Dose-ranging Study of an Investigational Yellow Fever Candidate Vaccine in Adults (VYF01)

Safety, Tolerability, and Immunogenicity Dose-ranging Study of the Investigational Yellow Fever Vacine (vYF) Candidate Vaccine in Adults

The primary objectives of the study are:

• To describe the safety profile of each of the 3 dosages of vYF and of YF-VAX® within the 28 days post-vaccination and up to the 6 months (Day 180) post-vaccination visit
• To describe the antibody responses elicited by each of the 3 dosages of vYF and by YF-VAX on Day 0 pre-vaccination and then on Day 10, Day 14, Day 28 and 6 months (Day 180) post-vaccination overall and by baseline flavivirus serostatus
• To quantify the detectable yellow fever (YF) vaccinal viremia in each vaccine groups (vYF and YF-VAX) in a subset of subjects on Day 0 visit, Day 1 visit, Day 3 visit, Day 5 visit, Day 7 visit, Day 10 visit, and Day 14 visit.

Study Overview

• Status: Completed
• Conditions: Yellow Fever (Healthy Volunteers)
• Intervention / Treatment: Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 1 vYF vaccine; Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 2 vYF vaccine; Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 3 vYF vaccine; Biological: Yellow fever vaccine

Detailed Description

Study duration per participant is approximately 6 months.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Investigational Site Number 8400001

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria :

• Aged 18 years up to 60 years on the day of inclusion
• Able to read and understand the Informed Consent Form which has been signed and dated
• Able to attend all scheduled visits and to comply with all trial procedures

Exclusion criteria:

• Participant is pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche , or post-menopausal for at least 1 year, or surgically sterile
• Participation at the time of study enrollment (or in the 4 weeks preceding the trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
• Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned receipt of any vaccine in the 4 weeks following the trial vaccination
• Previous vaccination against a flavivirus disease including YF with either the trial vaccine or another vaccine
• Receipt of immune globulins, blood, or blood-derived products in the past 6 months
• 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 trial 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 of family history of thymic pathology (thymoma, thymectomy, or myasthenia)
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Current alcohol abuse or drug addiction
• 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
• 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

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1; 1 injection of vYF vaccine Dosage 1	Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 1 vYF vaccine; Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous
EXPERIMENTAL: Group 2; 1 injection of vYF vaccine Dosage 2	Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 2 vYF vaccine; Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous
EXPERIMENTAL: Group 3; 1 injection of vYF vaccine Dosage 3	Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 3 vYF vaccine; Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous
ACTIVE_COMPARATOR: Group 4; 1 injection of YF-VAX	Biological: Yellow fever vaccine; Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous; Other Names: YF-VAX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with immediate adverse events	Immediate adverse events are any unsolicited systemic adverse events reported in the 30 minutes after vaccination	Within 30 minutes after vaccination
Number of participants with solicited injection site reactions	Solicited injection site reactions include injection site pain, erythema and swelling	Within 7 days after vaccination
Number of participants with solicited systemic reactions	Solicited systemic reactions include fever, headache, malaise, and myalgia	Within 14 days after vaccination
Number of participants with unsolicited adverse events	Unsolicited (spontaneously reported) adverse events not fulfilling criteria for solicited adverse reactions	Within 28 days after vaccination
Number of participants with Grade 3 fever	Grade 3 fever is defined as temperature ≥ 102.1°F	Within 28 days after vaccination
Number of participants with serious adverse events	Serious adverse events are collected throughout the study	From Day 0 to Day 180
Number of participants with hematology and biochemistry out-of-range test results	Hematology and biochemistry values that are out-of-range are assessed	From Day 0 to Day 14
Number of participants with YF and flavivirus viremia and out-of-normal-range biological test results in the event of severe fever, or suspicion of neurotropic disease or acute viscerotropic diseases	Investigators are provided with guidelines for recognition and assessment of potential viscerotropic and neurotropic events	Within 28 days after vaccination
Number of participants with seroconversion to YF virus	Seroconversion is defined as a fourfold increase in neutralizing antibody titers as compared to pre-vaccination value. Seroconversion is assessed from Day 0 (pre-vaccination) to Day 10, Day 14 and Day 28.	From Day 0 to Day 28
Number of participants with neutralizing antibody titers against YF virus above pre-defined threshold	Pre-defined threshold of 10 1/dilution	From Day 0 to Day 180
Geometric mean titers of neutralizing antibodies against YF virus	Geometric mean titer ratio Day 10/Day 0, Day 14/Day 0, Day 28/Day 0 and Day 180/Day 0	From Day 0 to Day 180
Number of participants with YF vaccinal viremia	Vaccinal viremia is measured by YF specific quantitative reverse transcription polymerase chain reaction (RT-PCR) assay in samples collected on Day 0, Day 1, Day 3, Day 5, Day 7, Day 10, and Day 14.	From Day 0 to Day 14
Level of YF vaccinal viremia	Vaccinal viremia is measured by YF specific quantitative RT-PCR assay in samples collected on Day 0, Day 1, Day 3, Day 5, Day 7, Day 10, and Day 14.	From Day 0 to Day 14

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 15, 2020
• Primary Completion (ACTUAL): June 24, 2021
• Study Completion (ACTUAL): June 24, 2021

Study Registration Dates

• First Submitted: October 25, 2019
• First Submitted That Met QC Criteria: October 25, 2019
• First Posted (ACTUAL): October 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Body Temperature Changes; Hemorrhagic Fevers, Viral; Fever; Yellow Fever; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: VYF01; U1111-1217-1958 (OTHER: UTN)

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