NCT02406729

Phase III, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy, Safety, and Immunogenicity of the Dengue 1, 2, 3, 4 (Attenuated) Vaccine From Instituto Butantan

Status unknown Phase 3 Last updated 14 February 2024

What this trial tests

Phase 3 trial testing Dengue 1,2,3,4 (attenuated) vaccine in Dengue in 16,935 participants. Status unknown.

Timeline

22 February 2016

Primary endpoint
13 July 2021

1 November 2024

Quick facts

Lead sponsor	Butantan Institute
Phase	Phase 3
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	single group
Masking	quadruple
Primary purpose	prevention
Enrollment	16,935
Start date	22 February 2016
Primary completion	13 July 2021
Estimated completion	1 November 2024
Sites	17 locations across Brazil

Drugs / interventions tested

• Dengue 1,2,3,4 (attenuated) vaccine — full drug profile →
• Placebo

Conditions studied

• Dengue — all drugs for Dengue →

Sponsor

Butantan Institute

Who can join

Adults 24 Months to 59, any sex, with Dengue. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Efficacy (incidence density of symptomatic dengue cases, virologically confirmed)
  Time frame: Five years post vaccination, all cases after 28 days post-vaccination
  The primary efficacy outcome is incidence density of symptomatic dengue cases, virologically confirmed, after 28 days post-vaccination. Virological confirmation might be done by viral isolation, RT-PCR and/or detection of NS1.
• Safety (adverse reactions)
  Time frame: In the first 21 days post-vaccination
  The primary safety outcome is the frequency of local and systemic adverse reactions, solicited and non-solicited in the three age groups, within the first 21 days post-vaccination. Adverse reactions are defined as adverse events that have a reasonable causal relationship with vaccination.

Sponsor's own description

This is a randomized, multicenter, double-blind, placebo-controlled Phase III study that will evaluate efficacy and safety of a live attenuated, tetravalent, lyophilized dengue vaccine produced by Butantan Institute.

The study will be carried out in multiple sites in Brazil. The study will be community-based in select urban areas where there's dengue transmission.

Study's intervention will be a single dose of the tetravalent dengue vaccine or placebo in a ratio 2:1. For efficacy analysis will be considered all dengue cases occurring after 28 days post-vaccination in the entire population of 16944 participants.

For safety analysis participants will be divided in three age groups: 18 to 59 ys, 7-17 ys and 2 to 6 ys. In each of these age groups there will be a minimum of 4992 participants. The age groups of 18 to 59 ys and 7 to 17 ys will start first. Once safety data for the first 21 days after vaccination is analysed for 450 participants in 7-to17-ys age group, the following group, of 2 to 6 ys, will start.

The study's hypothesis is that the vaccine under investigation and produced by Butantan Institute is safe and provides protection against dengue symptomatic disease of 80% or more with a lower bound of the 95% confidence interval of 25%. This way, the expected number of dengue cases virologically confirmed is 24 or more which will provide a response in terms of vaccine efficacy.

All participants will be followed up for five years to verify dengue incidence, regardless severity.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. A review of Dengvaxia®: development to deployment.
   Thomas SJ, Yoon IK. · · 2019 · cited 223× · PMID 31589551 · DOI 10.1080/21645515.2019.1658503
2. Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults.
   Kallás EG, Cintra MAT, Moreira JA, Patiño EG, et al · · 2024 · cited 127× · PMID 38294972 · DOI 10.1056/nejmoa2301790
3. Viral Emerging Diseases: Challenges in Developing Vaccination Strategies.
   Trovato M, Sartorius R, D'Apice L, Manco R, et al · · 2020 · cited 87× · PMID 33013898 · DOI 10.3389/fimmu.2020.02130
4. Twenty Years of Progress Toward West Nile Virus Vaccine Development.
   Kaiser JA, Barrett ADT. · · 2019 · cited 63× · PMID 31491885 · DOI 10.3390/v11090823
5. Current Development and Challenges of Tetravalent Live-Attenuated Dengue Vaccines.
   Hou J, Ye W, Chen J. · · 2022 · cited 46× · PMID 35281026 · DOI 10.3389/fimmu.2022.840104
6. Anti-dengue Vaccines: From Development to Clinical Trials.
   Pinheiro-Michelsen JR, Souza RDSO, Santana IVR, da Silva PS, et al · · 2020 · cited 37× · PMID 32655561 · DOI 10.3389/fimmu.2020.01252
7. 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.
   Nogueira ML, Cintra MAT, Moreira JA, Patiño EG, et al · · 2024 · cited 34× · PMID 39116904 · DOI 10.1016/s1473-3099(24)00376-1
8. Controlled Human Infection Models To Accelerate Vaccine Development.
   Choy RKM, Bourgeois AL, Ockenhouse CF, Walker RI, et al · · 2022 · cited 33× · PMID 35862754 · DOI 10.1128/cmr.00008-21