- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT07712926
Phase 3b Trial To Evaluate Safety And Immune Response (Superiority) of a Two-Dose Butantan-DV Regimen And The Standard Single Dose In Dengue-Naive Children/Adolescents and Immune Response (Non-inferiority) in a Manufacturing Facility Change (DEN-06-IB) (DEN-06-IB)
13. července 2026 aktualizováno: Butantan Institute
A Multicenter, Randomized, Controlled, Parallel-Group, Phase 3b Clinical Trial To Evaluate The Immunological Superiority Of The Two-Dose Butantan-Dv Regimen-Administered With A 9-Month Interval-Compared To The Single-Dose Regimen, And The Immunological Non-Inferiority Following A Change In Manufacturing Facility, In Children And Adolescents With No Prior Dengue Exposure.
This randomized, double-blind, three parallel-group, multicenter, phase 3b trial evaluates the safety and immunogenicity of Butantan-DV.
The study compares two primary immunization regimens (Butantan-DV/Butantan-DV vs. Butantan-DV/Placebo) across both the 2-11 and 12-17 age cohorts.
It also evaluates the manufacturing facility transition for the Butantan-DV dengue vaccine, by comparing the open-label arm WuXi Biologics (Butantan-DV group) to both double-blinded Butantan-DV/Butantan-DV and Butantan-DV/Placebo arms, in adolescents aged 12 to 17.
Přehled studie
Postavení
Zatím nenabíráme
Podmínky
Intervence / Léčba
Detailní popis
This randomized three parallel-group trial (one open-label, two double-blinded) evaluates the safety and humoral immunogenicity of a 0.5 mL dose (subcutaneously) of the tetravalent Butantan-DV vaccine against four dengue virus serotypes (DENV-1-4).
It will address the two-dose primary immunization regimen superiority in children (2-11 years) or adolescents (12-17 years), in comparison to the one dose regimen versus placebo on Day 29 post second vaccination.
The manufacturing facility transition for the Butantan-DV dengue vaccine will evaluate the non-inferiority of humoral immunogenicity between WuXi Biologics formulation (Butantan-DV WuXi) against both Butantan-DV (IB) arms, on Day 29 post first vaccination, in adolescents (12-17 years).
Safety endpoint consists in local or systemic solicited and unsolicited adverse events, in children and adolescents up to Day 22 after each vaccine dose.
Typ studie
Intervenční
Zápis (Odhadovaný)
1765
Fáze
- Fáze 3
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní kontakt
- Jméno: Fernanda C Boulos, MD, PhD
- Telefonní číslo: +551137237054
- E-mail: fernanda.boulos@fundacaobutantan.org.br
Studijní záloha kontaktů
- Jméno: Érique JF Peixoto de Miranda, MD, PhD
- Telefonní číslo: +551137237054
- E-mail: erique.miranda@fundacaobutantan.org.br
Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dítě
Přijímá zdravé dobrovolníky
Ano
Popis
Inclusion Criteria:
- Participants aged 2 to 17 years at the time of study enrollment with no prior dengue exposure (as determined by IgG ELISA), at research centers located in cities within areas of low to medium endemicity for dengue virus infection.
- Agreement to periodic contact via telephone, electronic means, and home or research center visits.
- Participants of reproductive potential must be using an effective contraceptive method for at least 30 days at screening and continue doing so until Day 363 post-first vaccination; exceptions apply if the participant (or their legal representative) declares the participant to be at no risk of pregnancy-whether due to sexual abstinence or engaging in non-reproductive sexual practices-through Day 363 post-first vaccination.
- Demonstrated intention to participate in the study, documented by the signature of the informed consent form by the participant's parents and the informed assent form by the participant (where applicable), as well as agreement to study procedures, including completing participant diaries, undergoing blood sampling, and being available for scheduled study visits and contacts.
Exclusion Criteria:
- Reactive or unavailable dengue IgG ELISA test result.
