Rheumatoid Arthritis (RA)Phase 4BTNDV-ARDNCT07087912
Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases
A Phase 4 study testing Dengue 1,2,3,4 (attenuated) vaccine in people with Rheumatoid Arthritis (RA) and Juvenile Idiopathic Arthritis (JIA), run by University of Sao Paulo General Hospital at 2 sites in Brazil.
Trial summary
The goal of this clinical trial is to evaluate whether the live attenuated tetravalent Butantan-Dengue vaccine (Butantan-DV) is safe and capable of inducing an immune response in patients aged 12 to 59 years with autoimmune rheumatic diseases (ARDs) who are clinically stable and under low-grade or no… Read more about this study
- Who is it for?
- Ages 12 to 59 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA), Systemic Lupus Erythematosus (SLE)
- What is being tested?
- Dengue 1,2,3,4 (attenuated) vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 477 participants
- Where
- 2 sitesBrazil
- Study dates
- 16 Mar 2026to 30 Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 59 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Age between 12 and 59 years
- Male or female
- Clinical diagnosis of an autoimmune rheumatic disease (ARD) based on internationally accepted criteria (e.g., rheumatoid arthritis, systemic lupus erythematosus, juvenile idiopathic arthritis, Sjögren's syndrome, vasculitis)
- Healthy control matched by age and sex
- ARD patients with clinically stable disease for at least 3 months
- ARD patients under low-grade immunosuppression or no immunosuppression
Show all 12Show fewer
- Acceptable immunosuppressive treatments include:
- Hydroxychloroquine Sulfasalazine Prednisone ≤ 20 mg/day Methotrexate ≤ 0.4 mg/kg/week (maximum 20 mg/week) Leflunomide 20 mg/day Azathioprine < 3 mg/kg/day Combination therapy with low-dose prednisone (≤ 7.5 mg/day), hydroxychloroquine, or sulfasalazine
- Healthy controls with no history of autoimmune or chronic infectious diseases
- Healthy controls not taking immunosuppressive medications Willing and able to comply with study procedures and follow-up
- Female participants of reproductive potential with negative pregnancy test at baseline
- Female participants of reproductive potential agreeing to use effective contraception for at least 90 days after vaccination
Who cannot join
- Prior receipt of any dengue vaccine
- Receipt of a live attenuated vaccine within 4 weeks prior to enrollment
- Receipt of an inactivated vaccine within 2 weeks prior to enrollment
- Known allergy to any component of the vaccine
- Febrile illness (≥ 37.8°C) within 72 hours prior to vaccination
- History of immunodeficiency syndromes
Show all 17Show fewer
- History of asplenia
- History of cancer
- History of HIV infection
- History of primary immunodeficiencies
- Immunosuppression due to organ transplant
- Chronic uncontrolled comorbidities (e.g., heart failure, renal failure, hepatic insufficiency, diabetes mellitus)
- Hospitalization or acute illness at screening
- Receipt of blood transfusion within 3 months prior to enrollment
- Current pregnancy or breastfeeding
- Intention to become pregnant within 90 days post-vaccination
- Participation in another clinical trial within 30 days prior to enrollment
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil2 sites, 2 recruiting
- Recruiting
Hospital das Clínicas da Faculdade de Medicina da USP
São Paulo, São Paulo, 01246-903
- Recruiting
Rheumatology Division, Faculdade de Medicina da USP
São Paulo, São Paulo
Clovis A Silva, Full professor, +55 11 2661-8806, clovis.silva@hc.fm.usp.br
Eloisa SDO Bonfa, Full Professor, reumatologia.fmusp@hc.fm.usp.br
About this study
Official title: Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine (Butantan-DV) in Patients With Autoimmune Rheumatic Diseases Living in Dengue-Endemic Areas
The goal of this clinical trial is to evaluate whether the live attenuated tetravalent Butantan-Dengue vaccine (Butantan-DV) is safe and capable of inducing an immune response in patients aged 12 to 59 years with autoimmune rheumatic diseases (ARDs) who are clinically stable and under low-grade or no immunosuppression, as well as in healthy volunteers matched by sex and age.
