Safety and Immunogenicity of Three V181 Dengue Vaccine Potencies in Adults (V181-003)

Study Overview
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Brief Summary
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The primary objective of this study is to compare the dengue virus-neutralizing antibody geometric mean titers (GMTs) for each of the 4 dengue serotypes (DENV1, DENV2, DENV3, and DENV4) at Day 28 post-vaccination for participants administered the V181 Low-Potency Level vaccine versus the V181 Mid-Potency Level vaccine. This study will also evaluate the safety and tolerability of 3 different V181 potency level vaccines. The primary hypothesis of the study is that the V181 Low-Potency Level vaccine is non-inferior to the V181 Mid-Potency Level vaccine for each of the 4 dengue serotypes based on GMTs at Day 28 post-vaccination.

Official Title
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A Phase 2, Randomized, Double-Blind, Multicenter Study to Evaluate the Safety and Immunogenicity of Three Different Potency Levels of V181 (Dengue Quadrivalent Vaccine rDENVΔ30 [Live, Attenuated]) in Healthy Adults

Conditions
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Dengue Disease, Dengue Virus

Intervention / Treatment
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* Biological: V181 High-Potency Level
* Biological: V181 Mid-Potency Level
* Biological: V181 Low-Potency Level
* Biological: Placebo


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; 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. (Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.) Exclusion Criteria: Has known history of dengue or zika natural infection. Has an acute febrile illness (temperature ≥38.0°C [≥100.4°F] oral or equivalent) occurring within 72 hours before receipt of study vaccine or placebo. Has a serious or progressive disease, including but not limited to cancer; uncontrolled diabetes; severe cardiac, renal, or hepatic insufficiency; or 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 for the participant, such as hemophilia, thrombocytopenia, other severe coagulation disorders, or significantly impaired venous access. Has a known hypersensitivity to any component of the study vaccine or placebo, or history of severe allergic reaction (eg, swelling of the mouth and throat, difficulty breathing, hypotension or shock) that required medical intervention. Has received a dose of any dengue vaccine (investigational or approved) before study entry, or plans to receive any dengue vaccine (investigational or approved) for the duration of the trial. Has received other licensed non-live vaccines within 14 days before receipt of study vaccine or placebo, or is scheduled to receive any licensed non-live vaccine within 28 days following receipt of study vaccine or placebo. Exception: Inactivated influenza vaccine may be administered but must be given at least 7 days before receipt of study vaccine or placebo, or at least 28 days after receipt of study vaccine or placebo. Has received a licensed live vaccine within 28 days before receipt of study vaccine or placebo, or is scheduled to receive any live vaccine within 28 days following receipt of study vaccine or placebo. Has received systemic corticosteroids (equivalent of ≥2 mg/kg/day of prednisone or ≥20 mg/d 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 or placebo. (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 before receipt of study vaccine or placebo, or plans to receive immunosuppressive therapies within 28 days following receipt of study vaccine or placebo. Has received a blood transfusion or blood products (including immunoglobulins) within 6 months before receipt of a study vaccine or placebo, or plans to receive a blood transfusion or blood products (including immunoglobulins) within 28 days following receipt of study vaccine or placebo. Has participated in another clinical study of an investigational product within 6 months before signing the informed consent, or plans to participate in another interventional clinical study at any time during the duration of the current clinical study. Participants enrolled in observational studies may be included; these will be reviewed on a case-by-case basis for approval by the Sponsor. 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V181 High-Potency Level Group<br>Participants will receive a single 0.5mL subcutaneous (SC) dose of V181 High-Potency vaccine. | Biological: V181 High-Potency Level<br>* 0.5 mL SC dose of V181 High-Potency vaccine<br>|
| Experimental: V181 Mid-Potency Level Group<br>Participants will receive a single 0.5mL SC dose of V181 Mid-Potency vaccine. | Biological: V181 Mid-Potency Level<br>* 0.5 mL SC dose of V181 Mid-Potency vaccine<br>|
| Experimental: V181 Low-Potency Level Group<br>Participants will receive a single 0.5mL SC dose of V181 Low-Potency vaccine. | Biological: V181 Low-Potency Level<br>* 0.5 mL SC dose of V181 Low-Potency vaccine<br>|
| Placebo Comparator: Placebo<br>Participants will receive a single SC 0.5 mL dose of placebo. | Biological: Placebo<br>* 0.5 mL SC dose of placebo<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) | A dengue VRNT will be conducted to assess neutralizing antibody GMTs for each of the 4 dengue vaccine serotypes (DENV1, DENV2, DENV3, and DENV4) in specimens collected from participants on Day 28 post-vaccination. | 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 will be determined by the investigator. | Up to 28 days post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Solicited Injection-Site Adverse Events (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 injection-site AEs will include pain, erythema (redness), and swelling. | Up to 5 days post-vaccination | 
| Percentage of Participants With 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 will include rash, headache, fatigue (tiredness), myalgia (muscle pain), and arthralgia (joint pain). | Up to 28 days post-vaccination |