Study on an Investigational Yellow Fever Vaccine Compared With Stamaril in Adults in Europe and Asia

Yellow Fever Clinical Trial

Official title:

Controlled Study of Immunogenicity and Safety of the Investigational vYF Candidate Vaccine in Comparison to Stamaril in Adults

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05011123
• Other study ID #: VYF03
• Secondary ID: U1111-1260-46502
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 7, 2021
• Est. completion date: April 23, 2027

Study information

• Verified date: January 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

VYF03 is a phase II, randomized, parallel-group prevention study with 2 arms, active-controlled (Stamaril), observer-blind, multi-center study to assess the non-inferiority of the immune response, in terms of seroconversion rates of the investigational vaccine candidate vYF to the licensed Stamaril, in adults aged 18 years up to 60 years in Europe (EU).

The safety and immunogenicity profile of vYF in a cohort of Asian population of Chinese origin outside of China will also be described. The study will also assess the immunogenicity profiles and the safety profiles of vYF and Stamaril.

Participants will be randomized in a 2:1 ratio to receive a single subcutaneous injection of either the vYF vaccine (380 participants in EU and 80 participants of Chinese origin in Asia) or Stamaril (190 participants in EU and 40 participants of Chinese origin in Asia), on Day 01.

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

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 690
• Est. completion date: April 23, 2027
• Est. primary completion date: May 23, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

Inclusion Criteria:

• Aged 18 years up 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 (1) or abstinence (1) from at least 4 weeks prior to study intervention administration until at least 4 weeks (2) after study intervention administration.

*18 to 60 years means from the day of the 18th birthday up to the day before the 60th birthday

1. Not applicable for Finland

2. Except for French participants which have to apply 12 weeks contraception after study intervention administration A female 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 the test will be repeated on D29 to confirm the participant is still not pregnant within 28 days of vaccine administration.

• Informed consent form has been signed and dated (3)

3. For participants aged less than 21 years in Singapore, an informed consent form has been signed and dated by both the participant and the parent(s) or another legally acceptable representative

• Able to attend all scheduled visits and to comply with all study procedures

• For participants enrolled in Asian countries as part of the additional cohort only: know Chinese origin, defined as having at least one biological parent of Chinese origin, and will be self-reported by the participant

Exclusion Criteria:

Participation at the time of study enrollment (or in the 4 weeks preceding the study vaccination) or planned participation during the first 2 years 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 2 years is permitted, assuming that it does not exclude participation in this study.

• 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 (prior to visit 4), except for influenza vaccination, which may be received at least 2 weeks before study vaccines (4). This exception includes all influenza vaccines including monovalent pandemic influenza vaccines.

• Previous vaccination against a FV 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.

• 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 any FV 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 HIV infection (5).

• Known history or laboratory evidence of hepatitis B or hepatitis C infection (6).

• Personal or 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.

• Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion.

• Chronic illness (7) 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 or 38°C). 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 planned administration 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.

4. Except for Thai participants

5. HIV Serology testing will be performed on all German participants if no evidence of seronegativity in the 90 days preceding vaccination

6. Hepatitis B and Hepatitis C Serology testing will be performed on all German participants if no evidence of seronegativity in the 90 days preceding vaccination

7. Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, auto-immune disorders, diabetes, psychiatric disorders or chronic infection

Related Conditions & MeSH terms

• Fever
• Yellow Fever

Intervention

Biological:
• Yellow fever vaccine (produced on serum-free Vero cells)
Powder and diluent for suspension for injection - Subcutaneous
• Yellow fever vaccine
Powder and diluent for suspension for injection - Subcutaneous

Locations

Country	Name	City	State
Finland	Investigational Site Number : 2460001	Helsinki
Finland	Investigational Site Number : 2460002	Tampere
Finland	Investigational Site Number : 2460003	Turku
France	Investigational Site Number : 2500008	Lyon
France	Investigational Site Number : 2500006	Montpellier
France	Investigational Site Number : 2500001	Nantes
France	Investigational Site Number : 2500007	Nimes
France	Investigational Site Number : 2500009	Paris
France	Investigational Site Number : 2500004	Pierre Benite
Germany	Investigational Site Number : 2760004	Berlin
Germany	Investigational Site Number : 2760001	Hamburg
Germany	Investigational Site Number : 2760002	München
Germany	Investigational Site Number : 2760003	Rostock
Singapore	Investigational Site Number : 7020001	Singapore
Singapore	Investigational Site Number : 7020002	Singapore
Singapore	Investigational Site Number : 7020003	Singapore
Spain	Investigational Site Number : 7240001	Barcelona
Spain	Investigational Site Number : 7240004	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240003	Hospitalet de Llobregat	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240002	Madrid	Madrid, Comunidad De
Thailand	Investigational Site Number : 7640001	Bangkok
Thailand	Investigational Site Number : 7640002	Bangkok
Thailand	Investigational Site Number : 7640003	Nonthaburi

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

Finland,  France,  Germany,  Singapore,  Spain,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants in EU with seroconversion to YF virus in YF-naïve population	Seroconversion is defined as a 4-fold increase in neutralizing antibody (NAb) titers as compared to the pre-vaccination value	Day 29
Secondary	Percentage of participants in EU with seroconversion to YF virus in YF-naïve population	Seroconversion is defined as a fourfold increase in NAb titers: i) as compared to the Day 01 titers at each time point up to Month 6; ii) as compared to the last planned previous time point from Y1 onwards	Day 01, Day 11 in a subset of participants only, and Day 29, Month 6, and yearly from Year 1 to Year 5
Secondary	Percentage of participants in EU and in Asia with seroprotection to YF virus	Seroprotection is defined as NAb titers = 10 (1/dil) at the corresponding timepoint	Day 01, Day 11 in a subset of participants only, and Day 29, Month 6, and yearly from Year 1 to Year 5
Secondary	Geometric Mean Titers (GMTs) of neutralizing antibodies against YF virus in all participants in EU and in Asia	Antibody titers are expressed as geometric mean titers	Day 01 and Day 11 in a subset of participants only, and Day 29, Month 6, and yearly from Year 1 to Year 5
Secondary	Geometric Mean Titers Ratio (GMTRs) of neutralizing antibodies against YF virus in all participants in EU and in Asia	GMTRs Day 11/Day 01 (subset only), Day 29/Day 01, Month 6/Day 01, Year 1/Month 6, Year 2/Year 1, Year 3/Year 2, Year 4/Year 3, Year 5/Year 4	Day 01 and Day 11 in a subset of participants only, and Day 29, Month 6, and yearly from Year 1 to Year 5
Secondary	Number of participants in EU and in Asia with immediate adverse avents	Immediate adverse events are any unsolicited systemic adverse events reported in the 30 minutes after vaccination	Within 30 minutes after vaccination
Secondary	Number of participants in EU and in Asia with solicited injection site reactions	Solicited injection site reactions include injection site pain, erythema and swelling	Within 7 days after vaccination
Secondary	Number of participants in EU and in Asia with solicited systemic reactions	Solicited systemic reactions include fever, headache, malaise and myalgia	Within 14 days after vaccination
Secondary	Number of participants in EU and in Asia with unsolicited adverse events (AEs)	Unsolicited (spontaneously reported) AEs, not fulfilling criteria for solicited adverse reactions	Within 28 days after vaccination
Secondary	Number of participants in EU and in Asia with serious adverse events (SAEs) and adverse events of special interest (AESIs)	SAEs and AESIs	From Day 01 to Month 6
Secondary	Number of participants in EU and in Asia with related SAEs and death	SAEs	From Day 01 up to Year 5