Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases

Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age12-59
SponsorUniversity of Sao Paulo General Hospital

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

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

    Biological/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).

Treatment groups

477 Participants
are divided into 2 treatment groups
Group A: ARDsExperimental treatment 1 intervention
Group B: ControlActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

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
2

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.

Secondary outcomes

1

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
2

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
3

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
4

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)

Other outcomes

Sponsors and contacts

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