The main questions it aims to answer are:
Read more
Does the vaccine induce adequate seroconversion in patients with ARDs compared to healthy controls? What is the frequency and intensity of common adverse events after vaccination in ARDs patients? Does physical activity levels and nutritional status influence vaccine-induced immune response in patients with ARDs?
Researchers will compare patients with ARDs to healthy controls to evaluate if the vaccine elicits similar immune responses and safety profiles.
All participants will:
- receive a single 0.5 mL dose of the Butantan-DV vaccine via subcutaneous injection;
- undergo blood sample collection before and after vaccination (baseline, Day 42, and Day 400) to assess antibody and cellular responses;
- attend follow-up visits on Days 7, 14, and 42 for safety monitoring and laboratory tests;
- report any symptoms or adverse events using a standardized diary for 42 days;
- be followed for up to one year for long-term safety and immunogenicity assessments.
- wear a device for 14 consecutive days to assess current and habitual physical activity levels.
- answer three non-consecutive 24-hour dietary recalls, including at least one weekend day to assess nutritional status.
- collect blood samples one-year after vaccination to access immunogenicity and cellular response.
Researcher will also perform subgroups analysis in:
A viremia subgroup (50 patients and 50 healthy controls) will provide additional samples on Days 1, 7, 14, 28, 42, and-if viremia is detected-Day 68, to evaluate post-vaccination viremia and its duration.
An immunogenicity subgroup (~20% of participants, n=96) will undergo cellular immune response testing via flow cytometry to evaluate T-cell responses.
Read the detailed description
Dengue is hyper-endemic in Brazil, with millions of probable cases and a growing burden of hospitalisation and death each year. Patients with autoimmune rheumatic diseases (ARDs) are especially vulnerable because their underlying immune dysregulation and the use of immunosuppressive agents increase the risk of severe infection and poor outcomes. Current rheumatology guidelines recommend vaccination, yet live-attenuated products are traditionally avoided unless immunosuppression is minimal, leaving an important evidence gap for this population.
The Butantan-DV vaccine is a single-dose, tetravalent, live-attenuated formulation derived from all four dengue serotypes. Phase II-III data in the general population have demonstrated an overall efficacy of ~80 % and an acceptable safety profile, with clear operational advantages over other licensed vaccines (broader age indication and single-dose schedule). However, its immunogenicity and safety have not been prospectively examined in ARD patients under low-grade or no immunosuppression-precisely the subgroup for whom live vaccines may be permissible but still pose theoretical risks.
This open-label, Phase IIIb, prospective study will enrol 318 clinically stable ARD patients (ages 12-59 years) on low-grade or no immunosuppression and 159 age- and sex-matched healthy controls living in dengue-endemic areas. All participants receive a single 0.5 mL subcutaneous dose of Butantan-DV on Day 1. Core follow-up visits occur on Days 7, 14 and 42 for clinical assessment, laboratory safety panels and adverse-event diary review; long-term surveillance continues to Day 400 to characterise antibody persistence and late safety signals.
Two exploratory components will be evaluated:
Viremia substudy: 50 patients and 50 controls undergo additional sampling on Days 1, 7, 14, 28, 42 (and Day 68 if viraemic) to quantify the incidence, magnitude and duration of post-vaccination viremia by multiplex RT-PCR.
Cellular-immunity substudy: ~20 % of participants provide peripheral blood mononuclear cells at baseline, Day 42 and Day 400 for intracellular cytokine staining to define CD8+ T-cell responses against pooled dengue peptides, filling a key knowledge gap on cell-mediated protection in immunocompromised hosts.
Safety oversight is reinforced by a predefined toxicity-grading schema, 24-hour study hotline, systematic capture of solicited/unsolicited adverse events through Day 42, and independent Data and Safety Monitoring Board review at six-month intervals or ad-hoc for any serious events.