- For female participants of reproductive potential: pregnancy (confirmed by a positive β-hCG test), breastfeeding, or expressed intention to engage in sexual practices with reproductive potential without using a contraceptive method up to Day 363 after the first vaccination;
- Planned donation of blood, semen, or ova up to Day 363 after the first vaccination;
- Evidence of active, uncontrolled neurological, cardiac, pulmonary, hepatic, or renal disease-defined as disease requiring a change in treatment or hospitalization due to worsening of the condition within the 90 days prior to study screening, based on medical history or physical examination, at the investigator's judgement;
- Diseases compromising the immune system, including: decompensated diabetes mellitus; active neoplasms or a history of neoplasms within the last five years (except basal cell carcinoma); congenital or acquired immunodeficiencies (except HIV infection with undetectable viral load and CD4+ T-lymphocyte count > 500 cells/mm³); solid organ transplantation (heart, liver, pancreas, lung, kidney); or uncontrolled autoimmune diseases (based on medical history or physical examination); as well as a history of hepatic insufficiency, heart failure, or end-stage or dialysis-dependent chronic kidney disease;
- Behavioral, cognitive, or psychiatric condition that, in the opinion of the principal investigator or their medical representative, affects the potential participant's ability to understand and comply with the study protocol requirements;
- Any use of alcohol or drugs considered abusive within the 12 months prior to study enrollment that has caused medical, occupational, or family problems, as indicated by clinical history;
- History of severe allergic reaction or anaphylaxis to the study vaccine or its components;
- History of asplenia;
- Participation in another clinical trial involving the administration of an investigational product during the six months prior to study enrollment, or participation in another clinical trial during the 12 months following enrollment;
- Prior participation in a clinical study of (or exposure to) any dengue vaccine;
- Use of potent immunosuppressive therapies (excluding corticosteroids) in the six months prior to study enrollment. Potent immunosuppressive therapies are considered to include: antineoplastic chemotherapy, radiotherapy, immunosuppressants used to induce transplant tolerance, and potent monoclonal antibody therapy for the treatment of rheumatological diseases, among others;
- Receipt of an immunosuppressive dose of corticosteroids within the three months prior to study enrollment. An immunosuppressive corticosteroid dose is defined as equivalent to a prednisone dose of 2 mg/kg/day for children and 20 mg/day for adolescents for 14 days (a cumulative equivalent dose of at least 280 mg of prednisone). Continuous use of topical or nasal corticosteroids is not considered immunosuppressive;
- Receipt of blood components (transfusions) or blood derivatives (immunoglobulins) within the six months prior to study enrollment;
- Any other condition that, in the opinion of the principal investigator or their medical representative, could jeopardize the safety or rights of a potential participant or prevent them from complying with this protocol.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Prevence
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: Butantan-DV (IB) - Intervention 1
Butantan-DV manufactured at the Butantan Institute
|
Butantan-DV manufactured at the Instituto Butantan - Butantan-DV (IB), mean 10³ PFU (per dose), subcutaneously, in the deltoid region.
|
|
Experimentální: Butantan-DV (WuXi) - Intervention 2
Butantan-DV manufactured at the WuXi Biologics CRDMO
|
Butantan-DV manufactured at the WuXi Biologics CRDMO - Butantan-DV (WuXi),mean 10³ PFU (per dose), subcutaneously, in the deltoid region.
|
|
Komparátor placeba: Placebo (IB)
Placebo (0 PFU), solution of the simplified lyophilized formulation, manufactured at the Butantan Institute
|
Placebo manufactured at the Instituto Butantan - Placebo (IB), mean 0 PFU (per dose), subcutaneously, in the deltoid region.
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Immunogenicity - 1
Časové okno: Group Butantan-DV (IB) + Butantan-DV (IB) on Day 302 and Group Butantan-DV (IB) + Placebo (IB) on Day 29 post vaccination.
|
Geometric Mean Fold-Rise ratio of neutralizing antibodies measured by PRNT50 against the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) in participants in the Butantan-DV (IB) + Butantan-DV (IB) group, compared to participants in the Butantan-DV (IB) + Placebo (IB) group, in children aged 2 to 11 years.
|
Group Butantan-DV (IB) + Butantan-DV (IB) on Day 302 and Group Butantan-DV (IB) + Placebo (IB) on Day 29 post vaccination.
|
|
Immunogenicity - 2
Časové okno: Group Butantan-DV (IB) + Butantan-DV (IB) on Day 302 and Group Butantan-DV (IB) + Placebo (IB) on Day 29 post vaccination.
