Yellow Fever
Conditions
Brief summary
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
The duration of each participant's participation will be approximately 5 years.
Interventions
Powder and diluent for suspension for injection - Subcutaneous
BIOLOGICALYellow fever vaccine
Powder and diluent for suspension for injection - Subcutaneous
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Investigators, Sponsor, and Study staff who conduct the safety assessment and the participant will not know which vaccine is administered. Only the study staff who prepare and administer the vaccine and are not involved with the safety evaluation ("vaccinator") will know which vaccine is administered.
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
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 1. Not applicable for Finland 2. 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) 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. 4. Except for Thai participants 5. HIV Serology testing will be performed on all German participants if no evidence of seronegativity in the 90 days preceding vaccination 6. 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 7. Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, auto-immune disorders, diabetes, psychiatric disorders or chronic infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Yellow Fever-naive Participants Who Achieved Seroconversion 28 Days Post Dose 1 Enrolled in European Union | 28 days post dose 1 (Day 29) | Seroconversion was defined as a 4-fold increase in Nab titers as compared to the pre-vaccination value. YF-naive participants (or negative) at baseline corresponded to participants with no detectable YF Ab titers before vaccination. The YF NAb titers were determined using a validated live virus microneutralization (MN) assay. Percentages are rounded off to the tenth decimal place. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Seroconversion 28 Days Post Dose 1 Enrolled in European Union | 28 days post dose 1 (Day 29) | Seroconversion was defined as a 4-fold increase in Nab titers as compared to the pre-vaccination value. The YF NAb titers were determined using a validated live virus MN assay. Percentages are rounded off to the tenth decimal place. |
| Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | Days 1, 11, 29, Month 6, Years 1 and 2 | Seroconversion was defined as a 4-fold increase in Nab titers as compared to the pre-vaccination value: as compared to the Day 1 titers at each timepoint up to Month 6; as compared to the last planned previous timepoint from Year 1 onwards. The YF NAb titers were determined using a validated live virus MN assay. Percentages are rounded off to the tenth decimal place. |
| Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Days 1, 11, 29, Month 6, Years 1 and 2 | Seroprotection was defined as NAb titers \>=threshold of 10 (1/dilution). YF-naive participants (or negative) at baseline corresponded to participants with no detectable YF Ab titers before vaccination. The YF NAb titers were determined using a validated live virus MN assay. Percentages are rounded off to the tenth decimal place. |
| Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Days 1, 11, 29, Month 6, Years 1 and 2 | GMTs of antibody against YF virus was measured using a validated live virus MN assay. |
| Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Days 1, 11, 29, Month 6, Years 1 and 2 | GMTs of antibody against YF virus was measured using a validated live virus MN assay. Ratio was calculated as post-vaccination titer at Days 11, 29 and Month 6 to pre-vaccination titer at Day 1; post-vaccination titer at Year 1 to pre-vaccination titer at Month 6; post-vaccination titer at Year 2 to pre-vaccination titer at Year 1. |
| Number of Participants With Unsolicited Systemic Adverse Events (AEs) | Up to 30 minutes post vaccination on Day 1 | An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, ie, pre-listed in the CRF in terms of diagnosis and onset window post-vaccination. |
| Number of Participants With Solicited Injection Site Reactions | Up to 7 days post vaccination (Day 8) | A solicited reaction was an "expected" adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF. An injection site reaction was an AR at and around the injection site of the study vaccine. |
| Number of Participants With Solicited Systemic Reactions | Up to 14 days post vaccination (Day 15) | A solicited reaction was an "expected" AR (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF. Solicited systemic reactions were systemic AEs observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF. |
| Number of Participants With Unsolicited Adverse Events | Up to 28 days post vaccination (Day 29) | An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, ie, pre-listed in the CRF in terms of diagnosis and onset window post-vaccination. |
| Number of Participants With Any Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) up to 6 Months Post-Vaccination | From the first dose of study vaccine administration (Day 1) up to 6 months post vaccination, approximately up to Day 181 | An SAE was any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An AESI (serious or non-serious) was defined as one of scientific and medical concern specific to the Sponsor's study intervention or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor could be appropriate. AESIs included serious hypersensitivity/allergic reactions, organ failure/serious viscerotropic events, serious neurologic events. |
| Number of Participants With Serious Adverse Events and Deaths up to Day 1030 | From the first dose of study vaccine administration (Day 1) up to DBL date of 01 August 2024, approximately up to Day 1030 | An SAE was any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. |
| Number of Participants With Serious Adverse Events and Deaths Up to Year 5 | From the first dose of study vaccine administration (Day 1) up to end of study, approximately 5 years | An SAE was any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. |
Countries
Finland, France, Germany, Singapore, Spain, Thailand
Contacts
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Participant flow
Recruitment details
This study was conducted at 23 sites in 6 countries in Europe and Asia from 07 October 2021 to 25 April 2022. Interim results are presented up to Year 2 follow-up, data base lock (DBL) date of 01 August 2024.