Disease-activity flares will be tracked with validated indices tailored to each ARD diagnosis (e.g., DAS-28, SLEDAI-2K, ASDAS) on Days 1 and 42 to distinguish vaccine reactogenicity from underlying disease exacerbation.
Physical activity will be assessed using validated questionnaires at D1 and objective accelerometry (D1-D14), while dietary intake will be evaluated through repeated 24-hour dietary recalls and food quality classification starting at D1.
The primary scientific contribution is to establish whether seroconversion rates (PRNT50) in low-grade immunosuppressed ARD patients are non-inferior to healthy controls at Day 42, while rigorously quantifying common and serious adverse events. Secondary analyses explore viremia kinetics, T-cell immunity, antibody durability to one year, and host- or treatment-related modifiers of vaccine response.
By integrating comprehensive immunologic endpoints with robust safety monitoring, this trial will provide the first high-quality evidence to inform dengue vaccination policy for children, adolescents and adults living with ARDs in endemic regions-potentially broadening individual protection and supporting public-health efforts to mitigate dengue's impact in Brazil and similar settings.
- Conditions
- Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA), Systemic Lupus Erythematosus (SLE), Juvenile Systemic Lupus Erythematosus, Systemic Sclerosis (SSc), Idiopathic Inflammatory Myopathies (IIMs)
- Being tested
- Dengue 1,2,3,4 (attenuated) vaccine
- Keywords
- Tetravalent Vaccine, Butantan-Dengue Vaccine, Autoimmune Rheumatic Diseases, Rheumatology, Pediatric Rheumatology, Infectious Disease Prevention, Vaccine
- Medical subject headings
- Arthritis, Rheumatoid, Arthritis, Juvenile, Lupus Erythematosus, Systemic, Scleroderma, Systemic, Myositis, Axial Spondyloarthritis, Arthritis, Psoriatic, Granulomatosis with Polyangiitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dengue 1,2,3,4 (attenuated) vaccineBiological
Also called Butantan-DV, TetraVax-DV-TV003
A single 0.5 mL dose of the live attenuated tetravalent dengue vaccine (Butantan-DV), administered subcutaneously on Day 1. The vaccine contains attenuated viral strains for DENV-1, DENV-3, DENV-4, and a chimeric DENV-2 component. It is manufactured and formulated by the Instituto Butantan (São Paulo, Brazil).
| Study group | Role | What they receive |
|---|---|---|
| ARDs | Experimental | Patients with ARDs will receive 0.5 mL subcutaneous dose of Butantan-DV Receives: Biological: Dengue 1,2,3,4 (attenuated) vaccine |
| Control | Active comparator | Healthy subjects will receive 0.5 mL subcutaneous dose of Butantan-DV Receives: Biological: Dengue 1,2,3,4 (attenuated) vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seroconversion Rate After Vaccination
Proportion of participants who achieve seroconversion (defined by PRNT50 neutralizing antibody titers) for any dengue serotype at Day 42 following a single dose of the Butantan-DV vaccine. Comparisons will be made between patients with autoimmune rheumatic diseases (ARDs) and healthy controls.
Measured: From enrollment to day 42 after vaccination
Frequency and Intensity of Common Adverse Events
Frequency and intensity of solicited local and systemic adverse events (e.g., pain at injection site, fever, headache, fatigue) with frequency up to 1/100, up to Day 42 post-vaccination, classified according to severity grading. Comparisons will be made between ARD patients and healthy controls.
Measured: Baseline through Day 42.
Secondary outcomes (11)
Disease Activity Flares After Vaccination
Number of patients with autoimmune rheumatic diseases (ARDs) who experience a flare or increase in disease activity, as defined by validated disease-specific indices (e.g., DAS28, SLEDAI-2K, ASDAS), between Day 1 and Day 42.
