DenguePhase 3DEN-04-IBNCT06891950
Butantan-DV Vaccine in Elderly Populations (DEN-04-IB)
A Phase 3 study testing Dengue 1,2,3,4 (attenuated) vaccine in people with Dengue, run by Butantan Institute at 5 sites in Brazil.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Dengue
- What is being tested?
- Dengue 1,2,3,4 (attenuated) vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 997 participants
- Where
- 5 sitesBrazil
- Study dates
- 3 Mar 2026to Oct 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- a. Healthy participants aged between 40 and 79 years at the time of study entry, with or without a history of exposure to dengue fever;
- Agree to periodic contact by telephone, electronic means, and home visits and to the research center;
- Participants with reproductive potential must be using some effective contraceptive method at screening and continue using it for up to 90 days after the intervention; except in cases where the volunteer declares that she is not at risk of becoming pregnant, either by not engaging in sexual activities or by engaging in them in a non-reproductive manner, up to 90 days after vaccination;
- Demonstrate intent to participate in the study, documented by the participant's signature of the informed consent form, as well as the study procedures, including completing the Participant Diaries, blood collection, and being available for scheduled study visits and contacts.
Who cannot join
- a. For female participants with reproductive potential: pregnancy (confirmed by positive β-hCG test), breastfeeding or manifest intention to have sexual practices with reproductive potential without using a contraceptive method in the 90 days following vaccination;
- Planned donation of blood, semen or eggs in the 90 days following vaccination;
- Evidence of active uncontrolled neurological, cardiac, pulmonary, hepatic or renal disease according to anamnesis or physical examination, at the discretion of the investigator;
- Diseases that compromise the immune system, including: decompensated diabetes mellitus, active neoplasms or history of neoplasms in the last five years (except basal cell carcinoma), congenital or acquired immunodeficiencies (including HIV/AIDS), solid organ transplants (heart, liver, pancreas, lung, kidney) or uncontrolled autoimmune diseases according to anamnesis or physical examination, as well as a history of liver failure, heart failure or terminal chronic kidney disease or dialysis;
- Behavioral, cognitive, or psychiatric illness that, in the opinion of the principal investigator or his/her medical representative, affects the potential participant's ability to understand and comply with the requirements of the study protocol;
- Any abuse of alcohol or drugs in the last 12 months prior to enrollment in the study that has caused medical, professional, or family problems, as indicated by the clinical history;
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- History of severe allergic reaction or anaphylaxis to the vaccine or components of the study vaccine;
- History of asplenia;
- Participation in another clinical trial with administration of an investigational product during the six months prior to enrollment in the study or scheduled participation in another clinical trial in the 12 months following enrollment;
- Previous participation in a dengue vaccine evaluation study or previous exposure to dengue vaccine;
- Use of immunosuppressive therapies six months prior to enrollment in the study or their scheduled use in the 12 months following enrollment. The following immunosuppressive therapies will be considered: antineoplastic chemotherapy, radiotherapy, immunosuppressants to induce tolerance to transplants, monoclonal antibody therapy for the treatment of rheumatological diseases, among others;
- l.Having received an immunosuppressive dose of corticosteroid in the last three months prior to inclusion in the study or administration of an immunosuppressive dose of corticosteroid for the 12 months following inclusion in the study. The dose of corticosteroid considered immunosuppressive is the equivalent of prednisone at a dose of 20 mg/day, for adults, for 14 days (cumulative dose equivalent to at least 280 mg of prednisone). Continuous use of topical or nasal corticosteroid is not considered immunosuppressive;
- Having received blood products (transfusions or immunoglobulins) in the last three months prior to inclusion in the study, or scheduled administration of blood products or immunoglobulin in the 12 months following inclusion in the study;
- Fever, suspected or measured, in the 72 hours prior to vaccination or axillary temperature ≥ 37.8°C on the day of vaccination (inclusion may be postponed until the potential participant has been fever-free for 72 hours);
