Study of a Dengue Vaccine (V180) in Healthy Adults (V180-001)

Study Overview
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Brief Summary
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This study will determine whether at least one formulation of an experimental dengue vaccine (V180) is safe and causes an immune response.

Official Title
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A Phase I Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Tetravalent Recombinant Subunit Dengue Vaccine (V180) in Healthy Adults

Conditions
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Dengue

Intervention / Treatment
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* Biological: Low-dose V180 with low-dose ISCOMATRIX™ adjuvant
* Biological: Low-dose V180 with medium-dose ISCOMATRIX™ adjuvant
* Biological: Medium-dose V180 (non-adjuvanted)
* Biological: Medium-dose V180 with low-dose ISCOMATRIX™ adjuvant
* Biological: Medium-dose V180 with medium-dose ISCOMATRIX™ adjuvant
* Biological: Medium-dose V180 with Alhydrogel™ adjuvant
* Biological: High-dose V180 (non-adjuvanted)
* Biological: High-dose V180 with low-dose ISCOMATRIX™ adjuvant
* Biological: High-dose V180 with medium-dose ISCOMATRIX™ adjuvant
* Biological: Low-dose V180 with high-dose ISCOMATRIX™ adjuvant
* Biological: Medium-dose V180 with high-dose ISCOMATRIX™ adjuvant
* Biological: High-dose V180 with high-dose ISCOMATRIX™ adjuvant
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Selected Inclusion Criteria: In good health Voluntarily agrees to participate by giving written informed consent Able to read, understand, and complete study questionnaires Able to complete all scheduled visits and comply with study procedures Access to a telephone Agrees to avoid unusual, vigorous exercise from 72 hours before any dose of study vaccine/placebo through 15 days after that dose Weighs ≥110 pounds (50 kg) and has a body mass index (BMI) of 19 to 32 kg/m^2 No fever (temperature ≥100.4°F/38.0°C) for 72 hours prior to vaccination Females of reproductive potential agree to remain abstinent or to use 2 acceptable methods of birth control from enrollment through 6 weeks after the last dose of study vaccine/placebo Selected Exclusion Criteria: History of receiving any flavivirus vaccine (e.g. Japanese encephalitis, tick-borne encephalitis, or yellow fever) or planned receipt of any such vaccine during the study period History of any flavivirus infection or serologic evidence of any flavivirus infection, including West Nile, dengue, yellow fever, Saint Louis encephalitis (if available), Kunjin, Murray Valley encephalitis, and Japanese encephalitis History of residence for a cumulative period of >1 year in a country where dengue, Japanese encephalitis virus, or yellow fever virus is common Planned travel to an area where dengue is common through 28 days after receiving the last dose of study vaccine/placebo Known hypersensitivity to any component of the dengue vaccine Abuse of drugs or alcohol within 12 months prior to screening Pregnant or breastfeeding, or expecting to conceive in the time from enrollment through 6 weeks after the last dose of study vaccine/placebo Positive serum test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and/or hepatitis C antibody Known, suspected, or a history of immunocompromise History of malignancy within 5 years prior to enrollment Poorly controlled diabetes mellitus Use of any immunosuppressive therapy (except topical and inhaled/nebulized steroids) Receipt of any licensed non-live vaccine within 14 days prior to the first dose of study vaccine/placebo or plans to receive a licensed non-live vaccine during the time between receiving the first dose and 28 days after receiving the last dose of study vaccine/placebo Receipt of any licensed live vaccine within 30 days prior to the first dose of study vaccine/placebo or plans to receive a licensed live vaccine during the time between receiving the first dose and 28 after receiving the last dose of study vaccine/placebo Received investigational drugs or vaccines within 2 months prior to the first dose of study vaccine/placebo History of receiving 1 or more doses of an investigational dengue vaccine Participation in another clinical study within 42 days prior to enrollment, or plans to participate in another clinical study from enrollment through 1 year after the last dose of study vaccine/placebo Planned donation of eggs or sperm from the time of enrollment through 28 days after the last dose of study vaccine/placebo Prior receipt of a blood transfusion or blood products within 6 months prior to the first dose of study vaccine/placebo Hospitalization for acute illness within 3 months prior to the first dose of vaccine/placebo

