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

NCT07087912 | Recruiting Phase 4 DMC

• 1 other identifier: 89470625.3.0000.0068
• Study Type: interventional
• Target: 477
• Locations: 1 country
• Sites: 2

Brief 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 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.

Conditions

Systemic Sclerosis (SSc); Idiopathic Inflammatory Myopathies (IIMs); Axial Spondyloarthritis; Psoriatic Arthritis (PsA); Granulomatosis With Polyangiitis; Microscopic Polyangiitis; Antiphospholipid Syndrome; Takayasu Arteritis; Juvenile Idiopathic Arthritis (JIA); Rheumatoid Arthritis (RA); Systemic Lupus Erythematosus (SLE); Juvenile Systemic Lupus Erythematosus

Keywords

Tetravalent Vaccine; Butantan-Dengue Vaccine; Autoimmune Rheumatic Diseases; Rheumatology; Pediatric Rheumatology; Infectious Disease Prevention; Vaccine

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline through Day 42.

Secondary Outcomes (11)

• Disease Activity Flares After Vaccination

  Day 1 to Day 42

• Frequency of Serious Adverse Events (SAEs)

  Day 1 through Day 400

• Frequency of Adverse Events of Special Interest (AESIs)

  Day 1 through Day 400

• Intensity of Viremia Post-Vaccination

  Days 1, 7, 14, 28, 42, and 68 (if viremia is detected)

• Duration of Viremia Post-Vaccination

  Days 1, 7, 14, 28, 42, and 68 (if viremia is detected)

Study Arms (2)

ARDs

EXPERIMENTAL

Patients with ARDs will receive 0.5 mL subcutaneous dose of Butantan-DV

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

Control

ACTIVE COMPARATOR

Healthy subjects will receive 0.5 mL subcutaneous dose of Butantan-DV

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

Interventions

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

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

ARDs; Control

Eligibility Criteria

• Age: 12 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead
• Butantan Institute: collaborator

Study Sites (2)

Hospital das Clínicas da Faculdade de Medicina da USP

São Paulo, São Paulo, 01246-903, Brazil

RECRUITING

Rheumatology Division, Faculdade de Medicina da USP

São Paulo, São Paulo, Brazil

RECRUITING

Related Publications (4)

• 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.

  PMID: 31589551 BACKGROUND

• Fernandez-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.

  PMID: 27537179 BACKGROUND

• Biswal 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.

  PMID: 31693803 BACKGROUND

• 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.

  PMID: 38294972 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis, Juvenile; Lupus Erythematosus, Systemic; Scleroderma, Systemic; Myositis; Axial Spondyloarthritis; Arthritis, Psoriatic; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Antiphospholipid Syndrome; Takayasu Arteritis

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Ankylosis; Psoriasis; Skin Diseases, Papulosquamous; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Aortic Arch Syndromes; Aortic Diseases; Arteritis

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Central Study Contacts

Clovis A Silva, Full Professor

CONTACT

+55 11 2661-8806; clovis.silva@hc.fm.usp.br

Eloisa SDO Bonfa, Full Professor

CONTACT

+55 11 3061-7490; reumatologia.fmusp@hc.fm.usp.br

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2025
• First Posted: July 28, 2025
• Study Start: March 16, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (2)