Measured: Day 1 to Day 42
Frequency of Serious Adverse Events (SAEs)
To evaluate safety of the vaccine. Frequency of serious adverse events (hospitalizations, death, confirmed dengue with warning signs or severe dengue) occurring at any time during the study period in ARD patients compared to healthy controls.
Measured: Day 1 through Day 400
Frequency of Adverse Events of Special Interest (AESIs)
Frequency of AESIs, including immune-mediated disorders, dengue infection post-vaccination, and other medically significant events, throughout the study duration.
Measured: Day 1 through Day 400
Intensity of Viremia Post-Vaccination
Quantification and comparison of dengue viremia levels among ARD patients and healthy controls in a viremia substudy group, using RT-PCR at specified time points.
Measured: Days 1, 7, 14, 28, 42, and 68 (if viremia is detected)
Duration of Viremia Post-Vaccination
Quantification, comparison and duration of dengue viremia levels among ARD patients and healthy controls in a viremia substudy group, using RT-PCR at specified time points.
Measured: Days 1, 7, 14, 28, 42, and 68 (if viremia is detected)
Frequency of Grade 3 or 4 Adverse Events
Comparison of the frequency of grade 3 or 4 adverse events (as defined by severity scales) between ARD patients and healthy controls.
Measured: Day 1 to Day 42
Geometric Mean Titers Against Dengue Serotypes
Comparison of the geometric mean antibody titers (GMTs) against DENV-1, DENV-2, DENV-3, and DENV-4 between ARD patients and healthy controls, as measured by PRNT50.
Measured: Day 1 and Day 42
Factors Associated With Vaccine Immunogenicity
Identification of clinical and demographic variables associated with vaccine-induced antibody response in ARD patients, including prior dengue exposure, disease activity, and treatment regimen.
Measured: Day 1 and Day 42
Persistence of Antibody Response
Evaluation of antibody titers against all four dengue serotypes one year post-vaccination in ARD patients and healthy controls.
Measured: Day 400
Influence of Physical Activity Levels on Vaccine-Induced Humoral Immune Response
To assess the association between accelerometry-derived metrics (moderate-to-vigorous activity time, sedentary behavior, vector magnitude) and humoral immune response
Measured: Day 1 to 14
Influence of dietary intake on Vaccine-Induced Humoral Immune Response
Dietary intake will be assessed using three non-consecutive 24-hour recalls, including one weekend day, analyzed via Dietbox software. Energy and macronutrient intake will be calculated, and food quality assessed based on the NOVA classification by level of processing.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2025
- Study start16 Mar 2026
- Primary completion30 Dec 2027 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid Arthritis (RA)Studies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 477 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Butantan Institute
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07087912
- Sponsor's protocol ID
- 89470625.3.0000.0068
- Acronym
- BTNDV-ARD
- Status last verified
- Apr 2026
- First submitted
- 30 Jun 2025
- Last updated
- 20 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Thomas SJ, Yoon IK. A review of Dengvaxia(R): development to deployment. Hum Vaccin Immunother. 2019;15(10):2295-2314. doi: 10.1080/21645515.2019.1658503. Epub 2019 Oct 7.
PubMed 31589551Fernandez-Martinez S, Cortes X, Borras-Blasco J, Gracia-Perez A, Castera ME. Effectiveness of a systematic vaccination program in patients with autoimmune inflammatory disease treated with anti-TNF alpha drugs. Expert Opin Biol Ther. 2016 Nov;16(11):1317-1322. doi: 10.1080/14712598.2016.1218844. Epub 2016 Aug 18.
PubMed 27537179Biswal S, Reynales H, Saez-Llorens X, Lopez P, Borja-Tabora C, Kosalaraksa P, Sirivichayakul C, Watanaveeradej V, Rivera L, Espinoza F, Fernando L, Dietze R, Luz K, Venancio da Cunha R, Jimeno J, Lopez-Medina E, Borkowski A, Brose M, Rauscher M, LeFevre I, Bizjajeva S, Bravo L, Wallace D; TIDES Study Group. Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents. N Engl J Med. 2019 Nov 21;381(21):2009-2019. doi: 10.1056/NEJMoa1903869. Epub 2019 Nov 6.
