Clinical trial NCT04942210: Study on an Investigational Yellow Fever Vaccine Compared With YF-VAX in Adults in the USA
Official title: Controlled Study of Immunogenicity and Safety of the Investigational vYF Candidate Vaccine in Comparison to YF-VAX in Adults
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Yellow Fever
Healthy Volunteers
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-06-28
Enrollment: 568
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Yellow Fever (YF)-Naive Participants Who Achieved Seroconversion 28 Days Post Dose 1
timeFrame: 28 days post dose 1 (Day 29)
Secondary outcomes:
measure: Percentage of Participants Who Achieved Seroconversion
timeFrame: Days 1, 11, 29, Month 6, Years 1 and 2
measure: Percentage of Participants Who Achieved Seroprotection
timeFrame: Days 1, 11, 29, Month 6, Years 1 and 2
measure: Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus
timeFrame: Days 1, 11, 29, Month 6, Years 1 and 2
measure: Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus
timeFrame: Days 1, 11, 29, Month 6, Years 1 and 2
measure: Number of Participants With Unsolicited Systemic Adverse Events (AEs)
timeFrame: Up to 30 minutes post vaccination on Day 1
measure: Number of Participants With Solicited Injection Site Reactions
timeFrame: Up to 7 days post vaccination (Day 8)
measure: Number of Participants With Solicited Systemic Reactions
timeFrame: Up to 14 days post vaccination (Day 15)
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: Up to 28 days post vaccination (Day 29)
measure: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) up to 6 Months Post-Vaccination
timeFrame: From the first dose of study vaccine administration (Day 1) up to 6 months post vaccination, approximately up to Day 181
measure: Number of Participants With Serious Adverse Events and Deaths up to Day 1155
timeFrame: From the first dose of study vaccine administration (Day 1) up to DBL date of 29 August 2024, approximately up to Day 1155
measure: Number of Participants With Serious Adverse Events and Deaths Up to Year 5
timeFrame: From the first dose of study vaccine administration (Day 1) up to end of study, approximately 5 years
measure: Number of Participants With Out-of-Range Biochemistry Parameters
timeFrame: Days 1 and 11
measure: Number of Participants With Out-of-Range Hematology Parameters
timeFrame: Days 1 and 11
Other outcomes:
Locations:
city: Decatur
country: United States
facility: Emory University Decatur- Site Number : 8400005
state: Georgia
city: New Orleans
country: United States
facility: Velocity Clinical Research- New Orleans Site Number : 8400008
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Bloomberg School of Public Health (JHSPH)- Site Number : 8400004
state: Maryland
city: Boston
country: United States
facility: Harvard University Medical School- Site Number : 8400002
state: Massachusetts
city: Saint Louis
country: United States
facility: Saint Louis University- Site Number : 8400003
state: Missouri
city: Omaha
country: United States
facility: Meridian Clinical Research- Site Number : 8400009
state: Nebraska
city: East Syracuse
country: United States
facility: SUNY Upstate Medical University Global Health Institute Site Number : 8400006
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center Site Number : 8400013
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc.- Site Number : 8400010
state: New York
city: East Greenwich
country: United States
facility: Velocity Clinical Research - Providence Site Number : 8400015
state: Rhode Island
city: Salt Lake City
country: United States
facility: J Lewis Research Inc- Site Number : 8400012
state: Utah
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: