Study on an Investigational Yellow Fever Vaccine Compared With YF-VAX in Adults in the USA

Phase 2

Active, not recruiting

Conditions: Yellow Fever
Healthy Volunteers

Interventions: Biological: Yellow fever vaccine
Biological: Yellow fever vaccine (produced on serum-free Vero cells)

Registration Number: NCT04942210

Lead Sponsor: Sanofi Pasteur, a Sanofi Company

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 568

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
YF-VAX	Yellow fever vaccine	1 injection of YF-VAX at Day 1
vYF	Yellow fever vaccine (produced on serum-free Vero cells)	1 injection of vYF at Day 1

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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 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.

Trial Locations

Locations (11): Emory University Decatur- Site Number : 8400005
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Decatur, Georgia, United States
Velocity Clinical Research- New Orleans Site Number : 8400008
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New Orleans, Louisiana, United States
Johns Hopkins Bloomberg School of Public Health (JHSPH)- Site Number : 8400004
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Baltimore, Maryland, United States
Harvard University Medical School- Site Number : 8400002
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Boston, Massachusetts, United States
Saint Louis University- Site Number : 8400003
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Saint Louis, Missouri, United States
Meridian Clinical Research- Site Number : 8400009
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Omaha, Nebraska, United States
SUNY Upstate Medical University Global Health Institute Site Number : 8400006
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East Syracuse, New York, United States
New York University Langone Medical Center Site Number : 8400013
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New York, New York, United States
Rochester Clinical Research, Inc.- Site Number : 8400010
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Rochester, New York, United States
Velocity Clinical Research - Providence Site Number : 8400015
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East Greenwich, Rhode Island, United States
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Emory University Decatur- Site Number : 8400005
🇺🇸Decatur, Georgia, United States