- Having received a live attenuated virus vaccine in the last 28 days or an inactivated vaccine in the last 14 days prior to inclusion in the study, or having been immunized within 12 months of inclusion in the study;
- Any other condition that, in the opinion of the principal investigator or his/her medical representative, may jeopardize the safety or rights of a potential participant or that prevents him/her from complying with this protocol.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Brazil5 sites, 5 recruiting
- Recruiting
CWB 02 - Centro Médico São Francisco
Curitiba, Paraná, 80810-050
Clóvis A Cunha, PhD, +55(41)3019-5552, arnscunha@gmail.com
- Recruiting
PET 01 - Hospital Escola da Universidade de Pelotas - HEUFPEL
Pelotas, Rio Grande do Sul, 96040-010
Danise S Oliveira, PhD, +55(53)98133-4454, danise.oliveira@gmail.com
- Recruiting
POA 05 - Núcleo de Pesquisa do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, 90430-001
Marcela S Biernat, PhD, +55(51) 3519-5226, marcelab.santiago@gmail.com
- Recruiting
POA 02 - Associação Hospitalar Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90560-032
Ernesto Gewehr Filho, PhD, +55(51)3327-7150, paulo.gewehr@hmv.org.br
- Recruiting
POA 01 - Centro de Pesquisa: Hospital São Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
Fabiano Ramos, MD PhD, +55 (51) 3320-5610, framos@pucrs.br
About this study
Official title: Phase 3B, Double-blind, Randomized Study to Evaluate the Safety and Non-inferiority of the Humoral Immune Response of the Butantan Dengue Vaccine in Participants Aged 60 to 79 Years Compared to Participants Aged 40 to 59 Years
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.
Read the detailed description
The study aims to evaluate the non-inferiority of the immune response induced by the Dengue 1,2,3,4 (attenuated) vaccine in participants aged 60 - 79 years old (elderly) compared to participants aged 40 to 59 years on Day 42 + 7 days after vaccination. The primary analysis will include the immunogenicity cohort (n=460 participants, allocated 1:1). The primary outcome is the proportion of neutralizing antibody seroconversion measured by plaque reduction neutralization test (PRNT50), for each dengue serotype, of participants aged 60 - 79 years (elderly) compared with participants aged 40 to 59 years (adults), with or without previous exposure to dengue, on Day 42 + 7 days after vaccination. The primary safety outcome will be the frequency and intensity of solicited and unsolicited adverse reactions from vaccination to Day 22 post-vaccination among participants aged 60 - 79 years and in participants aged 40 to 59 years, with or without prior exposure to dengue. The study will last one year in order to assess the duration of the immune response and serious adverse events (SAE) and events of special interest (SIAE). Throughout the study period, there will be surveillance of suspected and confirmed cases of dengue, chikungunya fever and Zika virus fever. Therefore, if the null hypothesis is rejected, the immunogenicity and safety results of immunobridging will be used to expand the use of Dengue 1,2,3,4 (attenuated) for the age group of 60 - 79 years old.
- Conditions
- Dengue
- Being tested
- Dengue 1,2,3,4 (attenuated) vaccine
- Keywords
- dengue vaccine, elderly population
- Medical subject headings
- Dengue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dengue 1,2,3,4 (attenuated) vaccineBiological
Each 0.5 mL dose of the lyophilized formulation of Dengue 1,2,3,4 (attenuated) presents an approximate concentration of 103.0 PFU of each vaccine virus rDEN1Δ30-1545, rDEN2/4Δ30(ME)-1495,7163, rDEN3Δ30/31-7164, rDEN4Δ30-7132,7163,8308.
| Study group | Role | What they receive |
|---|---|---|
| Dengue 1,2,3,4 (attenuated) vaccine in a single dose older adult | Experimental | Participants (60-79y) receiving Butantan DV (N=690) Receives: Biological: Dengue 1,2,3,4 (attenuated) vaccine |
| Dengue 1,2,3,4 (attenuated) vaccine in a single dose adult | Experimental | Participants (40-59y) receiving Butantan DV (N=230) Receives: Biological: Dengue 1,2,3,4 (attenuated) vaccine |
| Placebo | Placebo comparator | Participants (60-79y) receiving Placebo (N=77) Receives: Biological: Dengue 1,2,3,4 (attenuated) vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immunogenicity Primary
Proportion of neutralizing antibody seroconversion measured by PRNT50, for each dengue serotype, of participants aged 60 -79 years compared (elderly) with participants aged 40 to 59 years (adults), with or without previous exposure to dengue, on Day 42 + 7 days after vaccination.
