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This randomized, controlled, double blind trial aims at assessing the safety and immunogenicity profiles of the co-administered Live Attenuated Dengue and Chikungunya vaccines comparatively to the isolated administration, in the adult population aged 18 to 59 years without prior exposure to either arbovirus.
A Phase 3b multicenter, randomized, controlled, double-blind clinical trial was designed to evaluate the Immunogenicity (non-inferiority), 28 days post-immunization, for each Dengue and Chikungunya serotypes, as well as the safety, 21 days post-immunization, of the co-administration of the live attenuated Dengue and Chikungunya vaccines compared to the separate administration in adults aged 18 to 59 years without prior exposure to either arbovirus.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dengue and Chikungunya vaccines co-administered | Experimental | A single dose of Butantan-DV + a single dose of VLA1555, administered concomitantly in opposite arms on Day 1. |
|
| Dengue vaccine only | Experimental | A single dose of Butantan-DV + placebo, administered concomitantly in opposite arms on Day 1. |
|
| Chikungunya vaccine only | Experimental | A single dose of VLA1555 + placebo, administered concomitantly in opposite arms on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DENGUE: Dengue 1,2,3,4 (attenuated) vaccine CHIKUNGUNYA: Chikungunya (CHIKV) live attenuated vaccine (VLA1555) | Biological | DENGUE: Dose 10^2.5-4.1 PFU per virus (1,2,3,4) Route: Subcutaneous CHIKUNGUNYA: Dose >= 3.0 log TCID50 per 0.5 mL Route: Intramuscular |
| Measure | Description | Time Frame |
|---|---|---|
| Immunogenicity Primary | Demonstrate the non-inferiority of the antibody response of co-administered Dengue and Chikungunya vaccines compared to Dengue and Chikungunya vaccines administered separately, for each Dengue serotype and Chikungunya in the adult population aged 18 to 59 years without prior exposure to either arbovirus, by calculating the Geometric Mean Titer (GMT) and the GMT ratio, post-immunization for each dengue serotype and chikungunya, across all intervention groups. | 28 days post-immunization |
| Safety Primary | Assess the safety profile of co-administered Dengue and Chikungunya vaccines and Dengue and Chikungunya vaccines administered separately, in the adult population aged 18 to 59 years without prior exposure to either arbovirus, through the frequency of participants with solicited (local and systemic) and unsolicited adverse events (AEs), in all intervention groups. | 21 days post-immunization |
| Measure | Description | Time Frame |
|---|---|---|
| Immunogenicity Secondary 1 | Assess the antibody response of co-administered Dengue and Chikungunya vaccines compared to Dengue and Chikungunya vaccines administered separately, in adults aged 18 to 59 years without prior exposure to either arbovirus, comparing the seroconversion rates, for each dengue serotype and chikungunya, across all intervention groups. | 28 days post-immunization |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Clóvis Arns da Cunha, MD, PhD | Contact | +55 (41) 99828-8444 | arnscunha@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centro Médico de São Francisco | Curitiba | Paraná | 80810-050 | Brazil | ||
| Centro de Pesquisa Inova |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37039318 | Background | Bonanni P, Steffen R, Schelling J, Balaisyte-Jazone L, Posiuniene I, Zatonski M, Van Damme P. Vaccine co-administration in adults: An effective way to improve vaccination coverage. Hum Vaccin Immunother. 2023 Dec 31;19(1):2195786. doi: 10.1080/21645515.2023.2195786. Epub 2023 Apr 11. | |
| 32497524 | Result | Wressnigg N, Hochreiter R, Zoihsl O, Fritzer A, Bezay N, Klingler A, Lingnau K, Schneider M, Lundberg U, Meinke A, Larcher-Senn J, Corbic-Ramljak I, Eder-Lingelbach S, Dubischar K, Bender W. Single-shot live-attenuated chikungunya vaccine in healthy adults: a phase 1, randomised controlled trial. Lancet Infect Dis. 2020 Oct;20(10):1193-1203. doi: 10.1016/S1473-3099(20)30238-3. Epub 2020 Jun 1. |
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Phase 3b Multicenter, Randomized, Controlled, Double-Blind Clinical Trial to Evaluate the Immunogenicity and Safety of the Co-administration of Live Attenuated Dengue and Chikungunya Vaccines Compared to Separate Administration.
