Clinical Bridging Study Between V181 (Dengue Quadrivalent Vaccine rDENVΔ30 [Live, Attenuated]) to Butantan Dengue Vaccine (Butantan - DV) in Healthy Adults 18 to 50 Years of Age in Brazil (V181 - 002)

A Phase 2, Randomized, Double-Blind, Multicenter, Safety and Immunogenicity Clinical Bridging Study to Compare V181 (Dengue Quadrivalent Vaccine rDENVΔ30 [Live, Attenuated]) to Butantan Dengue Vaccine (Butantan - DV) in Healthy Adults 18 to 50 Years of Age in Brazil

The purpose of this study was to demonstrate that V181 is safe and well tolerated and elicits an immune response that is non-inferior to that of Butantan - DV at Day 28 post-vaccination in adults 18 to 50 years of age in Brazil. The primary hypothesis was that V181 is non-inferior to Butantan - DV for each of the 4 dengue serotypes based on geometric mean titers (GMTs) and seroconversion rates at Day 28 post-vaccination.

Study Overview

• Status: Completed
• Conditions: Dengue
• Intervention / Treatment: Biological: V181; Biological: Butantan - DV

• Study Type: Interventional
• Enrollment (Actual): 1364
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Bento Gonçalves, Rio Grande do Sul, Brazil, 95700084
      • Hospital Tacchini (Site 0006)
    • Caxias do Sul, Rio Grande do Sul, Brazil, 95070560
      • Fundação Universidade de Caxias do Sul (FUCS) - Instituto de Pesquisas em Saúde (IPS) (Site 0017)
    • Ijuí, Rio Grande do Sul, Brazil, 98700-000
      • ONCOSITE - Centro de Pesquisa Clinica em Oncologia (Site 0005)
    • Passo Fundo, Rio Grande do Sul, Brazil, 99010-080
      • Hospital São Vicente de Paulo-Education and Research Management (Site 0007)
    • Passo Fundo, Rio Grande do Sul, Brazil, 99010-120
      • Instituto Méderi de Pesquisa e Saúde (0020)
    • Pelotas, Rio Grande do Sul, Brazil, 96020-360
      • Hospital Escola da Universidade Federal de Pelotas (Site 0009)
    • Porto Alegre, Rio Grande do Sul, Brazil, 90020-090
      • Irmandade da Santa Casa de Misericórdia de Porto Alegre-Centro de Pesquisa em Infectologia (Site # 003)
    • Porto Alegre, Rio Grande do Sul, Brazil, 90430-001
      • Núcleo de Pesquisa Clínica do Rio Grande do Sul (Site 0011)
    • Porto Alegre, Rio Grande do Sul, Brazil, 90480-000
      • LMK Serviços Médicos S/S-Reumacenter (Site 0004)
    • Porto Alegre, Rio Grande do Sul, Brazil, 90560-030
      • Hospital Moinhos de Vento - Centro de Pesquisa Clínica (Site0021)
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital São Lucas da PUCRS-Centro de Pesquisa Clínica HSL-PUCRS (Site 0015)
    • Santa Maria, Rio Grande do Sul, Brazil, 97105-900
      • Universidade Federal de Santa Maria (UFSM) - Hospital Univer-Unidade de Pesquisa Clínica-UPC (Site 0001)
  • Santa Catarina
    • Chapecó, Santa Catarina, Brazil, 89812-211
      • Clínica Supera (Site 0019)
    • Passo Fundo, Santa Catarina, Brazil, 88811508
      • Criciuma (Site 0008)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male participants were eligible to participate if they agreed to the following for at least 90 days after administration of study intervention:

  • Abstained from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agreed to remain abstinent; or agreed to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause).

• A female participant was eligible to participate if she was not pregnant or breastfeeding, and at least one of the following conditions applies:

  • was NOT a woman of child-bearing potential (WOCBP); or
  • was a WOCBP and using a contraceptive a highly effective method (with a failure rate of <1% per year), or
  • was abstinent from heterosexual intercourse as her preferred and usual lifestyle (abstinent on a long term and persistent basis), for at least 90 days after administration of study intervention.
  • Had a negative highly sensitive pregnancy test (urine or serum, as required by local regulations) before administration of study intervention
• Were dengue seronegative based on a pre-vaccination point of care (POC) dengue test.

