Study on an Investigational Yellow Fever Vaccine Compared With YF-VAX in Adults in the USA

Study Overview
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Brief Summary
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The primary objective of the study is to demonstrate the non-inferiority of the antibody response in terms of seroconversion rate 28 days after vaccine administration of one dose of yellow fever vaccine (vYF) compared to the antibody response after one dose of the YF-VAX control vaccine in yellow fever naïve participants. The secondary objectives of the study are: To describe the immune response to yellow fever in both vaccine groups before and after vYF or YF-VAX administration. To describe the safety profile of vYF vaccine in comparison to the safety profile of the control YF-VAX. To describe the biosafety profile of vYF in comparison to the biosafety profile of the control YF-VAX.

Detailed Description
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The duration of each participant's participation will be approximately 5 years.

Official Title
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Controlled Study of Immunogenicity and Safety of the Investigational vYF Candidate Vaccine in Comparison to YF-VAX in Adults

Conditions
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Yellow Fever (Healthy Volunteers)

Intervention / Treatment
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* Biological: Yellow fever vaccine (produced on serum-free Vero cells)
* Biological: Yellow fever vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years to 60 years on the day of inclusion. A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be postmenopausal for at least 1 year, or surgically sterile. OR Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination. A participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) before any dose of study intervention on Day 1 and will be repeated on Day 29 to confirm the participant is still not pregnant within the 28 days of vaccine administration. Informed consent form has been signed and dated. Able to attend all scheduled visits and to comply with all study procedures. Exclusion Criteria: Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy, or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). Known history of flavivirus infection. Known systemic hypersensitivity to any of the vaccine components, eggs, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances. Known history or laboratory evidence of human immunodeficiency virus infection. Known history of hepatitis B or hepatitis C seropositivity Personal or family history of thymic pathology (thymoma, thymectomy, or myasthenia). Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion, including malignancy, such as leukemia, or lymphoma. Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 100.4°F). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided. Administration of any anti-viral within 2 months preceding the vaccination and up to the 6 weeks following the vaccination Receipt of any vaccine in the 4 weeks preceding the study vaccination or planned receipt of any vaccine in the 4 weeks following the study vaccination except for influenza vaccination, which may be received at least 2 weeks before study vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines. Previous vaccination against a flavivirus disease at any time including YF with either the study vaccine or another vaccine. Receipt of immune globulins, blood, or blood-derived products in the past 6 months. Participation at the time of study enrollment (or in the 4 weeks preceding the study vaccination) or planned participation during the first year of the 5-year follow-up in another clinical study investigating a vaccine, drug, medical device, or medical procedure. Enrollment in another study after the first year is permitted (starting the first day of Year 2, and onwards), assuming it does not exclude participation in this study Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily. Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion. Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study. Planned travel in a YF endemic country within 6 months of investigational or control vaccine administration.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vYF<br>1 injection of vYF at Day 1 | Biological: Yellow fever vaccine (produced on serum-free Vero cells)<br>* Powder and diluent for suspension for injection Subcutaneous injection<br>|
| Active Comparator: YF-VAX<br>1 injection of YF-VAX at Day 1 | Biological: Yellow fever vaccine<br>* Powder and diluent for suspension for injection Subcutaneous injection<br>* Other names: YF-VAX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with seroconversion to YF virus at Day 29 | Seroconversion is defined as a 4-fold increase in neutralizing antibody titers as compared to the pre-vaccination value. | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with seroconversion to YF virus | Seroconversion is defined as a 4-fold increase in neutralizing antibody titers as compared to the pre-vaccination value (up to Month 6) or compared to the values at the preceding time point (from Year 1 onwards). | Day 1, Day 11, Day 29, Month 6, Year 1, Year 2, Year 3, Year 4, and Year 5 | 
| Percentage of participants with seroprotection to YF virus | Seroprotection is defined as neutralizing antibody titers ≥ threshold of 10 (1/dil). | Day 1, Day 11, Day 29, Month 6, Year 1, Year 2, Year 3, Year 4, and Year 5 | 
| Number of participants with immediate adverse events | Immediate adverse events are any unsolicited systemic adverse events reported in the 30 minutes after vaccination. | Within 30 minutes after vaccination | 
| Number of participants with solicited injection site reactions | Solicited injection site reactions include injection site pain, erythema and swelling. | Within 7 days after vaccination | 
| Number of participants with solicited systemic reactions | Solicited systemic reactions include fever, headache, malaise and myalgia. | Within 14 days after vaccination | 
| Number of participants with unsolicited adverse events | Unsolicited (spontaneously reported) adverse events not fulfilling criteria for solicited adverse reactions, including medically attended adverse events. | Within 28 days after vaccination | 
| Number of participants with adverse events of special interest |  | Within 6 months after vaccination | 
| Number of participants with serious adverse events | Serious adverse events include medically attended adverse events. | From Day 1 to Month 6 | 
| Number of participants with related serious adverse events and deaths | Related serious adverse events include medically attended adverse events. | From Day 1 to Year 5 | 
| Number of participants with out-of-range biochemistry and hematology test results | Participants with biochemistry and hematology values out of normal range (as per the laboratory performing the test) are considered. | Day 1 and Day 11 |