• Background Tricou V, Winkle PJ, Tharenos LM, Rauscher M, Escudero I, Hoffman E, LeFevre I, Borkowski A, Wallace D. Consistency of immunogenicity in three consecutive lots of a tetravalent dengue vaccine candidate (TAK-003): A randomized placebo-controlled trial in US adults. Vaccine. 2023 Nov 13;41(47):6999-7006. doi: 10.1016/j.vaccine.2023.09.049. Epub 2023 Oct 24.
• Background Torresi J, Heron LG, Qiao M, Marjason J, Chambonneau L, Bouckenooghe A, Boaz M, van der Vliet D, Wallace D, Hutagalung Y, Nissen MD, Richmond PC. Lot-to-lot consistency of a tetravalent dengue vaccine in healthy adults in Australia: a randomised study. Vaccine. 2015 Sep 22;33(39):5127-34. doi: 10.1016/j.vaccine.2015.08.008. Epub 2015 Aug 13.
• Background LeFevre I, Bravo L, Folschweiller N, Medina EL, Moreira ED Jr, Nordio F, Sharma M, Tharenos LM, Tricou V, Watanaveeradej V, Winkle PJ, Biswal S. Bridging the immunogenicity of a tetravalent dengue vaccine (TAK-003) from children and adolescents to adults. NPJ Vaccines. 2023 May 25;8(1):75. doi: 10.1038/s41541-023-00670-6.
• Background Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985 Apr-Jun;4(2):213-26. doi: 10.1002/sim.4780040211.
• Results Nogueira ML, Cintra MAT, Moreira JA, Patino EG, Braga PE, Tenorio JCV, de Oliveira Alves LB, Infante V, Silveira DHR, de Lacerda MVG, Pereira DB, da Fonseca AJ, Gurgel RQ, Coelho IC, Fontes CJF, Marques ETA, Romero GAS, Teixeira MM, Siqueira AM, Boaventura VS, Ramos F, Junior EE, de Moraes JC, Whitehead SS, Esteves-Jaramillo A, Shekar T, Lee JJ, Macey J, Kelner SG, Coller BG, Boulos FC, Kallas EG; Phase 3 Butantan-DV Working Group. Efficacy and safety of Butantan-DV in participants aged 2-59 years through an extended follow-up: results from a double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil. Lancet Infect Dis. 2024 Nov;24(11):1234-1244. doi: 10.1016/S1473-3099(24)00376-1. Epub 2024 Aug 5.

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