Pre-assignment details
A total of 690 participants were randomized in a 2:1 ratio to receive a single subcutaneous (SC) injection of either yellow fever vaccine (vYF) vaccine or Stamaril. A subset of participants enrolled in European Union (EU) and Asia at selected sites provided an additional post-vaccination blood sample on Day 11 to assess the early immune response elicited by both vaccines in terms of neutralizing antibody (Nab) titers.
Participants by arm
| Arm | Count |
|---|---|
| vYF 0.5 mL Participants received 1 dose of vYF vaccine 0.5 mL as a SC injection on Day 1. | 455 |
| Stamaril 0.5 mL Participants received 1 dose of Stamaril vaccine 0.5 mL as a SC injection on Day 1. | 235 |
| Total | 690 |
Baseline characteristics
| Characteristic | vYF 0.5 mL | Stamaril 0.5 mL | Total |
|---|---|---|---|
| Age, Continuous | 37.1 Years STANDARD_DEVIATION 11.76 | 37.1 Years STANDARD_DEVIATION 11.51 | 37.1 Years STANDARD_DEVIATION 11.67 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 85 Participants | 43 Participants | 128 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Multiple origin | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 356 Participants | 187 Participants | 543 Participants |
| Sex: Female, Male Female | 253 Participants | 136 Participants | 389 Participants |
| Sex: Female, Male Male | 202 Participants | 99 Participants | 301 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 454 | 0 / 235 |
| other Total, other adverse events | 266 / 454 | 141 / 235 |
| serious Total, serious adverse events | 11 / 454 | 11 / 235 |
Outcome results
Primary
Percentage of Yellow Fever-naive Participants Who Achieved Seroconversion 28 Days Post Dose 1 Enrolled in European Union
Seroconversion was defined as a 4-fold increase in Nab titers as compared to the pre-vaccination value. YF-naive participants (or negative) at baseline corresponded to participants with no detectable YF Ab titers before vaccination. The YF NAb titers were determined using a validated live virus microneutralization (MN) assay. Percentages are rounded off to the tenth decimal place.
Time frame: 28 days post dose 1 (Day 29)
Population: The per-protocol analysis set (PPAS) was a subset of the full analysis set (FAS). The FAS included the subset of randomized participants who received at least 1 dose of the study vaccine or control vaccine and had a valid post-vaccination blood sample result. Only YF-naive participants enrolled in EU with data collected are reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| vYF 0.5 mL | Percentage of Yellow Fever-naive Participants Who Achieved Seroconversion 28 Days Post Dose 1 Enrolled in European Union | 98.1 percentage of participants |
| Stamaril 0.5 mL | Percentage of Yellow Fever-naive Participants Who Achieved Seroconversion 28 Days Post Dose 1 Enrolled in European Union | 99.4 percentage of participants |
95% CI: [-3.4, 1.8]
Secondary
Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia
GMTs of antibody against YF virus was measured using a validated live virus MN assay.
Time frame: Days 1, 11, 29, Month 6, Years 1 and 2
Population: FAS: subset of randomized participants who received at least 1 dose of study vaccine or control vaccine and had a valid post-vaccination blood sample result. Day 11: subset of participants enrolled in EU and Asia at selected sites who provided an additional post-vaccination blood sample on Day 11 to assess early immune response elicited by both vaccines in terms of Nab titers. Only participants enrolled in EU and Asia with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Day 1 | 5.62 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Day 11 | 26.6 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Day 29 | 2229 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Month 6 | 562 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Year 1 | 454 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Year 2 | 310 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Day 1 | 6.16 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Day 11 | 10.3 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Day 29 | 1204 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Month 6 | 495 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Year 1 | 303 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Year 2 | 168 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Year 1 | 245 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Day 1 | 6.18 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Day 1 | 5.63 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Day 11 | 52.3 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Month 6 | 398 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Day 29 | 1060 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Day 11 | 16.6 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Month 6 | 425 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Year 2 | 143 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Year 1 | 420 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Day 29 | 1167 titer |
| Stamaril 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Year 2 | 349 titer |
Secondary
Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia
GMTs of antibody against YF virus was measured using a validated live virus MN assay. Ratio was calculated as post-vaccination titer at Days 11, 29 and Month 6 to pre-vaccination titer at Day 1; post-vaccination titer at Year 1 to pre-vaccination titer at Month 6; post-vaccination titer at Year 2 to pre-vaccination titer at Year 1.