PubMed 31693803Kallas 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.
PubMed 38294972
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine (Butantan-DV) in Patients With Autoimmune Rheumatic Diseases Living in Dengue-Endemic Areas
- ClinicalTrials.gov ID
- NCT07087912
- Acronym / sponsor ID
- BTNDV-ARD / 89470625.3.0000.0068
- Conditions
- Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA), Systemic Lupus Erythematosus (SLE), Juvenile Systemic Lupus Erythematosus, Systemic Sclerosis (SSc), Idiopathic Inflammatory Myopathies (IIMs)
- Keywords
- Tetravalent Vaccine, Butantan-Dengue Vaccine, Autoimmune Rheumatic Diseases, Rheumatology, Pediatric Rheumatology, Infectious Disease Prevention, Vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 477 participants (estimated)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Collaborators
- Butantan Institute
- Study start
- 16 Mar 2026 (actual)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 28 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate whether the live attenuated tetravalent Butantan-Dengue vaccine (Butantan-DV) is safe and capable of inducing an immune response in patients aged 12 to 59 years with autoimmune rheumatic diseases (ARDs) who are clinically stable and under low-grade or no immunosuppression, as well as in healthy volunteers matched by sex and age.
The main questions it aims to answer are:
Does the vaccine induce adequate seroconversion in patients with ARDs compared to healthy controls? What is the frequency and intensity of common adverse events after vaccination in ARDs patients? Does physical activity levels and nutritional status influence vaccine-induced immune response in patients with ARDs?
Researchers will compare patients with ARDs to healthy controls to evaluate if the vaccine elicits similar immune responses and safety profiles.
All participants will:
- receive a single 0.5 mL dose of the Butantan-DV vaccine via subcutaneous injection;
- undergo blood sample collection before and after vaccination (baseline, Day 42, and Day 400) to assess antibody and cellular responses;
- attend follow-up visits on Days 7, 14, and 42 for safety monitoring and laboratory tests;
- report any symptoms or adverse events using a standardized diary for 42 days;
- be followed for up to one year for long-term safety and immunogenicity assessments.
- wear a device for 14 consecutive days to assess current and habitual physical activity levels.
- answer three non-consecutive 24-hour dietary recalls, including at least one weekend day to assess nutritional status.
- collect blood samples one-year after vaccination to access immunogenicity and cellular response.
Researcher will also perform subgroups analysis in:
A viremia subgroup (50 patients and 50 healthy controls) will provide additional samples on Days 1, 7, 14, 28, 42, and-if viremia is detected-Day 68, to evaluate post-vaccination viremia and its duration.
An immunogenicity subgroup (~20% of participants, n=96) will undergo cellular immune response testing via flow cytometry to evaluate T-cell responses.
Detailed description
Dengue is hyper-endemic in Brazil, with millions of probable cases and a growing burden of hospitalisation and death each year. Patients with autoimmune rheumatic diseases (ARDs) are especially vulnerable because their underlying immune dysregulation and the use of immunosuppressive agents increase the risk of severe infection and poor outcomes. Current rheumatology guidelines recommend vaccination, yet live-attenuated products are traditionally avoided unless immunosuppression is minimal, leaving an important evidence gap for this population.
The Butantan-DV vaccine is a single-dose, tetravalent, live-attenuated formulation derived from all four dengue serotypes. Phase II-III data in the general population have demonstrated an overall efficacy of ~80 % and an acceptable safety profile, with clear operational advantages over other licensed vaccines (broader age indication and single-dose schedule). However, its immunogenicity and safety have not been prospectively examined in ARD patients under low-grade or no immunosuppression-precisely the subgroup for whom live vaccines may be permissible but still pose theoretical risks.