Measured: Day 42+7 days post-vaccination.
Safety Primary 1.
Frequency and intensity of vaccine-related solicited (local and systemic) adverse events, from vaccination to Day 22 + 3 days post-vaccination, among participants aged 60 - 79 years and in participants aged 40 to 59 years, with or without previous exposure to dengue.
Measured: From vaccination to Day 22 + 3 days post-vaccination.
Safety Primary 2.
Frequency and intensity of vaccine-related unsolicited adverse events, from vaccination to Day 22 + 3 days post-vaccination, in participants aged 60-79 years and in participants aged 40 to 59 years, with or without previous exposure to dengue.
Measured: From vaccination to Day 22 + 3 days post-vaccination.
Secondary outcomes (10)
Immunogenicity Secondary 1.
GMT of neutralizing antibodies, for each dengue serotype, of participants aged 60-79 years and of participants aged 40 to 59 years, with or without previous exposure to dengue, on Day 1, Day 42 + 7 days and Day 364 + 28 days after vaccination.
Measured: Day 1, Day 42 + 7 days and Day 364 + 28 days after vaccination.
Immunogenicity Secondary 2.
GMT ratio of neutralizing antibodies, for each dengue serotype, of participants aged 60-79 years compared with participants aged 40 to 59 years, with or without previous exposure to dengue, on Day 42 + 7 days after vaccination.
Measured: Day 42 + 7 days after vaccination.
Immunogenicity Secondary 3.
GMT ratio of neutralizing antibodies, for each dengue serotype, of participants aged 60-79 years compared with participants aged 40 to 59 years, with or without previous exposure to dengue, on Day 364 + 28 days after vaccination.
Measured: Day 364 + 28 days after vaccination.
Immunogenicity Secondary 4.
Valence or seropositivity rate for multiple dengue virus serotypes measured by PRNT50 in participants aged 60-79 years and in participants aged 40 to 59 years, with or without previous exposure to dengue, on Days 42 + 7 days and Day 364 + 28 days after vaccination.
Measured: Days 42 + 7 days and Day 364 + 28 days after vaccination.
Safety Secondary 1.
Frequency and intensity of unsolicited adverse reactions, from Day 22 + 3 days post-vaccination until the end of study follow-up, in elderly participants (60-79 years) and adults (40-59 years), with or without previous exposure to dengue.
Measured: From Day 22 + 3 days post-vaccination until the end of study.
Safety Secondary 2.
Frequency, intensity and causality of serious adverse events, in elderly participants (60-79 years) and adults (40-59 years), with or without previous exposure to dengue, throughout the study period.
Measured: Throughout the study period.
Safety Secondary 3.
Frequency, intensity and causality of adverse events of special interest, in elderly participants (60-79 years) and adults (40-59 years), with or without previous exposure to dengue, throughout the study period.
Measured: Throughout the study period.
Safety Secondary 4.
Frequency of viremia after vaccination at visits on Days 1, 6, 9, 12, 22 and 30 and laboratory abnormalities in a cohort of 56 elderly participants (60-79 years).
Measured: Days 1, 6, 9, 12, 22 and 30.
Safety Secondary 5.
Frequency of cases of symptomatic vaccine viremia (Day 29) and of virologically confirmed cases of dengue (VCD), chikungunya fever and Zika virus fever in elderly individuals (60-79 years) and adults (40-59 years), throughout the study period.
Measured: Day 29 and throughout the study period.
Safety Secondary 6.
Frequency of laboratory alterations (aspartate aminotransferase, alanine aminotransferase, total bilirubin, creatinine, blood count) grade 2 or higher among elderly (60-79 years) and adults (40-59 years) on Day 22 + 3 days after vaccination.