|
Geometric Mean Fold-Rise ratio of neutralizing antibodies measured by PRNT50 against the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) in participants of the Butantan-DV (IB) + Butantan-DV (IB) group at Day 302, compared to participants of the Butantan-DV (IB) + Placebo (IB) group at Day 29, in adolescents aged 12 to 17 years.
|
Group Butantan-DV (IB) + Butantan-DV (IB) on Day 302 and Group Butantan-DV (IB) + Placebo (IB) on Day 29 post vaccination.
|
|
Immunogenicity - 3
Časové okno: Day 29 post vaccination.
|
Geometric Mean Fold-Rise ratio of neutralizing antibodies measured by PRNT50 against the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) in participants of the Butantan-DV (WuXi) Group compared to participants of the other two Butantan-DV (IB) groups, in adolescents aged 12 to 17 years.
|
Day 29 post vaccination.
|
|
Safety - 1
Časové okno: First 21 days after each vaccine dose (up to Day 22 and from Day 273 to Day 294).
|
Frequency of solicited and unsolicited adverse reactions in participants in the Butantan-DV + Butantan-DV group and in participants in the Butantan-DV (IB) + Placebo (IB) group, among children aged 2 to 11 years.
|
First 21 days after each vaccine dose (up to Day 22 and from Day 273 to Day 294).
|
|
Safety - 2
Časové okno: First 21 days after each vaccine dose (up to Day 22 and from Day 273 to Day 294).
|
Frequency of solicited and unsolicited adverse reactions after each vaccine dose in participants in the Butantan-DV (IB) + Butantan-DV (IB) group and in participants in the Butantan-DV (IB) + Placebo (IB) group, among adolescents aged 12 to 17 years.
|
First 21 days after each vaccine dose (up to Day 22 and from Day 273 to Day 294).
|
|
Safety - 3
Časové okno: First 21 days after each vaccine dose (up to Day 22).
|
Frequency of solicited and unsolicited adverse reactions in participants in the Butantan-DV (WuXi) Group and in participants in the other two Butantan-DV (IB) groups who received the first dose of the primary immunization series, among adolescents aged 12 to 17 years.
|
First 21 days after each vaccine dose (up to Day 22).
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Immunogenicity - 4
Časové okno: Day 29 postvaccination.
|
Geometric Mean Fold-Rise ratio (rGMFR) in neutralizing antibody titers measured by PRNT50, for each dengue virus serotype (DENV-1, DENV-2, DENV-3, and DENV-4), postvaccination, for participants in the Butantan-DV (IB) + Butantan-DV (IB) group compared to participants in the Butantan-DV (IB) + Placebo (IB) group, among children aged 2 to 11 years and adolescents aged 12 to 17 years.
|
Day 29 postvaccination.
|
|
Immunogenicity - 5
Časové okno: Day 182 postvaccination.
|
Geometric Mean Fold-Rise ratio (rGMFR) of neutralizing antibody titers measured by PRNT50-for each dengue virus serotype (DENV-1, DENV-2, DENV-3, and DENV-4)-comparing the Butantan-DV (WuXi) Group to the other Butantan-DV (IB) groups that received only the first vaccination.
|
Day 182 postvaccination.
|
|
Immunogenicity - 6
Časové okno: Day 302 in the Butantan-DV (IB) + Butantan-DV (IB) Group and Day 29 in the Butantan-DV (IB) + Placebo (IB) Group.
|
Difference between proportions of seroconversion (95% CI) in the Butantan-DV (IB) + Butantan-DV (IB) group and seroconversion in the Butantan-DV (IB) + Placebo (IB) group, for the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4).
Seroconversion defined as ≥1:10 from a baseline titer <1:10 post-vaccination or a fourfold increase relative to baseline for a baseline titer ≥1:10.
|
Day 302 in the Butantan-DV (IB) + Butantan-DV (IB) Group and Day 29 in the Butantan-DV (IB) + Placebo (IB) Group.
|
|
Immunogenicity - 7
Časové okno: Days 1, 29, 182, 302, and 456 post vaccination.
|
Cellular immune response in a cohort of 50 consecutive participants from the Butantan-DV (IB) + Butantan-DV (IB) group and the Butantan-DV (IB) + Placebo (IB) group, against the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4).
