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

March 5, 2026 updated by: Butantan Institute

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

997

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Fabiano Ramos, MD, PhD
  • Phone Number: +55(51) 3320-5610
  • Email: framos@pucrs.br

Study Locations

  • Brazil
    • Paraná
      • Curitiba, Paraná, Brazil, 80810-050
        • Recruiting
        • CWB 02 - Centro Médico São Francisco
        • Contact:
    • Rio Grande do Sul
      • Pelotas, Rio Grande do Sul, Brazil, 96040-010
        • Recruiting
        • PET 01 - Hospital Escola da Universidade de Pelotas - HEUFPEL
        • Contact:
      • Porto Alegre, Rio Grande do Sul, Brazil, 90430-001
        • Recruiting
        • POA 05 - Núcleo de Pesquisa do Rio Grande do Sul
        • Contact:
      • Porto Alegre, Rio Grande do Sul, Brazil, 90560-032
        • Recruiting
        • POA 02 - Associação Hospitalar Moinhos de Vento
        • Contact:
      • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
        • Recruiting
        • POA 01 - Centro de Pesquisa: Hospital São Lucas - PUCRS
        • Contact:
          • Fabiano Ramos, MD PhD
          • Phone Number: +55 (51) 3320-5610
          • Email: framos@pucrs.br

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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;

    b. Agree to periodic contact by telephone, electronic means, and home visits and to the research center;

    c. 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;

    d. 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.

Exclusion Criteria:

  • 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;

    b. Planned donation of blood, semen or eggs in the 90 days following vaccination;

    c. Evidence of active uncontrolled neurological, cardiac, pulmonary, hepatic or renal disease according to anamnesis or physical examination, at the discretion of the investigator;

    d. 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;

    e. 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;

    f. 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;

    g. History of severe allergic reaction or anaphylaxis to the vaccine or components of the study vaccine;

    h. History of asplenia;

    i. 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;

    j. Previous participation in a dengue vaccine evaluation study or previous exposure to dengue vaccine;

    k. 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;

    m. 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;

    n. 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);

    o. 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;

    p. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dengue 1,2,3,4 (attenuated) vaccine in a single dose older adult
Participants (60-79y) receiving Butantan DV (N=690)
Biological: Dengue 1,2,3,4 (attenuated) vaccine
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.
Experimental: Dengue 1,2,3,4 (attenuated) vaccine in a single dose adult
Participants (40-59y) receiving Butantan DV (N=230)
Biological: Dengue 1,2,3,4 (attenuated) vaccine
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.
Placebo Comparator: Placebo
Participants (60-79y) receiving Placebo (N=77)
Biological: Dengue 1,2,3,4 (attenuated) vaccine
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Day 42+7 days post-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.
From vaccination to Day 22 + 3 days post-vaccination.
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.
From vaccination to Day 22 + 3 days post-vaccination.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immunogenicity Secondary 1.
Time Frame: Day 1, Day 42 + 7 days and Day 364 + 28 days after vaccination.
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.
Day 1, Day 42 + 7 days and Day 364 + 28 days after vaccination.
Immunogenicity Secondary 2.
Time Frame: Day 42 + 7 days after vaccination.
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.
Day 42 + 7 days after vaccination.
Immunogenicity Secondary 3.
Time Frame: Day 364 + 28 days after vaccination.
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.
Day 364 + 28 days after vaccination.
Immunogenicity Secondary 4.
Time Frame: Days 42 + 7 days and Day 364 + 28 days after vaccination.
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.
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.
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.
From Day 22 + 3 days post-vaccination until the end of study.
Safety Secondary 2.
Time Frame: Throughout the study period.
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.
Throughout the study period.
Safety Secondary 3.
Time Frame: Throughout the study period.
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.
Throughout the study period.
Safety Secondary 4.
Time Frame: Days 1, 6, 9, 12, 22 and 30.
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).
Days 1, 6, 9, 12, 22 and 30.
Safety Secondary 5.
Time Frame: Day 29 and throughout the study period.
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.
Day 29 and throughout the study period.
Safety Secondary 6.
Time Frame: Day 22 + 3 days after vaccination.
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.
Day 22 + 3 days after vaccination.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Butantan Institute

Collaborators

Fundação Butantan

Investigators

  • Study Director: Fernanda C Boulos, MD, PhD, Instituto butantan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 3, 2026

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

March 18, 2025

First Submitted That Met QC Criteria

March 21, 2025

First Posted (Actual)

March 24, 2025

Study Record Updates

Last Update Posted (Actual)

March 6, 2026

Last Update Submitted That Met QC Criteria

March 5, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DEN-04-IB

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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