Study of the Safety and Immunogenicity of Reduced Doses of the US Yellow Fever Vaccine

Study Overview
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Brief Summary
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This is an open-label, randomized, exploratory study to evaluate the human immune response to reduced subcutaneous (SQ) dosing of Yellow Fever vaccine compared to the standard FDA approved subcutaneous vaccination dose. The current dose of the US FDA licensed Yellow Fever vaccine is approximately 55,000 plaque-forming unit(s) (PFU) in 0.5 mL administered SQ. Using the licensed dosage as standard, investigators are evaluating reduced doses of 1/5th (0.10 mL) and 1/10th (0.05 mL) Yellow Fever vaccine (YF-VAX).

Detailed Description
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Up to 150 individuals will be screened in order to randomize 90 eligible individuals to one of three groups: Group 1- YF-VAX® standard dose 0.5 mL SQ = 30 subjects; Group 2-0.10 mL (1/5th) SQ = 30 subjects; Group 3-0.05 mL (1/10th) SQ = 30 subjects.

Official Title
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An Exploratory, Pilot Study of the Safety and Immunogenicity of Reduced Doses of the US Yellow Fever Vaccine

Conditions
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Yellow Fever Vaccination Reaction

Intervention / Treatment
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* Biological: Yellow Fever Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and Females 18 to 50 years of age. In good health, as determined by pertinent medical history, physical examination, vital signs, and clinical safety laboratory evaluations. Female of child bearing potential: Has a negative pregnancy test and is willing to use a reliable form of contraception for the duration of the study after vaccination. Negative human immunodeficiency virus (HIV) antibody screen, seronegative for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (following HIV and hepatitis testing, subjects will be provided with counseling and referral for health care if any test is positive). Ability to comprehend and a willingness to sign an informed consent, which includes the Health Insurance Portability and Accountability Act (HIPAA) Authorization, and a separate consent form for HIV testing. Be willing to comply with all follow-up visits, testing, adverse event (AE) reporting, and completion of diary card. Exclusion Criteria: Receipt of any other investigational vaccine or investigational drug within 28 days prior to or after vaccination with YF-VAX® vaccine. Have had any known flavivirus disease or receipt of any flavivirus vaccine, licensed or investigational at any time; in addition to any yellow fever vaccine, these include; Japanese Encephalitis (JE), St. Louis Encephalitis, Tick Borne Encephalitis (TBE), West Nile, Dengue, Zika virus Anticipates receipt of any other vaccine within 28 days of YF-VAX®. Influenza vaccination will be permitted but not within 14 days of YF-VAX®. Acute or chronic medical conditions, or medications that, in the Principal Investigator's (PI) opinion, would impair the subject's ability to respond to vaccination. Hypersensitivity to any vaccine, eggs or egg products, or allergy to any component of the YF-VAX® (sorbitol, gelatin) or latex. Corticosteroids even ≥20 mg/day of prednisone for ≥ 2 weeks suppresses the immune system. Low-dose corticosteroid topical products and nasal sprays used sporadically (i.e. prn--according to circumstances) are permissible. History of immunosuppression, by any cause--primary or acquired immunodeficiencies, transplantation, malignant neoplasm, lymphoma, leukemia, thymoma, myasthenia gravis, radiation, immunosuppressive drugs, including antimetabolites, tumor necrosis factor (TNF)-alpha inhibitors (etanercept), interleukin-1 (IL-1) blocking agents and other monoclonal antibodies targeting immune cells (e.g., rituximab, alemtuzumab, etc), etc. Receipt of or anticipates receipt of/or donation of blood or blood products for 2 months after receipt of YF-VAX®. (Note: Blood banks require a minimum 2 week interval between the receipt of this FDA licensed vaccine and blood donations; however because of the blood collections in this study, an interval of 2 months is requested). Female: Pregnant (or planning to become pregnant) or breastfeeding for the duration of the study after receipt of YF-VAX®. Clinically significant abnormal laboratory tests (generally 2 times the upper limit of normal or as determined by the PI).

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: Health Services Research
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Dose (Group 1)<br>Yellow Fever vaccine standard dose, 0.5mL. | Biological: Yellow Fever Vaccine<br>* Administered subcutaneously once.<br>* Other names: YF-VAX;|
| Experimental: Fractional dose (Group 2)<br>Yellow Fever vaccine 1/5th standard dose, 0.1mL. | Biological: Yellow Fever Vaccine<br>* Administered subcutaneously once.<br>* Other names: YF-VAX;|
| Experimental: Fractional dose (Group 3)<br>Yellow Fever vaccine 1/10th standard dose, 0.05mL. | Biological: Yellow Fever Vaccine<br>* Administered subcutaneously once.<br>* Other names: YF-VAX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Incidence of Adverse Events of fractional doses vs standard dose of YF-VAX as determined by subject diary and clinical history and physical examination. The incidence of solicited and unsolicited adverse events will be analyzed. | Up to one year following vaccination. | 
| Neutralizing Antibody Response | Compare the neutralizing antibody response rate and mean of each ARM as determined by PRNT obtained at several time points. Fractional doses will be compared to the standard dose of YF-VAX. The primary data point is post vaccination day 28. | Up to one year following vaccination. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viremia | Compare the incidence and level of viremia and mean viral load by RT-PCR (copies/mL) of fractional doses vs standard dose. | First 14 days following vaccination. |