The immune response will consist of the proportion (%) of DENV-1- through DENV-4-specific CD4+ and CD8+ T cells (producing IFN-γ) following vaccine stimulation.
|
Days 1, 29, 182, 302, and 456 post vaccination.
|
|
Safety - 4
Časové okno: Period between the second dose and Day 294.
|
Frequency (95% CI and p-value) for the difference in proportions of participants with solicited (local and systemic) and unsolicited adverse reactions comparing the Butantan-DV (IB) + Butantan-DV (IB) group with the Butantan-DV (IB) + Placebo (IB) group, in children aged 2 to 11 years and adolescents aged 12 to 17 years.
|
Period between the second dose and Day 294.
|
|
Safety - 5
Časové okno: Period between the first dose and Day 22.
|
Frequency (95% CI and p-value) for the difference in proportions of participants with solicited (local and systemic) and unsolicited adverse reactions, among participants in the Butantan-DV (WuXi) Group and participants in the other Butantan-DV (IB) groups who received the first dose of the primary immunization series, in adolescents aged 12 to 17 years.
|
Period between the first dose and Day 22.
|
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Safety - 6
Časové okno: Day 1 to Day 43 and Day 273 to Day 315
|
Frequency (95% CI) of the difference in proportions of participants with adverse events requiring medical attention (AERMA) post-vaccination across the three groups, in children aged 2 to 11 years and adolescents aged 12 to 17 years.
|
Day 1 to Day 43 and Day 273 to Day 315
|
|
Safety - 7
Časové okno: Throughout the entire study period, an average of 1 year.
|
Frequency (95% CI and p-value) of the difference between proportions, of participants with serious adverse events (SAEs) post-vaccination across the three groups, among children aged 2 to 11 and adolescents aged 12 to 17 years.
|
Throughout the entire study period, an average of 1 year.
|
|
Safety - 8
Časové okno: Throughout the entire study period, an average of 1 year.
|
Frequency (95% CI and p-value) of the difference in proportions of participants with adverse events of special interest (AESI) post-vaccination, across the three groups, in children aged 2 to 11 years and adolescents aged 12 to 17 years.
|
Throughout the entire study period, an average of 1 year.
|
|
Safety - 9
Časové okno: Throughout the entire study period, an average of 1 year.
|
Frequency (95% CI and p-value) of the difference in proportions of participants with adverse events of special interest (AESI) post-vaccination, across the three groups, in children aged 2 to 11 years and adolescents aged 12 to 17 years.
|
Throughout the entire study period, an average of 1 year.
|
|
Safety - 10
Časové okno: Days 1, 6, 9, 12, 22, 273, 279, 282, 285, and 294.
|
Frequency of viremia after each dose of the primary immunization and laboratory changes at visits on in a cohort of 50 adolescent participants aged 12 to 17 years from the Butantan-DV (IB) + Butantan-DV (IB) group and the Butantan-DV (IB) + Placebo (IB) group, for all dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) and by valence.
|
Days 1, 6, 9, 12, 22, 273, 279, 282, 285, and 294.
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Spolupracovníci
Vyšetřovatelé
- Ředitel studie: Fernanda C Boulos, MD, PhD, Instituto Butantan
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Obecné publikace
- 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.
- 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.
- 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.
- Peixoto de Miranda EJF, de Sousa Moreira JA, da Silva Braga R, Silveira DHR, Infante V, de Oliveira Alves LB, de Camargo Vieira Tenorio J, Dos Santos Silva GF, Patino EG, de Mesquita Pacheco PHT, Ramos F, Oliveira DS, Kallas EG, Boulos FC. Randomized, double-blind, placebo-controlled, phase 3 trial to demonstrate lot-to-lot consistency of 3 lots of the simplified formulation of Butantan-dengue vaccine. Vaccine. 2025 Nov 14;66:127836. doi: 10.1016/j.vaccine.2025.127836. Epub 2025 Oct 14.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Odhadovaný)
1. února 2027
Primární dokončení (Odhadovaný)
28. února 2028
Dokončení studie (Odhadovaný)
20. prosince 2028
Termíny zápisu do studia
První předloženo
8. července 2026
První předloženo, které splnilo kritéria kontroly kvality
13. července 2026
První zveřejněno (Aktuální)
20. července 2026
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
20. července 2026
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
13. července 2026
Naposledy ověřeno
1. července 2026
Více informací
Termíny související s touto studií
Klíčová slova
Další identifikační čísla studie
- DEN-06-IB
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Ne
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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