This open-label, Phase IIIb, prospective study will enrol 318 clinically stable ARD patients (ages 12-59 years) on low-grade or no immunosuppression and 159 age- and sex-matched healthy controls living in dengue-endemic areas. All participants receive a single 0.5 mL subcutaneous dose of Butantan-DV on Day 1. Core follow-up visits occur on Days 7, 14 and 42 for clinical assessment, laboratory safety panels and adverse-event diary review; long-term surveillance continues to Day 400 to characterise antibody persistence and late safety signals.
Two exploratory components will be evaluated:
Viremia substudy: 50 patients and 50 controls undergo additional sampling on Days 1, 7, 14, 28, 42 (and Day 68 if viraemic) to quantify the incidence, magnitude and duration of post-vaccination viremia by multiplex RT-PCR.
Cellular-immunity substudy: ~20 % of participants provide peripheral blood mononuclear cells at baseline, Day 42 and Day 400 for intracellular cytokine staining to define CD8+ T-cell responses against pooled dengue peptides, filling a key knowledge gap on cell-mediated protection in immunocompromised hosts.
Safety oversight is reinforced by a predefined toxicity-grading schema, 24-hour study hotline, systematic capture of solicited/unsolicited adverse events through Day 42, and independent Data and Safety Monitoring Board review at six-month intervals or ad-hoc for any serious events.
Disease-activity flares will be tracked with validated indices tailored to each ARD diagnosis (e.g., DAS-28, SLEDAI-2K, ASDAS) on Days 1 and 42 to distinguish vaccine reactogenicity from underlying disease exacerbation.
Physical activity will be assessed using validated questionnaires at D1 and objective accelerometry (D1-D14), while dietary intake will be evaluated through repeated 24-hour dietary recalls and food quality classification starting at D1.
The primary scientific contribution is to establish whether seroconversion rates (PRNT50) in low-grade immunosuppressed ARD patients are non-inferior to healthy controls at Day 42, while rigorously quantifying common and serious adverse events. Secondary analyses explore viremia kinetics, T-cell immunity, antibody durability to one year, and host- or treatment-related modifiers of vaccine response.
By integrating comprehensive immunologic endpoints with robust safety monitoring, this trial will provide the first high-quality evidence to inform dengue vaccination policy for children, adolescents and adults living with ARDs in endemic regions-potentially broadening individual protection and supporting public-health efforts to mitigate dengue's impact in Brazil and similar settings.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARDs | Experimental | Biological: Dengue 1,2,3,4 (attenuated) vaccinePatients with ARDs will receive 0.5 mL subcutaneous dose of Butantan-DV |
| Control | Active comparator | Biological: Dengue 1,2,3,4 (attenuated) vaccineHealthy subjects will receive 0.5 mL subcutaneous dose of Butantan-DV |
Who may qualify
- Ages
- 12 to 59 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Age between 12 and 59 years
- Male or female
- Clinical diagnosis of an autoimmune rheumatic disease (ARD) based on internationally accepted criteria (e.g., rheumatoid arthritis, systemic lupus erythematosus, juvenile idiopathic arthritis, Sjögren's syndrome, vasculitis)
- Healthy control matched by age and sex
- ARD patients with clinically stable disease for at least 3 months
Key exclusion criteria (17 listed)
- Prior receipt of any dengue vaccine
- Receipt of a live attenuated vaccine within 4 weeks prior to enrollment
- Receipt of an inactivated vaccine within 2 weeks prior to enrollment
- Known allergy to any component of the vaccine
- Febrile illness (≥ 37.8°C) within 72 hours prior to vaccination
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dengue 1,2,3,4 (attenuated) vaccineAlso: Butantan-DV, TetraVax-DV-TV003A single 0.5 mL dose of the live attenuated tetravalent dengue vaccine (Butantan-DV), administered subcutaneously on Day 1. The vaccine contains attenuated viral strains for DENV-1, DENV-3, DENV-4, and a chimeric DENV-2 component. It is manufactured and formulated by the Instituto Butantan (São Paulo, Brazil). | Biological | ARDs, Control |
Primary outcome
Seroconversion Rate After Vaccination
Time frame: From enrollment to day 42 after vaccination
Proportion of participants who achieve seroconversion (defined by PRNT50 neutralizing antibody titers) for any dengue serotype at Day 42 following a single dose of the Butantan-DV vaccine. Comparisons will be made between patients with autoimmune rheumatic diseases (ARDs) and healthy controls.
