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

Phase 2Active Not RecruitingNCT04942210

Sanofi Pasteur, a Sanofi Company568 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

568

Conditions

Yellow Fever Healthy Volunteers

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (11)

Emory University Decatur- Site Number : 8400005

Decatur, Georgia, United States

Velocity Clinical Research- New Orleans Site Number : 8400008

New Orleans, Louisiana, United States

Johns Hopkins Bloomberg School of Public Health (JHSPH)- Site Number : 8400004

Baltimore, Maryland, United States

Harvard University Medical School- Site Number : 8400002

Boston, Massachusetts, United States

Saint Louis University- Site Number : 8400003

St Louis, Missouri, United States

Meridian Clinical Research- Site Number : 8400009

Omaha, Nebraska, United States

SUNY Upstate Medical University Global Health Institute Site Number : 8400006

East Syracuse, New York, United States

New York University Langone Medical Center Site Number : 8400013

New York, New York, United States

Rochester Clinical Research, Inc.- Site Number : 8400010

Rochester, New York, United States

Velocity Clinical Research - Providence Site Number : 8400015

East Greenwich, Rhode Island, United States

...and 1 more locations

Outcomes

Primary Outcomes

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)

Secondary Outcomes

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

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

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

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

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

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)

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)

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)

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

Number of Participants With Serious Adverse Events and Deaths up to Day 1155

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

Number of Participants With Serious Adverse Events and Deaths Up to Year 5

Time frame: From the first dose of study vaccine administration (Day 1) up to end of study, approximately 5 years

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

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