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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi Pasteur

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

7 Oct 2021 → ongoing

Decision date (initial)

2023-03-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi Pasteur

External identifiers

EU CT number

2022-502047-35-00

EudraCT number

2020-005566-33

WHO UTN

U1111-1260-4650

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Prophylaxis, Others

To demonstrate the non-inferiority of the antibody response in terms of seroconversion rates 28 days after vaccine administration of one dose of vYF (administered on Day 01) compared to the antibody response after one dose of the Stamaril control vaccine (administered on Day 01) in participants enrolled in EU in YF-naïve participants

Secondary objectives 2

1. To describe the antibody immune responses to YF in both vaccine groups in EU and in Asia before (Day 01) and after (Day 11 in a subset of participants only, and Day 29, Month 6, and yearly from Year 1 to Year 5 in all participants) vYF or Stamaril administration
2. To describe the safety profile of vYF vaccine in all participants, in EU and in Asia, in comparison to the safety profile of the control Stamaril

Conditions and MedDRA coding

Yellow fever

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Aged 18 years up to 60 years on the day of inclusion. 18 to 60 years means from the day of the 18th birthday up to the day before the 60th birthday.
2. Able to attend all scheduled visits and to comply with all study procedures
3. 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.
4. 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. (1) Not applicable for Finland (2) Except for French participants which have to apply 12 weeks contraception after study intervention administration
5. Informed consent form has been signed and dated. 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.
6. 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 17

1. 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.
2. 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 (except for Thai participants). This exception includes all influenza vaccines including monovalent pandemic influenza vaccines.
3. Previous vaccination against a FV disease at any time including YF with either the study vaccine or another vaccine.
4. Receipt of immune globulins, blood, or blood-derived products in the past 6 months.
5. 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).
6. Known history of any FV infection.
7. 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.
8. Known history or laboratory evidence of HIV infection. HIV Serology testing will be performed on all German participants if no evidence of seronegativity in the 90 days preceding vaccination.
9. Known history or laboratory evidence of hepatitis B or hepatitis C infection. 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.
10. Personal or family history of thymic pathology (thymoma, thymectomy, or myasthenia).
11. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
12. Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion.
13. 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. Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, auto-immune disorders, diabetes, psychiatric disorders or chronic infection.
14. 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.
15. Administration of any anti-viral within 2 months preceding the vaccination and planned administration up to the 6 weeks following the vaccination.
16. 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.
17. Planned travel in a YF endemic country within 6 months of investigational or control vaccine administration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 10

1. Percentage of participants in EU with seroconversion to YF virus in YF-naïve population. Seroconversion is defined as a 4-fold 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.
2. 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.
3. 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.
4. 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.
5. 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
6. Number of participants in EU and in Asia with solicited injection site reactions. Solicited injection site reactions include injection site pain, erythema and swelling.
7. Number of participants in EU and in Asia with solicited systemic reactions. Solicited systemic reactions include fever, headache, malaise and myalgia.
8. Number of participants in EU and in Asia with unsolicited adverse avents (AEs). Unsolicited (spontaneously reported) AEs, not fulfilling criteria for solicited adverse reactions.
9. Number of participants in EU and in Asia with serious adverse avents (SAEs) and adverse events of special interest (AESIs). SAEs and AESIs.
10. Number of participants in EU and in Asia with related SAEs and death.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi Pasteur

Sponsor organisation

Sanofi Pasteur

Address

14 Espace Henry Vallee

City

Lyon

Postcode

69007

Country

France

Scientific contact point

Organisation

Sanofi Pasteur

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi Pasteur

Contact name

Clinical Sciences and Operations

Third parties 6

Locations

4 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications