A Phase 4 interventional study of Dengue 1,2,3,4 (attenuated) vaccine in Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA) and Systemic Lupus Erythematosus (SLE), sponsored by University of Sao Paulo General Hospital. Recruiting at 2 sites in Brazil. Open to participants aged 12 Years to 59 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-20.
Sponsored by University of Sao Paulo General Hospital · Phase 4, Interventional, and Prevention
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:
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.
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.
3,332 studies on the registry are indexed under Arthritis, Rheumatoid; 443 are open to participants now.
This study's planned enrollment of 477 is above the median of 96 across 2,220 interventional studies indexed under Arthritis, Rheumatoid.
Browse Arthritis, Rheumatoid studies →University of Sao Paulo General Hospital is the lead sponsor of 611 studies on the registry; 98 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with ARDs will receive 0.5 mL subcutaneous dose of Butantan-DV
Biological: Dengue 1,2,3,4 (attenuated) vaccine
Healthy subjects will receive 0.5 mL subcutaneous dose of Butantan-DV
Biological: Dengue 1,2,3,4 (attenuated) vaccine
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).
Also known as: Butantan-DV, TetraVax-DV-TV003
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.
Time frame: 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.
Time frame: Baseline through Day 42.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: Day 1
Plan to share: No
Started Mar 2026 (actual). Primary completion is estimated for Dec 2027, 21 months after the start.
Of 79 non-industry phase 4 interventional studies under Arthritis, Rheumatoid, half reached primary completion within 49 months of starting (the median), counting those still running; a quarter within 30 and three quarters within 92. This study's planned 21 months is below that.
Counting every sponsor, half of 104 studies reached it within 42 months; a quarter within 25 and three quarters within 74.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of Sao Paulo General Hospital →