Frequency and Intensity of Common Adverse Events
Time frame: Baseline through Day 42.
Frequency and intensity of solicited local and systemic adverse events (e.g., pain at injection site, fever, headache, fatigue) with frequency up to 1/100, up to Day 42 post-vaccination, classified according to severity grading. Comparisons will be made between ARD patients and healthy controls.
11 secondary outcomes
Disease Activity Flares After Vaccination
Time frame: Day 1 to Day 42
Frequency of Serious Adverse Events (SAEs)
Time frame: Day 1 through Day 400
Frequency of Adverse Events of Special Interest (AESIs)
Time frame: Day 1 through Day 400
Intensity of Viremia Post-Vaccination
Time frame: Days 1, 7, 14, 28, 42, and 68 (if viremia is detected)
Duration of Viremia Post-Vaccination
Time frame: Days 1, 7, 14, 28, 42, and 68 (if viremia is detected)
Frequency of Grade 3 or 4 Adverse Events
Time frame: Day 1 to Day 42
Geometric Mean Titers Against Dengue Serotypes
Time frame: Day 1 and Day 42
Factors Associated With Vaccine Immunogenicity
Time frame: Day 1 and Day 42
Persistence of Antibody Response
Time frame: Day 400
Influence of Physical Activity Levels on Vaccine-Induced Humoral Immune Response
Time frame: Day 1 to 14
Influence of dietary intake on Vaccine-Induced Humoral Immune Response
Time frame: Day 1
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2026.
- Background: PubMed 31589551Thomas SJ, Yoon IK. A review of Dengvaxia(R): development to deployment. Hum Vaccin Immunother. 2019;15(10):2295-2314. doi: 10.1080/21645515.2019.1658503. Epub 2019 Oct 7.
- Background: PubMed 27537179Fernandez-Martinez S, Cortes X, Borras-Blasco J, Gracia-Perez A, Castera ME. Effectiveness of a systematic vaccination program in patients with autoimmune inflammatory disease treated with anti-TNF alpha drugs. Expert Opin Biol Ther. 2016 Nov;16(11):1317-1322. doi: 10.1080/14712598.2016.1218844. Epub 2016 Aug 18.
- Background: PubMed 31693803Biswal S, Reynales H, Saez-Llorens X, Lopez P, Borja-Tabora C, Kosalaraksa P, Sirivichayakul C, Watanaveeradej V, Rivera L, Espinoza F, Fernando L, Dietze R, Luz K, Venancio da Cunha R, Jimeno J, Lopez-Medina E, Borkowski A, Brose M, Rauscher M, LeFevre I, Bizjajeva S, Bravo L, Wallace D; TIDES Study Group. Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents. N Engl J Med. 2019 Nov 21;381(21):2009-2019. doi: 10.1056/NEJMoa1903869. Epub 2019 Nov 6.
- Background: PubMed 38294972Kallas 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dengue 1,2,3,4 (attenuated) vaccine in people with Rheumatoid Arthritis (RA) and Juvenile Idiopathic Arthritis (JIA), run by University of Sao Paulo General Hospital at 2 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clovis A Silva, Full Professor (+55 11 2661-8806, clovis.silva@hc.fm.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Seroconversion Rate After Vaccination (time frame: From enrollment to day 42 after vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07087912, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026.