Time frame: Days 1, 11, 29, Month 6, Years 1 and 2
Population: FAS: subset of randomized participants who received at least 1 dose of study vaccine or control vaccine and had a valid post-vaccination blood sample result. Day 11: subset of participants enrolled in EU and Asia at selected sites who provided an additional post-vaccination blood sample on Day 11 to assess early immune response elicited by both vaccines in terms of Nab titers. Only participants enrolled in EU and Asia with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Day 11/Day 1 | 3.12 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Day 29/Day 1 | 206 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Month 6/Day 1 | 52.3 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Year 1/Month 6 | 0.810 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Year 2/Year 1 | 0.655 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Day 11/Day 1 | 1.31 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Day 29/Day 1 | 105 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Month 6/Day 1 | 43.1 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Year 1/Month 6 | 0.607 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Year 2/Year 1 | 0.542 ratio |
| Stamaril 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Month 6/Day 1 | 36.9 ratio |
| Stamaril 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Day 11/Day 1 | 4.92 ratio |
| Stamaril 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Day 11/Day 1 | 2.05 ratio |
| Stamaril 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Day 29/Day 1 | 90.9 ratio |
| Stamaril 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Year 2/Year 1 | 0.585 ratio |
| Stamaril 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Month 6/Day 1 | 36.7 ratio |
| Stamaril 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Day 29/Day 1 | 109 ratio |
| Stamaril 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Year 1/Month 6 | 0.993 ratio |
| Stamaril 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | Asia: Year 1/Month 6 | 0.601 ratio |
| Stamaril 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia | EU: Year 2/Year 1 | 0.822 ratio |
Secondary
Number of Participants With Any Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) up to 6 Months Post-Vaccination
An SAE was any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An AESI (serious or non-serious) was defined as one of scientific and medical concern specific to the Sponsor's study intervention or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor could be appropriate. AESIs included serious hypersensitivity/allergic reactions, organ failure/serious viscerotropic events, serious neurologic events.
Time frame: From the first dose of study vaccine administration (Day 1) up to 6 months post vaccination, approximately up to Day 181
Population: The SafAS included all participants who received at least 1 dose of the study vaccines.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| vYF 0.5 mL | Number of Participants With Any Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) up to 6 Months Post-Vaccination | SAEs | 6 Participants |
| vYF 0.5 mL | Number of Participants With Any Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) up to 6 Months Post-Vaccination | AESIs | 0 Participants |
| Stamaril 0.5 mL | Number of Participants With Any Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) up to 6 Months Post-Vaccination | SAEs | 8 Participants |
| Stamaril 0.5 mL | Number of Participants With Any Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) up to 6 Months Post-Vaccination | AESIs | 1 Participants |
Secondary
Number of Participants With Serious Adverse Events and Deaths up to Day 1030
An SAE was any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event.
Time frame: From the first dose of study vaccine administration (Day 1) up to DBL date of 01 August 2024, approximately up to Day 1030
Population: The SafAS included all participants who received at least 1 dose of the study vaccines.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| vYF 0.5 mL | Number of Participants With Serious Adverse Events and Deaths up to Day 1030 | SAEs | 11 Participants |
| vYF 0.5 mL | Number of Participants With Serious Adverse Events and Deaths up to Day 1030 | Deaths | 0 Participants |
| Stamaril 0.5 mL | Number of Participants With Serious Adverse Events and Deaths up to Day 1030 | SAEs | 11 Participants |
| Stamaril 0.5 mL | Number of Participants With Serious Adverse Events and Deaths up to Day 1030 | Deaths | 0 Participants |
Secondary
Number of Participants With Serious Adverse Events and Deaths Up to Year 5
An SAE was any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event.
Time frame: From the first dose of study vaccine administration (Day 1) up to end of study, approximately 5 years
Secondary
Number of Participants With Solicited Injection Site Reactions
A solicited reaction was an expected adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF. An injection site reaction was an AR at and around the injection site of the study vaccine.
Time frame: Up to 7 days post vaccination (Day 8)
Population: The SafAS included all participants who received at least 1 dose of the study vaccines. Only participants with data collected are reported.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| vYF 0.5 mL | Number of Participants With Solicited Injection Site Reactions | 152 Participants |
| Stamaril 0.5 mL | Number of Participants With Solicited Injection Site Reactions | 50 Participants |
Secondary
Number of Participants With Solicited Systemic Reactions
A solicited reaction was an expected AR (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF. Solicited systemic reactions were systemic AEs observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF.
Time frame: Up to 14 days post vaccination (Day 15)
Population: The SafAS included all participants who received at least 1 dose of the study vaccines. Only participants with data collected are reported.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| vYF 0.5 mL | Number of Participants With Solicited Systemic Reactions | 222 Participants |
| Stamaril 0.5 mL | Number of Participants With Solicited Systemic Reactions | 126 Participants |
Secondary
Number of Participants With Unsolicited Adverse Events
An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, ie, pre-listed in the CRF in terms of diagnosis and onset window post-vaccination.
