Dose-ranging Study of an Investigational Yellow Fever Candidate Vaccine in Adults

Study Overview
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Brief Summary
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The primary objectives of the study are: To describe the safety profile of each of the 3 dosages of vYF and of YF-VAX® within the 28 days post-vaccination and up to the 6 months (Day 180) post-vaccination visit To describe the antibody responses elicited by each of the 3 dosages of vYF and by YF-VAX on Day 0 pre-vaccination and then on Day 10, Day 14, Day 28 and 6 months (Day 180) post-vaccination overall and by baseline flavivirus serostatus To quantify the detectable yellow fever (YF) vaccinal viremia in each vaccine groups (vYF and YF-VAX) in a subset of subjects on Day 0 visit, Day 1 visit, Day 3 visit, Day 5 visit, Day 7 visit, Day 10 visit, and Day 14 visit.

Detailed Description
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Study duration per participant is approximately 6 months.

Official Title
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Safety, Tolerability, and Immunogenicity Dose-ranging Study of the Investigational Yellow Fever Vacine (vYF) Candidate Vaccine 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), Dosage 1 vYF vaccine
* Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 2 vYF vaccine
* Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 3 vYF vaccine
* Biological: Yellow fever vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Aged 18 years up to 60 years on the day of inclusion Able to read and understand the Informed Consent Form which has been signed and dated Able to attend all scheduled visits and to comply with all trial procedures Exclusion criteria: Participant is pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche , or post-menopausal for at least 1 year, or surgically sterile Participation at the time of study enrollment (or in the 4 weeks preceding the trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned receipt of any vaccine in the 4 weeks following the trial vaccination Previous vaccination against a flavivirus disease including YF with either the trial vaccine or another vaccine Receipt of immune globulins, blood, or blood-derived products in the past 6 months 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 trial 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 of family history of thymic pathology (thymoma, thymectomy, or myasthenia) Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily Current alcohol abuse or drug addiction 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 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 The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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: Group 1<br>1 injection of vYF vaccine Dosage 1 | Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 1 vYF vaccine<br>* Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous<br>|
| Experimental: Group 2<br>1 injection of vYF vaccine Dosage 2 | Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 2 vYF vaccine<br>* Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous<br>|
| Experimental: Group 3<br>1 injection of vYF vaccine Dosage 3 | Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 3 vYF vaccine<br>* Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous<br>|
| Active Comparator: Group 4<br>1 injection of YF-VAX | Biological: Yellow fever vaccine<br>* Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous<br>* Other names: YF-VAX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Within 28 days after vaccination | 
| Number of participants with Grade 3 fever | Grade 3 fever is defined as temperature ≥ 102.1°F | Within 28 days after vaccination | 
| Number of participants with serious adverse events | Serious adverse events are collected throughout the study | From Day 0 to Day 180 | 
| Number of participants with hematology and biochemistry out-of-range test results | Hematology and biochemistry values that are out-of-range are assessed | From Day 0 to Day 14 | 
| Number of participants with YF and flavivirus viremia and out-of-normal-range biological test results in the event of severe fever, or suspicion of neurotropic disease or acute viscerotropic diseases | Investigators are provided with guidelines for recognition and assessment of potential viscerotropic and neurotropic events | Within 28 days after vaccination | 
| Number of participants with seroconversion to YF virus | Seroconversion is defined as a fourfold increase in neutralizing antibody titers as compared to pre-vaccination value. Seroconversion is assessed from Day 0 (pre-vaccination) to Day 10, Day 14 and Day 28. | From Day 0 to Day 28 | 
| Number of participants with neutralizing antibody titers against YF virus above pre-defined threshold | Pre-defined threshold of 10 1/dilution | From Day 0 to Day 180 | 
| Geometric mean titers of neutralizing antibodies against YF virus | Geometric mean titer ratio Day 10/Day 0, Day 14/Day 0, Day 28/Day 0 and Day 180/Day 0 | From Day 0 to Day 180 | 
| Number of participants with YF vaccinal viremia | Vaccinal viremia is measured by YF specific quantitative reverse transcription polymerase chain reaction (RT-PCR) assay in samples collected on Day 0, Day 1, Day 3, Day 5, Day 7, Day 10, and Day 14. | From Day 0 to Day 14 | 
| Level of YF vaccinal viremia | Vaccinal viremia is measured by YF specific quantitative RT-PCR assay in samples collected on Day 0, Day 1, Day 3, Day 5, Day 7, Day 10, and Day 14. | From Day 0 to Day 14 |