Measured: Day 22 + 3 days after vaccination.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2025
- Study start3 Mar 2026
- Primary completionMar 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for DengueStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized, double-blind (60-79 years old) 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. The 997 participants will be randomized with a 9:3:1 allocation, so that the largest group (60 - 79 years) will be allocated to receive Dengue 1,2,3,4 (attenuated) in a blinded regimen (n=690), the next group (40-59 years) will be allocated to receive Dengue 1,2,3,4 (attenuated) in an open regimen (n=230) and the last (60-79 years) will be allocated to receive placebo (n=77), respectively.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 997 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Butantan Institute
- Sponsor type
- Other government
- Collaborators
- Butantan Foundation
- Responsible party
- Sponsor
- Investigators
- Fernanda C Boulos, MD, PhD, Study director, Instituto Butantan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06891950
- Sponsor's protocol ID
- DEN-04-IB
- Acronym
- DEN-04-IB
- Status last verified
- Jul 2026
- First submitted
- 18 Mar 2025
- Last updated
- 16 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev. 1998 Jul;11(3):480-96. doi: 10.1128/CMR.11.3.480.
PubMed 9665979Laydon 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.
PubMed 34219653Patel 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.
PubMed 35639602Blaney 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.
PubMed 16553547Kallas 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.
PubMed 32220283Kallas 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.
PubMed 38294972Chiaravalloti-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.
PubMed 31109295Schneider 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.
PubMed 37321235Casey 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.
PubMed 29443626Hou 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.
PubMed 38600250Weinberg 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.
PubMed 20170376Levin 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.
PubMed 18419349Collier 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.
PubMed 34192737Hanley 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.
PubMed 6827763Musso 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.
PubMed 31597021
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3B, Double-blind, Randomized Study to Evaluate the Safety and Non-inferiority of the Humoral Immune Response of the Butantan Dengue Vaccine in Participants Aged 60 to 79 Years Compared to Participants Aged 40 to 59 Years
- ClinicalTrials.gov ID
- NCT06891950
- Acronym / sponsor ID
- DEN-04-IB / DEN-04-IB
- Conditions
- Dengue
- Keywords
- dengue vaccine, elderly population
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 997 participants (estimated)
- Lead sponsor
- Butantan InstituteOther government
- Collaborators
- Butantan Foundation
- Study start
- 3 Mar 2026 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 24 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study aims to evaluate the non-inferiority of the immune response induced by the Dengue 1,2,3,4 (attenuated) vaccine in participants aged 60 - 79 years old (elderly) compared to participants aged 40 to 59 years on Day 42 + 7 days after vaccination. The primary analysis will include the immunogenicity cohort (n=460 participants, allocated 1:1). The primary outcome is the proportion of neutralizing antibody seroconversion measured by plaque reduction neutralization test (PRNT50), for each dengue serotype, of participants aged 60 - 79 years (elderly) compared with participants aged 40 to 59 years (adults), with or without previous exposure to dengue, on Day 42 + 7 days after vaccination. The primary safety outcome will be the frequency and intensity of solicited and unsolicited adverse reactions from vaccination to Day 22 post-vaccination among participants aged 60 - 79 years and in participants aged 40 to 59 years, with or without prior exposure to dengue. The study will last one year in order to assess the duration of the immune response and serious adverse events (SAE) and events of special interest (SIAE). Throughout the study period, there will be surveillance of suspected and confirmed cases of dengue, chikungunya fever and Zika virus fever. Therefore, if the null hypothesis is rejected, the immunogenicity and safety results of immunobridging will be used to expand the use of Dengue 1,2,3,4 (attenuated) for the age group of 60 - 79 years old.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- This is a randomized, double-blind (60-79 years old) 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. The 997 participants will be randomized with a 9:3:1 allocation, so that the largest group (60 - 79 years) will be allocated to receive Dengue 1,2,3,4 (attenuated) in a blinded regimen (n=690), the next group (40-59 years) will be allocated to receive Dengue 1,2,3,4 (attenuated) in an open regimen (n=230) and the last (60-79 years) will be allocated to receive placebo (n=77), respectively.
