Clinical trial NCT05011123: Study on an Investigational Yellow Fever Vaccine Compared With Stamaril in Adults in Europe and Asia
Official title: Controlled Study of Immunogenicity and Safety of the Investigational vYF Candidate Vaccine in Comparison to Stamaril in Adults
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Yellow Fever
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-08-18
Enrollment: 690
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Yellow Fever-naive Participants Who Achieved Seroconversion 28 Days Post Dose 1 Enrolled in European Union
timeFrame: 28 days post dose 1 (Day 29)
Secondary outcomes:
measure: Percentage of Participants Who Achieved Seroconversion 28 Days Post Dose 1 Enrolled in European Union
timeFrame: 28 days post dose 1 (Day 29)
measure: Percentage of Participants Who Achieved Seroconversion Enrolled in European Union and Asia
timeFrame: Days 1, 11, 29, Month 6, Years 1 and 2
measure: Percentage of Participants Who Achieved Seroprotection to Yellow Fever Virus Enrolled in European Union and Asia
timeFrame: Days 1, 11, 29, Month 6, Years 1 and 2
measure: Geometric Mean Titers (GMTs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia
timeFrame: Days 1, 11, 29, Month 6, Years 1 and 2
measure: Geometric Mean Titers Ratio (GMTRs) of Antibodies Against Yellow Fever Virus in Participants Enrolled in European Union and Asia
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 Any 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 1030
timeFrame: From the first dose of study vaccine administration (Day 1) up to DBL date of 01 August 2024, approximately up to Day 1030
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
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Investigational Site Number : 2460001
city: Tampere
country: Finland
facility: Investigational Site Number : 2460002
city: Turku
country: Finland
facility: Investigational Site Number : 2460003
city: Lyon
country: France
facility: Investigational Site Number : 2500008
city: Montpellier
country: France
facility: Investigational Site Number : 2500006
city: Nantes
country: France
facility: Investigational Site Number : 2500001
city: Nimes
country: France
facility: Investigational Site Number : 2500007
city: Paris
country: France
facility: Investigational Site Number : 2500009
city: Pierre Benite
country: France
facility: Investigational Site Number : 2500004
city: Berlin
country: Germany
facility: Investigational Site Number : 2760004
city: Hamburg
country: Germany
facility: Investigational Site Number : 2760001
city: München
country: Germany
facility: Investigational Site Number : 2760002
city: Rostock
country: Germany
facility: Investigational Site Number : 2760003
city: Singapore
country: Singapore
facility: Investigational Site Number : 7020002
city: Singapore
country: Singapore
facility: Investigational Site Number : 7020003
city: Singapore
country: Singapore
facility: Investigational Site Number : 7020001
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240004
state: Barcelona [Barcelona]
city: Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number : 7240003
state: Barcelona [Barcelona]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240002
state: Madrid, Comunidad De
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240001
city: Bangkok
country: Thailand
facility: Investigational Site Number : 7640001
city: Bangkok
country: Thailand
facility: Investigational Site Number : 7640002
city: Nonthaburi
country: Thailand
facility: Investigational Site Number : 7640003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: