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

NCT04142086 | Completed Phase 1 FDA Drug

• 2 other identifiers: VYF01U1111-1217-1958
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Yellow Fever (Healthy Volunteers)

Outcome Measures

Primary Outcomes (13)

• 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

Study Arms (4)

Group 1

EXPERIMENTAL

1 injection of vYF vaccine Dosage 1

Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 1 vYF vaccine

Group 2

EXPERIMENTAL

1 injection of vYF vaccine Dosage 2

Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 2 vYF vaccine

Group 3

EXPERIMENTAL

1 injection of vYF vaccine Dosage 3

Biological: Yellow fever vaccine (produced on serum-free Vero cells), Dosage 3 vYF vaccine

Group 4

ACTIVE COMPARATOR

1 injection of YF-VAX

Biological: Yellow fever vaccine

Interventions

Yellow fever vaccine (produced on serum-free Vero cells), Dosage 1 vYF vaccine BIOLOGICAL

Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous

Group 1

Yellow fever vaccine (produced on serum-free Vero cells), Dosage 2 vYF vaccine BIOLOGICAL

Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous

Group 2

Yellow fever vaccine (produced on serum-free Vero cells), Dosage 3 vYF vaccine BIOLOGICAL

Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous

Group 3

Yellow fever vaccine BIOLOGICAL

Pharmaceutical form: Powder and diluent for suspension for injection Route of administration: Subcutaneous

Also known as: YF-VAX

Group 4

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (1)

Investigational Site Number 8400001

Silver Spring, Maryland, 20910, United States

Location

Related Publications (1)

• Pagnon A, Carre C, Aguirre M, Chautard E, Gimenez S, Raynal F, Feroldi E, Scott P, Modjarrad K, Vangelisti M, Mantel N. Next generation yellow fever vaccine induces an equivalent immune and transcriptomic profile to the current vaccine: observations from a phase I randomised clinical trial. EBioMedicine. 2024 Oct;108:105332. doi: 10.1016/j.ebiom.2024.105332. Epub 2024 Sep 17.

  PMID: 39293214 DERIVED

Related Links

• VYF01 Plain Language Results Summary

MeSH Terms

Conditions

Yellow Fever

Interventions

Yellow Fever Vaccine

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Clinical Sciences & Operations

  Sanofi Pasteur, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: An observer-blind procedure is followed for the injection of vYF or YF-VAX. Neither the observer Investigator, nor the Sponsor, nor the participants know product is administered. The "vaccinator" is in charge of preparing and administering the products and is not authorized to collect any safety data.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2019
• First Posted: October 29, 2019
• Study Start: January 15, 2020
• Primary Completion: June 24, 2021
• Study Completion: June 24, 2021
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)