Study on an Investigational Yellow Fever Vaccine Compared With YF-VAX in Adults in the USA (VYF02)

Controlled Study of Immunogenicity and Safety of the Investigational vYF Candidate Vaccine in Comparison to YF-VAX in Adults

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy Volunteers; Yellow Fever
• Intervention / Treatment: Biological: Yellow fever vaccine (produced on serum-free Vero cells); Biological: Yellow fever vaccine

Detailed Description

The duration of each participant's participation will be approximately 5 years.

• Study Type: Interventional
• Enrollment (Actual): 568
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Emory University Decatur- Site Number : 8400005
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • Velocity Clinical Research- New Orleans Site Number : 8400008
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Bloomberg School of Public Health (JHSPH)- Site Number : 8400004
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Harvard University Medical School- Site Number : 8400002
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University- Site Number : 8400003
  • Nebraska
    • Omaha, Nebraska, United States, 681134
      • Meridian Clinical Research- Site Number : 8400009
  • New York
    • East Syracuse, New York, United States, 13057
      • SUNY Upstate Medical University Global Health Institute Site Number : 8400006
    • New York, New York, United States, 10016
      • New York University Langone Medical Center Site Number : 8400013
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.- Site Number : 8400010
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Velocity Clinical Research - Providence Site Number : 8400015
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • J Lewis Research Inc- Site Number : 8400012

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vYF; 1 injection of vYF at Day 1	Biological: Yellow fever vaccine (produced on serum-free Vero cells); Powder and diluent for suspension for injection Subcutaneous injection
Active Comparator: YF-VAX; 1 injection of YF-VAX at Day 1	Biological: Yellow fever vaccine; Powder and diluent for suspension for injection Subcutaneous injection; Other Names: YF-VAX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	28 days post dose 1 (Day 29)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 30 minutes post vaccination on Day 1
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.	Up to 7 days post vaccination (Day 8)
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.	Up to 14 days post vaccination (Day 15)
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.	Up to 28 days post vaccination (Day 29)
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.	From the first dose of study vaccine administration (Day 1) up to end of study, approximately 5 years
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.	Days 1, 11, 29, Month 6, Years 1 and 2
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.	Days 1, 11, 29, Month 6, Years 1 and 2
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.	Days 1, 11, 29, Month 6, Years 1 and 2
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.	Days 1, 11, 29, Month 6, Years 1 and 2
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.	From the first dose of study vaccine administration (Day 1) up to 6 months post vaccination, approximately up to Day 181
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.	From the first dose of study vaccine administration (Day 1) up to DBL date of 29 August 2024, approximately up to Day 1155
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.	Days 1 and 11
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.	Days 1 and 11

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi Pasteur, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): June 24, 2022
• Study Completion (Estimated): June 29, 2027

Study Registration Dates

• First Submitted: June 25, 2021
• First Submitted That Met QC Criteria: June 25, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Body Temperature Changes; Fever; Yellow Fever; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: VYF02 (Other Identifier: Sanofi Identifier); U1111-1261-5612 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No