Time frame: Up to 28 days post vaccination (Day 29)
Population: The SafAS included all participants who received at least 1 dose of the study vaccines.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| vYF 0.5 mL | Number of Participants With Unsolicited Adverse Events | 138 Participants |
| Stamaril 0.5 mL | Number of Participants With Unsolicited Adverse Events | 68 Participants |
Secondary
Number of Participants With Unsolicited Systemic Adverse Events (AEs)
An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, ie, pre-listed in the CRF in terms of diagnosis and onset window post-vaccination.
Time frame: Up to 30 minutes post vaccination on Day 1
Population: The safety analysis set (SafAS) included all participants who received at least 1 dose of the study vaccines.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| vYF 0.5 mL | Number of Participants With Unsolicited Systemic Adverse Events (AEs) | 0 Participants |
| Stamaril 0.5 mL | Number of Participants With Unsolicited Systemic Adverse Events (AEs) | 0 Participants |
Secondary
Percentage of Participants Who Achieved Seroconversion 28 Days Post Dose 1 Enrolled in European Union
Seroconversion was defined as a 4-fold increase in Nab titers as compared to the pre-vaccination value. The YF NAb titers were determined using a validated live virus MN assay. Percentages are rounded off to the tenth decimal place.
Time frame: 28 days post dose 1 (Day 29)
Population: The FAS included the subset of randomized participants who received at least 1 dose of the study vaccine or control vaccine and had a valid post-vaccination blood sample result. Only participants enrolled in EU with data collected are reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion 28 Days Post Dose 1 Enrolled in European Union | 95.9 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroconversion 28 Days Post Dose 1 Enrolled in European Union | 96.8 percentage of participants |
95% CI: [-4, 3]
Secondary
Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia
Seroconversion was defined as a 4-fold increase in Nab titers as compared to the pre-vaccination value: as compared to the Day 1 titers at each timepoint up to Month 6; as compared to the last planned previous timepoint from Year 1 onwards. The YF NAb titers were determined using a validated live virus MN assay. Percentages are rounded off to the tenth decimal place.
Time frame: Days 1, 11, 29, Month 6, Years 1 and 2
Population: FAS: subset of randomized participants who received at least 1 dose of study vaccine or control vaccine and had a valid post-vaccination blood sample result. Day 11: subset of participants enrolled in EU and Asia at selected sites who provided an additional post-vaccination blood sample on Day 11 to assess early immune response elicited by both vaccines in terms of Nab titers. Only participants enrolled in EU and Asia with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | EU: Day 11 | 30.4 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | EU: Day 29 | 95.9 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | EU: Month 6 | 95.8 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | EU: Year 1 | 3.2 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | EU: Year 2 | 0.9 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | Asia: Day 11 | 5.1 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | Asia: Day 29 | 87.2 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | Asia: Month 6 | 85.7 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | Asia: Year 1 | 1.3 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | Asia: Year 2 | 1.3 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | Asia: Month 6 | 100 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | EU: Day 11 | 63.6 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | Asia: Day 11 | 33.3 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | EU: Day 29 | 96.8 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | Asia: Year 2 | 2.5 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | EU: Month 6 | 95.2 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | Asia: Day 29 | 97.6 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | EU: Year 1 | 4.4 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | Asia: Year 1 | 0 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia | EU: Year 2 | 3.0 percentage of participants |
Secondary
Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia
Seroprotection was defined as NAb titers \>=threshold of 10 (1/dilution). YF-naive participants (or negative) at baseline corresponded to participants with no detectable YF Ab titers before vaccination. The YF NAb titers were determined using a validated live virus MN assay. Percentages are rounded off to the tenth decimal place.
Time frame: Days 1, 11, 29, Month 6, Years 1 and 2
Population: FAS: subset of randomized participants who received at least 1 dose of study vaccine or control vaccine and had a valid post-vaccination blood sample result. Day 11: subset of participants enrolled in EU and Asia at selected sites who provided an additional post-vaccination blood sample on Day 11 to assess early immune response elicited by both vaccines in terms of Nab titers. Only participants enrolled in EU and Asia with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Day 1 | 4.3 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Day 11 | 48.2 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Day 29 | 98.6 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Month 6 | 98.1 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Year 1 | 98.5 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Year 2 | 98.5 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Day 1 | 6.4 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Day 11 | 28.2 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Day 29 | 96.2 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Month 6 | 96.1 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Year 1 | 94.8 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Year 2 | 96.0 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Year 1 | 100 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Day 1 | 7.9 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Day 1 | 7.1 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Day 11 | 81.8 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Month 6 | 100 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Day 29 | 99.5 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Day 11 | 66.7 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Month 6 | 100 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Year 2 | 100 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Year 1 | 99.5 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | Asia: Day 29 | 100 percentage of participants |
| Stamaril 0.5 mL | Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia | EU: Year 2 | 100 percentage of participants |