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To ensure blinding of both participants and the study team performing safety assessments, vaccine preparation will be conducted by unblinded team members in a separate room, following the four-eyes principle (two individuals supervising the process). The syringes for different vaccination regimens will be pre-masked before being delivered to the study sites, ensuring the blinding process is maintained.
| DENGUE: Dengue 1,2,3,4 (attenuated) vaccine | Biological | DENGUE: Dose 10^2.5-4.1 PFU per virus (1,2,3,4) Route: Subcutaneous |
|
| Chikungunya (CHIKV) live attenuated vaccine (VLA1555) | Biological | CHIKUNGUNYA: Dose >= 3.0 log TCID50 per 0.5 mL Route: Intramuscular |
|
| Immunogenicity Secondary 2. | Assess the antibody response of co-administered Dengue and Chikungunya vaccines compared to Dengue and Chikungunya vaccines administered separately, in adults aged 18 to 59 years without prior exposure to either arbovirus, comparing the Geometric Mean Titer and the GMT ratio, for each dengue serotype and chikungunya, across all intervention groups. | 180 days post-immunization. |
| Safety Secondary 1. | Describe and compare the safety profile, by listing the Adverse Events of the co-administered Dengue and Chikungunya vaccines and Dengue and Chikungunya vaccines administered separately, reported in adults aged 18 to 59 years without prior exposure to either arbovirus. | up to 21 days post-immunization. |
| Safety Secondary 2. | Describe and compare the safety profile by listing Adverse Events of the co-administered Dengue and Chikungunya vaccines and Dengue and Chikungunya vaccines administered separately, in adults aged 18 to 59 years without prior exposure to either arbovirus. | 180 days post-immunization |
| Safety Secondary 3. | Describe post-vaccination viremia cases (manifestations). | Days 1, 6, 9, 16, and 22. |
| Toledo |
| Paraná |
| 85902-010 |
| Brazil |
|
| Hospital São Vicente de Paulo | Passo Fundo | Rio Grande do Sul | 99010-080 | Brazil |
|
| Hospital Escola da Universidade Federal de Pelotas | Pelotas | Rio Grande do Sul | 96040-010 | Brazil |
|
| Reumacenter | Porto Alegre | Rio Grande do Sul | 90480-000 | Brazil |
|
| UBEA - União Brasileira de Educação e Assistência Hospital São Lucas da PUCRS | Porto Alegre | Rio Grande do Sul | 90610-000 | Brazil |
|
| Instituto de Pesquisa em AIDS do Estado do Rio Grande do Sul - IPARGS | Porto Alegre | Rio Grande do Sul | 91350-180 | Brazil |
|
| 37321235 | Result | Schneider 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. |
| 39116904 | Result | 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. |
| 38294972 | Result | 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. |
| 32220283 | Result | Kallas 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. |
| 39255380 | Result | Chen LH, Fritzer A, Hochreiter R, Dubischar K, Meyer S. From bench to clinic: the development of VLA1553/IXCHIQ, a live-attenuated chikungunya vaccine. J Travel Med. 2024 Oct 19;31(7):taae123. doi: 10.1093/jtm/taae123. |
| ID | Term |
|---|---|
| D003715 | Dengue |
| D065632 | Chikungunya Fever |
| ID | Term |
|---|---|
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
| D007239 | Infections |
| D001102 | Arbovirus Infections |
| D014777 | Virus Diseases |
| D018177 | Flavivirus Infections |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006482 | Hemorrhagic Fevers, Viral |
| D018354 | Alphavirus Infections |
| D014036 | Togaviridae Infections |
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| ID | Term |
|---|---|
| D014613 | Vaccines, Attenuated |
| D014612 | Vaccines |
| ID | Term |
|---|---|
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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