| Arm | Type | Receives |
|---|---|---|
| Dengue 1,2,3,4 (attenuated) vaccine in a single dose older adult | Experimental | Biological: Dengue 1,2,3,4 (attenuated) vaccineParticipants (60-79y) receiving Butantan DV (N=690) |
| Dengue 1,2,3,4 (attenuated) vaccine in a single dose adult | Experimental | Biological: Dengue 1,2,3,4 (attenuated) vaccineParticipants (40-59y) receiving Butantan DV (N=230) |
| Placebo | Placebo comparator | Biological: Dengue 1,2,3,4 (attenuated) vaccineParticipants (60-79y) receiving Placebo (N=77) |
Who may qualify
- Ages
- 40 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- a. Healthy participants aged between 40 and 79 years at the time of study entry, with or without a history of exposure to dengue fever;
Key exclusion criteria (16 listed)
- a. For female participants with reproductive potential: pregnancy (confirmed by positive β-hCG test), breastfeeding or manifest intention to have sexual practices with reproductive potential without using a contraceptive method in the 90 days following vaccination;
- l.Having received an immunosuppressive dose of corticosteroid in the last three months prior to inclusion in the study or administration of an immunosuppressive dose of corticosteroid for the 12 months following inclusion in the study. The dose of corticosteroid considered immunosuppressive is the equivalent of prednisone at a dose of 20 mg/day, for adults, for 14 days (cumulative dose equivalent to at least 280 mg of prednisone). Continuous use of topical or nasal corticosteroid is not considered immunosuppressive;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dengue 1,2,3,4 (attenuated) vaccineEach 0.5 mL dose of the lyophilized formulation of Dengue 1,2,3,4 (attenuated) presents an approximate concentration of 103.0 PFU of each vaccine virus rDEN1Δ30-1545, rDEN2/4Δ30(ME)-1495,7163, rDEN3Δ30/31-7164, rDEN4Δ30-7132,7163,8308. | Biological | Dengue 1,2,3,4 (attenuated) vaccine in a single dose adult, Dengue 1,2,3,4 (attenuated) vaccine in a single dose older adult, Placebo |
Primary outcome
Immunogenicity Primary
Time frame: Day 42+7 days post-vaccination.
Proportion of neutralizing antibody seroconversion measured by PRNT50, for each dengue serotype, of participants aged 60 -79 years compared (elderly) with participants aged 40 to 59 years (adults), with or without previous exposure to dengue, on Day 42 + 7 days after vaccination.
Safety Primary 1.
Time frame: From vaccination to Day 22 + 3 days post-vaccination.
Frequency and intensity of vaccine-related solicited (local and systemic) adverse events, from vaccination to Day 22 + 3 days post-vaccination, among participants aged 60 - 79 years and in participants aged 40 to 59 years, with or without previous exposure to dengue.
Safety Primary 2.
Time frame: From vaccination to Day 22 + 3 days post-vaccination.
Frequency and intensity of vaccine-related unsolicited adverse events, from vaccination to Day 22 + 3 days post-vaccination, in participants aged 60-79 years and in participants aged 40 to 59 years, with or without previous exposure to dengue.
10 secondary outcomes
Immunogenicity Secondary 1.
Time frame: Day 1, Day 42 + 7 days and Day 364 + 28 days after vaccination.
Immunogenicity Secondary 2.
Time frame: Day 42 + 7 days after vaccination.
Immunogenicity Secondary 3.
Time frame: Day 364 + 28 days after vaccination.
Immunogenicity Secondary 4.
Time frame: Days 42 + 7 days and Day 364 + 28 days after vaccination.
Safety Secondary 1.
Time frame: From Day 22 + 3 days post-vaccination until the end of study.
Safety Secondary 2.
Time frame: Throughout the study period.
Safety Secondary 3.
Time frame: Throughout the study period.
Safety Secondary 4.
Time frame: Days 1, 6, 9, 12, 22 and 30.
Safety Secondary 5.
Time frame: Day 29 and throughout the study period.
Safety Secondary 6.
Time frame: Day 22 + 3 days after vaccination.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2026.
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- Background: PubMed 32220283Kallas 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: PubMed 38294972Kallas 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: PubMed 31109295Chiaravalloti-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: PubMed 37321235Schneider 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fernanda C Boulos, MD, PhD study director
Instituto Butantan
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dengue 1,2,3,4 (attenuated) vaccine in people with Dengue, run by Butantan Institute at 5 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fabiano Ramos, MD, PhD (+55(51) 3320-5610, framos@pucrs.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immunogenicity Primary (time frame: Day 42+7 days post-vaccination.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06891950, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2026; AzTrials last refreshed its copy on 26 Oct 2026.