Controlled Study of Immunogenicity and Safety of the Investigational vYF Candidate Vaccine in Comparison to Stamaril® in Adults
- Trial ID
- 2022-502047-35-00
- Protocol
- VYF03
- Sponsor
- Sanofi Pasteur
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the **non-inferiority** of the antibody response in terms of seroconversion rates 28 days after the administration of one dose of the investigational vYF vaccine compared to the response after one dose of the control vaccine, Stamaril, in participants from the European Union who are naïve to **yellow fever**. This is clinically relevant as it evaluates the potential of the vYF vaccine to provide an effective immune response comparable to the established Stamaril vaccine, which is crucial for preventing yellow fever in populations at risk.
Secondary objectives include:
- Describing the antibody immune responses to yellow fever in both vaccine groups in Europe and Asia before and after administration at various time points, including Day 11 (in a subset of participants), Day 29, Month 6, and annually from Year 1 to Year 5.
- Describing the safety profile of the vYF vaccine in all participants in Europe and Asia, in comparison to the safety profile of the control vaccine, Stamaril.
Participants
The clinical trial for **yellow fever** involves a total of 120 participants, comprising both male and female subjects. The study population includes individuals aged between 18 and 60 years, ensuring a broad representation of adults. Participants were selected based on their ability to attend all scheduled visits and comply with study procedures. The trial includes individuals who are not pregnant or breastfeeding, with specific contraceptive requirements for females of childbearing potential. The health status of participants is generally healthy, with no significant comorbidities reported. Lifestyle considerations such as diet and physical activity are not specified, but participants are expected to maintain their usual habits throughout the study. The trial also includes a vulnerable population, ensuring a diverse cohort. Participants have provided informed consent, and those in Asian countries have self-reported Chinese origin as part of an additional cohort. The selection criteria ensure a comprehensive evaluation of the vaccine's efficacy across different demographics.
Plans and Procedures
The clinical trial is designed to evaluate the **immunogenicity** and safety of an investigational yellow fever vaccine, referred to as the vYF vaccine, in comparison to the established Stamaril vaccine. This study is a **randomized**, double-blind, controlled trial conducted in adults aged 18 to 60 years who are naive to yellow fever. The trial aims to demonstrate the non-inferiority of the antibody response, specifically the seroconversion rates, 28 days post-vaccination with the vYF vaccine compared to the Stamaril vaccine. The trial is expected to span from July 2021 to January 2027, with participant involvement lasting up to five years, including follow-up assessments.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, ability to comply with study procedures, and, for females of childbearing potential, a negative pregnancy test. The initial vaccination will occur on Day 01, followed by a series of follow-up visits to monitor the immune response and safety outcomes. These visits will include assessments at Day 29, Month 6, and annually up to Year 5. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any adverse events are addressed.
Participants may be withdrawn from the study early if they experience serious adverse events, fail to comply with study procedures, or if new information arises that affects their continued participation. The primary endpoint is the percentage of participants achieving seroconversion, defined as a four-fold increase in neutralizing antibody titers. Secondary endpoints include seroprotection rates, geometric mean titers, and the incidence of adverse events. The study is conducted under strict ethical guidelines, with informed consent obtained from all participants prior to enrollment.
Treatment
The clinical trial involves the administration of the **vYF vaccine**, which is an investigational product formulated as a **powder and solvent for solution for injection**. The active substance in this vaccine is the **yellow fever virus, strain VYF-247, live**. The vaccine is manufactured by Sanofi Pasteur and is administered via **subcutaneous use**. Each participant receives a single dose of 0.5 ml, with the maximum treatment period being one day. The vYF vaccine is not a pediatric formulation and is classified as a structurally diverse substance, specifically a vaccine.
The comparator treatment in this study is the **STAMARIL vaccine**, also produced by Sanofi Pasteur. This vaccine is provided as a **suspension for injection** in a pre-filled syringe. The active substance is the **yellow fever virus strain 17D-204 (live, attenuated)**. Similar to the vYF vaccine, STAMARIL is administered subcutaneously, with a single dose of 0.5 ml given to each participant. The treatment period is also limited to one day. STAMARIL serves as the control vaccine in this trial, allowing for the comparison of immunogenicity and safety between the investigational vYF vaccine and the established STAMARIL vaccine.
Efficacy
The efficacy of the investigational vYF vaccine will be assessed by comparing the **seroconversion** rates of participants to those receiving the Stamaril control vaccine. The primary endpoint is the percentage of participants in the EU with seroconversion to the yellow fever virus in a yellow fever-naïve population. Seroconversion is defined as a 4-fold increase in neutralizing antibody (NAb) titers compared to the pre-vaccination value. Secondary endpoints include the percentage of participants with seroconversion at various time points up to Month 6, seroprotection rates defined as NAb titers ≥ 10 (1/dil), and geometric mean titers (GMTs) of neutralizing antibodies.
Measurements will be taken at multiple time points, including Day 01, Day 11, Day 29, Month 6, Year 1, Year 2, Year 3, Year 4, and Year 5. The analysis will involve calculating the geometric mean titers ratio (GMTRs) at these intervals. Additionally, the study will monitor the number of participants experiencing immediate adverse events, solicited injection site reactions, solicited systemic reactions, unsolicited adverse events, serious adverse events (SAEs), and adverse events of special interest (AESIs). The trial is designed to demonstrate the non-inferiority of the vYF vaccine in terms of immunogenicity and safety compared to the Stamaril vaccine.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Aged 18 years up to 60 years on the day of inclusion. 18 to 60 years means from the day of the 18th birthday up to the day before the 60th birthday.
- Able to attend all scheduled visits and to comply with all study procedures
- 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.
- 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. (1) Not applicable for Finland (2) Except for French participants which have to apply 12 weeks contraception after study intervention administration
- Informed consent form has been signed and dated. 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.
- 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 (except for Thai participants). 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. HIV Serology testing will be performed on all German participants if no evidence of seronegativity in the 90 days preceding vaccination.
- Known history or laboratory evidence of hepatitis B or hepatitis C infection. 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.
- 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 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. Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, auto-immune disorders, diabetes, psychiatric disorders or chronic infection.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Finland | Not Recruiting | 02 Jul 2021 | 70 |
 France | Not Recruiting | 02 Jul 2021 | 190 |
 Germany | Not Recruiting | 02 Jul 2021 | 220 |
 Spain | Not Recruiting | 02 Jul 2021 | 90 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
vYF vaccine | Test | POWDER AND SOLVENT FOR SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 0.5 | 1 | PRD9970520 |
STAMARIL, poudre et solvant pour suspension injectable en seringue préremplie.
Vaccin de la fièvre jaune (Vivant). | Comparator | POUDRE ET SOLVANT POUR SUSPENSION INJECTABLE EN SERINGUE PRÉREMPLIE | SUBCUTANEOUS USE | 0.5 | 1 | PRD320004 |