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)

Study Overview
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Brief Summary
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The purpose of this study is 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 is 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.

Official Title
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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

Conditions
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Dengue

Intervention / Treatment
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* Biological: V181
* Biological: Butantan-DV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male participants are eligible to participate if they agree to the following for at least 90 days after administration of study intervention: Abstain from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause). A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is NOT women of child-bearing potential (WOCBP); or is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or is 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. Have a negative highly sensitive pregnancy test (urine or serum, as required by local regulations) before administration of study intervention Is dengue seronegative based on a pre-vaccination point of care (POC) dengue test. Exclusion Criteria: Has a known history of dengue or Zika natural infection. Has an acute febrile illness (axillary temperature ≥37.8°C) occurring within 72 hours prior to receipt of study vaccine. Has 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. Has a serious or progressive disease, including but not limited to cancer, uncontrolled diabetes, severe cardiac, renal or hepatic insufficiency, systemic autoimmune or neurologic disorder. Has 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. Has 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 Has 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. Has received a licensed non-live vaccine within 14 days before receipt of study vaccine or is scheduled to receive any licensed non-live vaccine within 28 days following receipt of study vaccine. Exception: Inactivated influenza vaccine may be administered, but must be given at least 7 days before receipt of study vaccine or at least 28 days after receipt of study vaccine. Has received a licensed live vaccine within 28 days prior to receipt of study vaccine or is scheduled to receive any live vaccine within 28 days following receipt of study vaccine. Has 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 has not completed treatment at least 30 days before study entry or is expected to receive systemic corticosteroids at aforementioned dose and duration within 28 days following receipt of study vaccine. (Note: topical and inhaled/nebulized steroids are permitted.) Has received systemic corticosteroids exceeding physiologic replacement doses (approximately 5 mg/day prednisone equivalent) within 14 days before vaccination. Has 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. Has 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. Has planned donation of blood, eggs, or sperm at any time from signing the informed consent through 90 days post-vaccination.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V181<br>Participants will receive a single 0.5 mL subcutaneous (SC) injection of V181 on Day 1. | Biological: V181<br>* 0.5 mL SC dose of V181<br>|
| Experimental: Butantan-DV<br>Participants will receive a single 0.5 mL SC injection of Butantan-DV on Day 1. | Biological: Butantan-DV<br>* 0.5 mL SC dose of Butantan-DV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dengue virus-neutralizing antibody titers as measured by virus reduction neutralization test (VRNT) | Dengue virus-neutralizing antibody geometric mean titers (GMTs) for each of the 4 dengue serotypes (DENV1, DENV2, DENV3, and DENV4) as assessed by VRNT will be reported. | Day 28 post-vaccination | 
| Percentage of participants who seroconvert, as measured by VRNT | Seroconversion rates for each of the 4 dengue serotypes (DENV1, DENV2, DENV3 and DENV4) as assessed by VRNT will be reported. | Day 28 post-vaccination | 
| Percentage of participants who experience vaccine-related serious adverse events (SAEs) | The safety and tolerability of V181 and Butantan-DV with respect to the percentage of participants experiencing vaccine-related serious adverse events (SAEs) will be reported. | 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) | The safety and tolerability of V181 and Butantan-DV with respect to the percentage of participants experiencing solicited injection-site AEs, including injection site pain, erythema and swelling will be reported. | Up to 5 days post-vaccination | 
| Percentage of participants who experience solicited systemic AEs | The safety and tolerability of V181 and Butantan-DV with respect to the percentage of participants experiencing solicited systemic AEs, including rash, headache, fatigue (tiredness), myalgia (muscle pain) and arthralgia (joint pain) will be reported | Up to 28 days post-vaccination |