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Phase III Trial to Evaluate Efficacy and Safety of a Tetravalent Dengue Vaccine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02406729
Recruitment Status : Active, not recruiting
First Posted : April 2, 2015
Last Update Posted : February 4, 2021
Information provided by (Responsible Party):
Butantan Institute

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Dengue Biological: Dengue 1,2,3,4 (attenuated) vaccine Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16944 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase III Trial to Evaluate Efficacy and Safety of a Dengue 1,2,3,4 (Attenuated) Vaccine
Actual Study Start Date : February 2016
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dengue Safety Vaccines

Arm Intervention/treatment
Experimental: Dengue 1,2,3,4 (attenuated) vaccine
Dengue 1,2,3,4 (attenuated) vaccine Single dose, SC
Biological: Dengue 1,2,3,4 (attenuated) vaccine
Dose 1000 PFU per virus (1,2,3,4) Route:subcutaneous
Other Names:
  • Butantan DV
  • TetraVax-DV-TV003

Placebo Comparator: Placebo
Placebo Single dose, SC
Other: Placebo

Primary Outcome Measures :
  1. Efficacy (incidence density of symptomatic dengue cases, virologically confirmed) [ Time Frame: at 52 weeks 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.

  2. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   24 Months to 59 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. Children who have completed 24 months of age, adolescents and adults who have not completed 60 years of age;
  2. Agree with periodic contacts, either/or by phone, electronic means, and home visits.
  3. Show voluntary intention to participate in the study, documented by the participant's or participant's legal representative's signature of the informed consent form.

Exclusion Criteria:

  1. For women: Pregnancy (confirmed by positive beta-hCG test) or breastfeeding;
  2. Evidence of active neurological, cardiac, pulmonary, hepatic or renal disease as per clinical history and/or physical examination;
  3. Compromised immune system diseases including: decompensated diabetes mellitus, cancer (except basal cell carcinoma), congenital or acquired immune deficiencies and not controlled autoimmune, as per clinical history and/or physical examination;
  4. Behavioral, cognitive or psychiatric disease that in the opinion of the principal investigator or his representative physician, affects the participant ability to understand and cooperate with all study protocol requirements;
  5. Abusive usage of alcohol or drugs in the past 12 months that has caused medical, professional or family problems, indicated by clinical history;
  6. History of severe allergic reactions or anaphylaxis to the vaccine or to components of the vaccine in study;
  7. History of asplenia;
  8. Use of any investigational product within 28 days before or after receiving this study vaccination;
  9. Has participated in another clinical trial six months prior to inclusion in the study or planning to participate in another clinical trial within 2 years following inclusion;
  10. Use of immunosuppressant drugs such as: antineoplastic chemotherapy, radiation therapy, immunosuppressants to induce tolerance to transplants, and corticosteroids use (except topical or nasal). For this protocol will be considered for exclusion use of corticosteroids 3 months prior to the inclusion in the study and 6 months prior to the inclusion for the other therapies mentioned, and planned use of any immunosuppressant therapy within 2 years following inclusion in the study. It will be considered immunosuppressive dose of corticosteroids the equivalent to a dose ≥20 mg of prednisone per day for adults and the equivalent of prednisone at 2 mg/kg/day for children for over 7 days;
  11. Have received blood products in the past three months, including transfusions or immunoglobulin, or scheduled administration of blood products or immunoglobulin for the following 2 years after vaccination;
  12. Fever or suspected fever within 72 hours prior to vaccination or axillary temperature greater than 37,8°C on the day of vaccination (inclusion might be postponed until participant has completed 72 hours of no fever);
  13. Have received live virus vaccine within 28 days or killed virus vaccine in the last 14 days prior to vaccination, or have a scheduled immunization during the first 28 days after receiving the investigational product;
  14. Any other condition that might put in risk the safety/rights of a potential participant or hurdle his/her compliance with this protocol in investigator's opinion or his representative physician.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02406729

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Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
Manaus, Amazonas, Brazil, 69040-000
Instituto Gonçalo Muniz - Fiocruz Bahia
Simões Filho, BA, Brazil, 43700-000
Universidade Federal do Ceará
Fortaleza, CE, Brazil, 60430-160
Universidade de Brasília
Brasilia, DF, Brazil, 71691-082
Universidade Federal de Minas Gerais
Belo Horizonte, MG, Brazil, 30750-140
Hospital Universitário Júlio Müller da Universidade Federal de Mato Grosso
Cuiabá, Mount, Brazil, 78048-610
Universidade Federal de Mato Grosso do Sul
Campo Grande, MS, Brazil, 79070-900
Centro de Pesquisas Aggeu Magalhães - Fiocruz Pernambuco
Recife, Pernambuco, Brazil, 50740-465
Universidade Federal de Roraima - UFRR
Boa Vista, Roraima, Brazil, 69304-000
Centro de Pesquisas em Medicina Tropical de Rondônia (CEPEM)
Porto Velho, RO, Brazil, 78918-791
Hospital São Lucas da Pontificia Universidade Catolica do Rio Grande do Sul
Porto Alegre, RS, Brazil, 90619-900
Universidade Federal de Sergipe
Laranjeiras, SE, Brazil, 49170-000
Santa Casa de Misericórdia de São Paulo - CSEBF
São Paulo, SP, Brazil, 01133-020
Faculdade de Medicina de São José do Rio Preto - FAMERP
São José Do Rio Preto, São Paulo, Brazil, 15090-000
Instituto de Infectologia Evandro Chagas - Fiocruz
Rio De Janeiro, Brazil, 21710-232
São Paulo, Brazil, 05403-000
Sponsors and Collaborators
Butantan Institute
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Study Director: Ricardo Palacios, MD, PhD Butantan Institute
Principal Investigator: Esper G Kallas, MD, PhD School of Medicine, University of São Paulo
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Responsible Party: Butantan Institute Identifier: NCT02406729    
Other Study ID Numbers: DEN-03-IB
U1111-1168-8679 ( Registry Identifier: UTN )
First Posted: April 2, 2015    Key Record Dates
Last Update Posted: February 4, 2021
Last Verified: February 2021
Additional relevant MeSH terms:
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Arbovirus Infections
Vector Borne Diseases
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral