Study on an Investigational Yellow Fever Vaccine Compared With Stamaril in Adults in Europe and Asia

Study Overview
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Brief Summary
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VYF03 is a phase II, randomized, parallel-group prevention study with 2 arms, active-controlled (Stamaril), observer-blind, multi-center study to assess the non-inferiority of the immune response, in terms of seroconversion rates of the investigational vaccine candidate vYF to the licensed Stamaril, in adults aged 18 years up to 60 years in Europe (EU). The safety and immunogenicity profile of vYF in a cohort of Asian population of Chinese origin outside of China will also be described. The study will also assess the immunogenicity profiles and the safety profiles of vYF and Stamaril. Participants will be randomized in a 2:1 ratio to receive a single subcutaneous injection of either the vYF vaccine (380 participants in EU and 80 participants of Chinese origin in Asia) or Stamaril (190 participants in EU and 40 participants of Chinese origin in Asia), on Day 01. The duration of each participant's participation will be approximately 5 years.

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 Stamaril in Adults

Conditions
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Yellow Fever

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 up 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 (1) or abstinence (1) from at least 4 weeks prior to study intervention administration until at least 4 weeks (2) after study intervention administration. *18 to 60 years means from the day of the 18th birthday up to the day before the 60th birthday Not applicable for Finland Except for French participants which have to apply 12 weeks contraception after study intervention administration A female 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 the test will be repeated on D29 to confirm the participant is still not pregnant within 28 days of vaccine administration. - Informed consent form has been signed and dated (3) For participants aged less than 21 years in Singapore, an informed consent form has been signed and dated by both the participant and the parent(s) or another legally acceptable representative Able to attend all scheduled visits and to comply with all study procedures For participants enrolled in Asian countries as part of the additional cohort only: know Chinese origin, defined as having at least one biological parent of Chinese origin, and will be self-reported by the participant Exclusion Criteria: Participation at the time of study enrollment (or in the 4 weeks preceding the study vaccination) or planned participation during the first 2 years 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 2 years is permitted, assuming that it does not exclude participation in this study. 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 (prior to visit 4), except for influenza vaccination, which may be received at least 2 weeks before study vaccines (4). This exception includes all influenza vaccines including monovalent pandemic influenza vaccines. Previous vaccination against a FV 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. 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 any FV 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 HIV infection (5). Known history or laboratory evidence of hepatitis B or hepatitis C infection (6). Personal or 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. Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion. Chronic illness (7) 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 or 38°C). 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 planned administration 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. Except for Thai participants HIV Serology testing will be performed on all German participants if no evidence of seronegativity in the 90 days preceding vaccination Hepatitis B and Hepatitis C Serology testing will be performed on all German participants if no evidence of seronegativity in the 90 days preceding vaccination Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, auto-immune disorders, diabetes, psychiatric disorders or chronic infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 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 at Day 1 | Biological: Yellow fever vaccine (produced on serum-free Vero cells)<br>* Powder and diluent for suspension for injection - Subcutaneous<br>* Other names: vYF vaccine;|
| Active Comparator: Group 2<br>1 injection of Stamaril vaccine at Day 1 | Biological: Yellow fever vaccine<br>* Powder and diluent for suspension for injection - Subcutaneous<br>* Other names: Stamaril;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants in EU with seroconversion to YF virus in YF-naïve population | Seroconversion is defined as a fourfold increase in NAb titers: i) as compared to the Day 01 titers at each time point up to Month 6; ii) as compared to the last planned previous time point from Y1 onwards | Day 01, Day 11 in a subset of participants only, and Day 29, Month 6, and yearly from Year 1 to Year 5 | 
| Percentage of participants in EU and in Asia with seroprotection to YF virus | Seroprotection is defined as NAb titers ≥ 10 (1/dil) at the corresponding timepoint | Day 01, Day 11 in a subset of participants only, and Day 29, Month 6, and yearly from Year 1 to Year 5 | 
| Geometric Mean Titers (GMTs) of neutralizing antibodies against YF virus in all participants in EU and in Asia | Antibody titers are expressed as geometric mean titers | Day 01 and Day 11 in a subset of participants only, and Day 29, Month 6, and yearly from Year 1 to Year 5 | 
| Geometric Mean Titers Ratio (GMTRs) of neutralizing antibodies against YF virus in all participants in EU and in Asia | GMTRs Day 11/Day 01 (subset only), Day 29/Day 01, Month 6/Day 01, Year 1/Month 6, Year 2/Year 1, Year 3/Year 2, Year 4/Year 3, Year 5/Year 4 | Day 01 and Day 11 in a subset of participants only, and Day 29, Month 6, and yearly from Year 1 to Year 5 | 
| Number of participants in EU and in Asia with immediate adverse avents | Immediate adverse events are any unsolicited systemic adverse events reported in the 30 minutes after vaccination | Within 30 minutes after vaccination | 
| Number of participants in EU and in Asia with solicited injection site reactions | Solicited injection site reactions include injection site pain, erythema and swelling | Within 7 days after vaccination | 
| Number of participants in EU and in Asia with solicited systemic reactions | Solicited systemic reactions include fever, headache, malaise and myalgia | Within 14 days after vaccination | 
| Number of participants in EU and in Asia with unsolicited adverse events (AEs) | Unsolicited (spontaneously reported) AEs, not fulfilling criteria for solicited adverse reactions | Within 28 days after vaccination | 
| Number of participants in EU and in Asia with serious adverse events (SAEs) and adverse events of special interest (AESIs) | SAEs and AESIs | From Day 01 to Month 6 | 
| Number of participants in EU and in Asia with related SAEs and death | SAEs | From Day 01 up to Year 5 |