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

NCT ID: NCT02406729

Last Updated: 2024-02-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 16935 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-22
• Study Completion Date: 2024-11-30

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.

Conditions

Dengue

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Dengue 1,2,3,4 (attenuated) vaccine

Dengue 1,2,3,4 (attenuated) vaccine Single dose, SC

Group Type: EXPERIMENTAL

Dengue 1,2,3,4 (attenuated) vaccine

Intervention Type: BIOLOGICAL

Dose 1000 PFU per virus (1,2,3,4) Route:subcutaneous

Placebo

Placebo Single dose, SC

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Route:subcutaneous

Interventions

Dengue 1,2,3,4 (attenuated) vaccine

Dose 1000 PFU per virus (1,2,3,4) Route:subcutaneous

Intervention Type: BIOLOGICAL

Placebo

Route:subcutaneous

Intervention Type: OTHER

Other Intervention Names

Butantan DV; TetraVax-DV-TV003

Eligibility Criteria

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.

• Minimum Eligible Age: 24 Months
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Butantan Institute

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fernanda C Boulos, MD, PhD

Role: STUDY_DIRECTOR

Instituto Butantan

Locations

Fundação de Medicina Tropical Doutor Heitor Vieira Dourado

Manaus, Amazonas, Brazil

Universidade Federal do Ceará

Fortaleza, Ceará, Brazil

Instituto Gonçalo Muniz - Fiocruz Bahia

Simões Filho, Estado de Bahia, Brazil

Universidade de Brasília

Brasília, Federal District, Brazil

Universidade Federal de Mato Grosso do Sul

Campo Grande, Mato Grosso do Sul, Brazil

Universidade Federal de Minas Gerais

Belo Horizonte, Minas Gerais, Brazil

Hospital Universitário Júlio Müller da Universidade Federal de Mato Grosso

Cuiabá, Mount, Brazil

Centro de Pesquisas Aggeu Magalhães - Fiocruz Pernambuco

Recife, Pernambuco, Brazil

Hospital Escola da Universidade Federal de Pelotas (HEUFPel)

Pelotas, Rio Grande do Sul, Brazil

Hospital São Lucas da Pontificia Universidade Catolica do Rio Grande do Sul

Porto Alegre, Rio Grande do Sul, Brazil

Centro de Pesquisas em Medicina Tropical de Rondônia (CEPEM)

Porto Velho, Rondônia, Brazil

Universidade Federal de Roraima - UFRR

Boa Vista, Roraima, Brazil

Universidade Federal de Sergipe

Laranjeiras, Sergipe, Brazil

Faculdade de Medicina de São José do Rio Preto - FAMERP

São José do Rio Preto, São Paulo, Brazil

Santa Casa de Misericórdia de São Paulo - CSEBF

São Paulo, São Paulo, Brazil

Instituto de Infectologia Evandro Chagas - Fiocruz

Rio de Janeiro, , Brazil

HCFMUSP

São Paulo, , Brazil

Countries

Brazil

References

Precioso AR, Palacios R, Thome B, Mondini G, Braga P, Kalil J. Clinical evaluation strategies for a live attenuated tetravalent dengue vaccine. Vaccine. 2015 Dec 10;33(50):7121-5. doi: 10.1016/j.vaccine.2015.09.105. Epub 2015 Oct 14.

Reference Type: BACKGROUND

PMID: 26458796 (View on PubMed)

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 Oct 14;66:127836. doi: 10.1016/j.vaccine.2025.127836. Online ahead of print.

Reference Type: DERIVED

PMID: 41092804 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39116904 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38294972 (View on PubMed)

Other Identifiers

U1111-1168-8679

Identifier Type: REGISTRY

Identifier Source: secondary_id

DEN-03-IB

Identifier Type: -

Identifier Source: org_study_id