Exclusion Criteria:

• Had a known history of dengue or Zika natural infection.
• Had an acute febrile illness (axillary temperature ≥37.8°C) occurring within 72 hours prior to receipt of study vaccine.
• Had a known hypersensitivity or history of severe allergic reaction (eg, swelling of the mouth and throat, difficulty breathing, hypotension or shock) to any component of the dengue vaccine, that required medical intervention.
• Had a serious or progressive disease, including but not limited to cancer, uncontrolled diabetes, severe cardiac, renal or hepatic insufficiency, systemic autoimmune or neurologic disorder.
• Had known or suspected impairment of immunological function, including but not limited to congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, hematologic malignancy, or treatment for autoimmune diseases.
• Had a condition in which repeated venipuncture or injections pose more than minimal risk, such as hemophilia, thrombocytopenia, other severe coagulation disorders, or significantly impaired venous access
• Had received a dose of any dengue vaccine (investigational or approved) prior to study entry or plans to receive any dengue vaccine (investigational or approved) for trial duration.
• Had received a licensed non-live vaccine within 14 days before receipt of study vaccine or was scheduled to receive any licensed non-live vaccine within 28 days following receipt of study vaccine. Exception: Inactivated influenza vaccine might be administered, but given at least 7 days before receipt of study vaccine or at least 28 days after receipt of study vaccine.
• Had received a licensed live vaccine within 28 days prior to receipt of study vaccine or was scheduled to receive any live vaccine within 28 days following receipt of study vaccine.
• Had received systemic corticosteroids (equivalent of ≥2 mg/kg/day of prednisone or ≥20 mg/day for persons weighing >10 kg) for ≥14 consecutive days and had not completed treatment at least 30 days before study entry or was expected to receive systemic corticosteroids at aforementioned dose and duration within 28 days following receipt of study vaccine. (Note: topical and inhaled/nebulized steroids were permitted.)
• Had received systemic corticosteroids exceeding physiologic replacement doses (approximately 5 mg/day prednisone equivalent) within 14 days before vaccination.
• Had received immunosuppressive therapies, including chemotherapeutic agents used to treat cancer or other conditions, treatments associated with organ or bone marrow transplantation, or autoimmune disease, within 6 months prior to receipt of study vaccine, or plans to receive immunosuppressive therapies within 28 days following receipt of study vaccine.
• Had received a blood transfusion or blood products (including immunoglobulins) within 6 months prior to receipt of study vaccine or plans to receive a blood transfusion or blood products (including immunoglobulins) within 28 days following receipt of study vaccine.
• Had planned donation of blood, eggs, or sperm at any time from signing the informed consent through 90 days post-vaccination.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V181; Participants received a single 0.5 mL subcutaneous (SC) injection of V181.	Biological: V181; 0.5 mL SC dose of V181
Experimental: Butantan - DV; Participants received a single 0.5 mL SC injection of Butantan - DV.	Biological: Butantan - DV; 0.5 mL SC dose of Butantan - DV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dengue Virus (DENV)-Neutralizing Antibody Titers as Measured by Virus Reduction Neutralization Test (VRNT)	A dengue VRNT was conducted to assess neutralizing antibody geometric mean titers (GMTs) for each of the 4 dengue serotypes (DENV1, DENV2, DENV3, and DENV4) in specimens collected from participants on Day 28 post-vaccination	Day 28 post-vaccination
Percentage of Participants Who Seroconverted, as Measured by VRNT	A dengue VRNT was conducted to assess the percentage of participants who seroconverted for each of the 4 dengue serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) at Day 28 post-vaccination. Seroconversion was defined as achieving a serotype-specific VRNT titer ≥lower limit of quantification (LLOQ) at Day 28 post-vaccination in the analysis population.	Day 28 post-vaccination
Percentage of Participants With Vaccine-related Serious Adverse Events (SAEs)	An SAE is an AE that results in death, is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. Relatedness of an SAE to the study vaccine was determined by the investigator.	Up to 28 days post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experience Solicited Injection-site Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited injection-site AEs included erythema (redness), pain, and swelling.	Up to 5 days post-vaccination
Percentage of Participants Who Experience Solicited Systemic AEs	An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs include arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain), pyrexia (axillary temperature ≥37.8°C or 100°F), and rash.	Up to 28 days post-vaccination

Collaborators and Investigators

• Sponsor: Butantan Institute
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Actual): January 22, 2024
• Study Completion (Actual): December 12, 2024

Study Registration Dates

• First Submitted: January 24, 2023
• First Submitted That Met QC Criteria: January 24, 2023
• First Posted (Actual): February 2, 2023

Study Record Updates

• Last Update Posted (Estimated): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue
• Other Study ID Numbers: V181- 002; 25351.019896/2021- 84 (Other Identifier: Agência Nacional de Vigilância Sanitária (Brazilian Health Regulatory Agency) (ANVISA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes