Healthy Volunteers, Yellow Fever
Conditions
Brief summary
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
The duration of each participant's participation will be approximately 5 years.
Interventions
Powder and diluent for suspension for injection Subcutaneous injection
BIOLOGICALYellow fever vaccine
Powder and diluent for suspension for injection Subcutaneous injection
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
The study will be performed in a modified double-blind fashion: Investigators, Sponsor, and study staff who conduct the safety assessment and the participant will not know which vaccine is administered.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Yellow Fever (YF)-Naive Participants Who Achieved Seroconversion 28 Days Post Dose 1 | 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 antibody (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 | 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: compared to the Day 1 titers at each timepoint up to Month 6; and 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 | Days 1, 11, 29, Month 6, Years 1 and 2 | Seroprotection was defined as NAb titers \>=threshold of 10 (1/dilution). 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 | 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 | 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 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 1155 | From the first dose of study vaccine administration (Day 1) up to DBL date of 29 August 2024, approximately up to Day 1155 | 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. |
| Number of Participants With Out-of-Range Biochemistry Parameters | Days 1 and 11 | Blood samples were collected at specified timepoints for assessment of biochemistry parameters: alanine aminotransferase (ALT), aspartate transaminase (AST), creatine phosphokinase (CPK), alkaline phosphatase (ALP), bilirubin (accompanied by any increase in liver function test (LFT) and normal LFT), creatinine and C-reactive protein (CRP). The intensity grading scale for laboratory abnormalities was pre-specified in the protocol. Number of participants with out-of-range biochemistry parameters are presented. |
| Number of Participants With Out-of-Range Hematology Parameters | Days 1 and 11 | Blood samples were collected at specified timepoints for assessment of hematology parameters: red blood cell count (RBC), hematocrit, mean corpuscular volume (MCV), monocytes, basophils, hemoglobin (Hb), white blood cell count (WBC) (increase and decrease), neutrophils and lymphocytes (decrease), eosinophils, platelets (decrease). The intensity grading scale for laboratory abnormalities was pre-specified in the protocol. Number of participants with out-of-range hematology parameters are presented. |
Countries
United States
Contacts
STUDY_DIRECTORClinical Sciences & Operations
Sanofi Pasteur, a Sanofi Company
Participant flow
Recruitment details
This study was conducted at 11 sites in the United States of America from 01 July 2021 to 27 May 2022. Interim results are presented up to Year 2 follow-up, data base lock (DBL) date of 29 August 2024.
Pre-assignment details
A total of 568 participants were randomized in a 2:1 ratio to receive a single subcutaneous (SC) injection of either yellow fever vaccine (vYF) vaccine or YF-VAX. A subset of participants enrolled at some sites provided an additional post-vaccination blood sample on Day 11 to assess the immune response elicited by both vaccines in terms of neutralizing antibody (NAb) titers and biological safety parameters on Days 1 and 11.
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. | 382 |
| YF-VAX 0.5 mL Participants received 1 dose of YF-VAX vaccine 0.5 mL as a SC injection on Day 1. | 186 |
| Total | 568 |
Baseline characteristics
| Characteristic | vYF 0.5 mL | YF-VAX 0.5 mL | Total |
|---|---|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 11.87 | 39.3 years STANDARD_DEVIATION 11.88 | 39.7 years STANDARD_DEVIATION 11.87 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Asian | 15 Participants | 12 Participants | 27 Participants |
| Race/Ethnicity, Customized Black or African American | 93 Participants | 53 Participants | 146 Participants |
| Race/Ethnicity, Customized Multiple origin | 6 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Reported | 5 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 258 Participants | 112 Participants | 370 Participants |
| Sex: Female, Male Female | 234 Participants | 116 Participants | 350 Participants |
| Sex: Female, Male Male | 148 Participants | 70 Participants | 218 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 379 | 1 / 186 |
| other Total, other adverse events | 206 / 379 | 113 / 186 |
| serious Total, serious adverse events | 6 / 379 | 5 / 186 |
Outcome results
Primary
Percentage of Yellow Fever (YF)-Naive Participants Who Achieved Seroconversion 28 Days Post Dose 1
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 antibody (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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| vYF 0.5 mL | Percentage of Yellow Fever (YF)-Naive Participants Who Achieved Seroconversion 28 Days Post Dose 1 | 99.7 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Yellow Fever (YF)-Naive Participants Who Achieved Seroconversion 28 Days Post Dose 1 | 99.4 percentage of participants |
95% CI: [-1.2, 3.2]
Secondary
Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus
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: The FAS included 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: a subset of participants enrolled at some sites provided an additional post-vaccination blood sample on Day 11 to assess the immune response elicited by both vaccines in terms of NAb titers. Only participants 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 | Day 1 | 5.87 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus | Day 11 | 15.2 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus | Day 29 | 2540 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus | Month 6 | 544 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus | Year 1 | 405 titer |
| vYF 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus | Year 2 | 196 titer |
| YF-VAX 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus | Year 1 | 552 titer |
| YF-VAX 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus | Day 1 | 5.56 titer |
| YF-VAX 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus | Month 6 | 702 titer |
| YF-VAX 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus | Day 11 | 42.6 titer |
| YF-VAX 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus | Year 2 | 245 titer |
| YF-VAX 0.5 mL | Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus | Day 29 | 3004 titer |
Secondary
Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus
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: The FAS included 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: a subset of participants enrolled at some sites provided an additional post-vaccination blood sample on Day 11 to assess the immune response elicited by both vaccines in terms of NAb titers. Only participants 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 | Day 29/Day 1 | 227 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus | Year 1/Month 6 | 0.742 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus | Month 6/Day 1 | 49.6 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus | Year 2/Year 1 | 0.473 ratio |
| vYF 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus | Day 11/Day 1 | 2.16 ratio |
| YF-VAX 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus | Year 2/Year 1 | 0.426 ratio |
| YF-VAX 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus | Day 11/Day 1 | 5.57 ratio |
| YF-VAX 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus | Day 29/Day 1 | 280 ratio |
| YF-VAX 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus | Month 6/Day 1 | 66.3 ratio |
| YF-VAX 0.5 mL | Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus | Year 1/Month 6 | 0.777 ratio |
Secondary
Number of Participants With Out-of-Range Biochemistry Parameters
Blood samples were collected at specified timepoints for assessment of biochemistry parameters: alanine aminotransferase (ALT), aspartate transaminase (AST), creatine phosphokinase (CPK), alkaline phosphatase (ALP), bilirubin (accompanied by any increase in liver function test (LFT) and normal LFT), creatinine and C-reactive protein (CRP). The intensity grading scale for laboratory abnormalities was pre-specified in the protocol. Number of participants with out-of-range biochemistry parameters are presented.
Time frame: Days 1 and 11
Population: Analysis was performed on a subset of participants enrolled at some sites who provided an additional post-vaccination blood sample to assess the biological safety parameters on Days 1 and 11. Only participants with data collected on Days 1 and 11 are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: CRP | 5 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: ALT | 4 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: ALT | 6 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: AST | 3 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: AST | 5 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: CPK | 9 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: CPK | 7 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: ALP | 3 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: ALP | 2 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: Bilirubin (Any increase in LFT) | 0 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: Bilirubin (Any increase in LFT) | 0 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: Bilirubin (Normal LFT) | 1 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: Bilirubin (Normal LFT) | 1 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: Creatinine | 4 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: Creatinine | 8 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: CRP | 4 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: CRP | 4 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: CRP | 4 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: ALP | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: ALT | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: Bilirubin (Normal LFT) | 1 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: ALT | 1 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: Bilirubin (Any increase in LFT) | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: AST | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: Creatinine | 2 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: AST | 2 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: Bilirubin (Any increase in LFT) | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: CPK | 6 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: Creatinine | 2 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 11: CPK | 6 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: Bilirubin (Normal LFT) | 1 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Biochemistry Parameters | Day 1: ALP | 0 Participants |
Secondary
Number of Participants With Out-of-Range Hematology Parameters
Blood samples were collected at specified timepoints for assessment of hematology parameters: red blood cell count (RBC), hematocrit, mean corpuscular volume (MCV), monocytes, basophils, hemoglobin (Hb), white blood cell count (WBC) (increase and decrease), neutrophils and lymphocytes (decrease), eosinophils, platelets (decrease). The intensity grading scale for laboratory abnormalities was pre-specified in the protocol. Number of participants with out-of-range hematology parameters are presented.