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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: Low-dose V180 with low-dose ISCOMATRIX™ adjuvant<br> | Biological: Low-dose V180 with low-dose ISCOMATRIX™ adjuvant<br>* Three 0.5-mL intramuscular doses of low-dose V180 containing low-dose ISCOMATRIX™ adjuvant at Months 0, 1, and 2<br>|
| Experimental: Low-dose V180 with medium-dose ISCOMATRIX™ adjuvant<br> | Biological: Low-dose V180 with medium-dose ISCOMATRIX™ adjuvant<br>* Three 0.5-mL intramuscular doses of low-dose V180 containing medium-dose ISCOMATRIX™ adjuvant at Months 0, 1, and 2<br>|
| Experimental: Medium-dose Non-adjuvanted V180<br> | Biological: Medium-dose V180 (non-adjuvanted)<br>* Three 0.5-mL intramuscular doses of medium-dose V180 with no adjuvant at Months 0, 1, and 2<br>|
| Experimental: Medium-dose V180 with low-dose ISCOMATRIX™ adjuvant<br> | Biological: Medium-dose V180 with low-dose ISCOMATRIX™ adjuvant<br>* Three 0.5-mL intramuscular doses of medium-dose V180 containing low-dose ISCOMATRIX™ adjuvant at Months 0, 1, and 2<br>|
| Experimental: Medium-dose V180 with medium-dose ISCOMATRIX™ adjuvant<br> | Biological: Medium-dose V180 with medium-dose ISCOMATRIX™ adjuvant<br>* Three 0.5-mL intramuscular doses of medium-dose V180 containing medium-dose ISCOMATRIX™ adjuvant at Months 0, 1, and 2<br>|
| Experimental: Medium-Dose V180 with Alhydrogel™ adjuvant<br> | Biological: Medium-dose V180 with Alhydrogel™ adjuvant<br>* Three 0.5-mL intramuscular doses of medium-dose V180 containing Alhydrogel™ adjuvant at Months 0, 1, and 2<br>|
| Experimental: High-dose Non-adjuvanted V180<br> | Biological: High-dose V180 (non-adjuvanted)<br>* Three 0.5-mL intramuscular doses of high-dose V180 with no adjuvant at Months 0, 1, and 2<br>|
| Experimental: High-dose V180 with low-dose ISCOMATRIX™ adjuvant<br> | Biological: High-dose V180 with low-dose ISCOMATRIX™ adjuvant<br>* Three 0.5-mL intramuscular doses of high-dose V180 containing low-dose ISCOMATRIX™ adjuvant at Months 0, 1, and 2<br>|
| Experimental: High-dose V180 with medium-dose ISCOMATRIX™ adjuvant<br> | Biological: High-dose V180 with medium-dose ISCOMATRIX™ adjuvant<br>* Three 0.5-mL intramuscular doses of high-dose V180 containing medium-dose ISCOMATRIX™ adjuvant at Months 0, 1, and 2<br>|
| Experimental: Low-dose V180 with high-dose ISCOMATRIX™ adjuvant<br> | Biological: Low-dose V180 with high-dose ISCOMATRIX™ adjuvant<br>* Three 0.5-mL intramuscular doses of low-dose V180 containing high-dose ISCOMATRIX™ adjuvant at Months 0, 1, and 2<br>|
| Experimental: Medium-dose V180 with high-dose ISCOMATRIX™ adjuvant<br> | Biological: Medium-dose V180 with high-dose ISCOMATRIX™ adjuvant<br>* Three 0.5-mL intramuscular doses of medium-dose V180 containing high-dose ISCOMATRIX™ adjuvant at Months 0, 1, and 2<br>|
| Experimental: High-dose V180 with high-dose ISCOMATRIX™ adjuvant<br> | Biological: High-dose V180 with high-dose ISCOMATRIX™ adjuvant<br>* Three 0.5-mL intramuscular doses of high-dose V180 containing high-dose ISCOMATRIX™ adjuvant at Months 0, 1, and 2<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Three 0.5-mL intramuscular doses of phosphate-buffered saline at Months 0, 1, and 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate for each serotype |  | 28 days postdose 3 (Day 84) | 
| Geometric mean titer (GMT) of virus neutralizing antibodies for each serotype |  | 28 days postdose 3 (Day 84) |