Time frame: Days 1 and 11
Population: Analysis was performed on a subset of participants enrolled at some sites who provided an additional post-vaccination blood sample to assess the biological safety parameters on Days 1 and 11. Only participants with data collected on Days 1 and 11 are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Monocytes | 6 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: RBC | 11 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Hematocrit | 12 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Hematocrit | 10 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: MCV | 7 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: MCV | 5 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: RBC | 7 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Monocytes | 6 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Basophils | 0 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Basophils | 0 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Hb | 12 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Hb | 10 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: WBC increase | 2 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: WBC increase | 13 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: WBC decrease | 2 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: WBC decrease | 13 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Neutrophils decrease | 2 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Neutrophils decrease | 8 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Lymphocytes decrease | 0 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Lymphocytes decrease | 2 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Eosinophils | 1 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Eosinophils | 1 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Platelets decrease | 4 Participants |
| vYF 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Platelets decrease | 5 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Platelets decrease | 1 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: RBC | 4 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: WBC increase | 1 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: RBC | 5 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Lymphocytes decrease | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Hematocrit | 6 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: WBC increase | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Hematocrit | 5 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Eosinophils | 2 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: MCV | 3 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: WBC decrease | 1 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: MCV | 2 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Lymphocytes decrease | 1 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Monocytes | 1 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: WBC decrease | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Monocytes | 4 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Platelets decrease | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Basophils | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Neutrophils decrease | 1 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Basophils | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Eosinophils | 2 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 1: Hb | 7 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Neutrophils decrease | 3 Participants |
| YF-VAX 0.5 mL | Number of Participants With Out-of-Range Hematology Parameters | Day 11: Hb | 6 Participants |
Secondary
Number of Participants With Serious Adverse Events and Deaths up to Day 1155
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 29 August 2024, approximately up to Day 1155
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 1155 | SAEs | 6 Participants |
| vYF 0.5 mL | Number of Participants With Serious Adverse Events and Deaths up to Day 1155 | Deaths | 2 Participants |
| YF-VAX 0.5 mL | Number of Participants With Serious Adverse Events and Deaths up to Day 1155 | SAEs | 5 Participants |
| YF-VAX 0.5 mL | Number of Participants With Serious Adverse Events and Deaths up to Day 1155 | Deaths | 1 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 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 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 Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) up to 6 Months Post-Vaccination | AESIs | 0 Participants |
| YF-VAX 0.5 mL | Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) up to 6 Months Post-Vaccination | SAEs | 2 Participants |
| YF-VAX 0.5 mL | Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) up to 6 Months Post-Vaccination | AESIs | 0 Participants |
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 | 115 Participants |
| YF-VAX 0.5 mL | Number of Participants With Solicited Injection Site Reactions | 64 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 | 178 Participants |
| YF-VAX 0.5 mL | Number of Participants With Solicited Systemic Reactions | 102 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 | 99 Participants |
| YF-VAX 0.5 mL | Number of Participants With Unsolicited Adverse Events | 40 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) | 1 Participants |
| YF-VAX 0.5 mL | Number of Participants With Unsolicited Systemic Adverse Events (AEs) | 0 Participants |
Secondary
Percentage of Participants Who Achieved Seroconversion
Seroconversion was defined as a 4-fold increase in Nab titers as compared to the pre-vaccination value: compared to the Day 1 titers at each timepoint up to Month 6; and 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: The FAS included 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: a subset of participants enrolled at some sites provided an additional post-vaccination blood sample on Day 11 to assess the immune response elicited by both vaccines in terms of NAb titers. Only participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion | Day 29 | 97.8 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion | Year 1 | 4.4 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion | Month 6 | 94.7 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion | Year 2 | 1.4 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroconversion | Day 11 | 30.5 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Participants Who Achieved Seroconversion | Year 2 | 1.3 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Participants Who Achieved Seroconversion | Day 11 | 58.1 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Participants Who Achieved Seroconversion | Day 29 | 98.4 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Participants Who Achieved Seroconversion | Month 6 | 98.8 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Participants Who Achieved Seroconversion | Year 1 | 4.9 percentage of participants |
Secondary
Percentage of Participants Who Achieved Seroprotection
Seroprotection was defined as NAb titers \>=threshold of 10 (1/dilution). 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: The FAS included 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: a subset of participants enrolled at some sites provided an additional post-vaccination blood sample on Day 11 to assess the immune response elicited by both vaccines in terms of NAb titers. Only participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Day 1 | 6.2 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Day 11 | 39.0 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Day 29 | 99.5 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Month 6 | 98.8 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Year 1 | 97.5 percentage of participants |
| vYF 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Year 2 | 98.6 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Year 1 | 97.5 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Day 1 | 4.4 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Month 6 | 99.4 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Day 11 | 61.3 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Year 2 | 100 percentage of participants |
| YF-VAX 0.5 mL | Percentage of Participants Who Achieved Seroprotection | Day 29 | 99.5 percentage of participants |