| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Prevention of yellow fever |
|
| E.1.1.1 | Medical condition in easily understood language |
| Prevention of yellow fever |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10048240 |
| E.1.2 | Term | Yellow fever |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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 |
|
| E.2.2 | Secondary objectives of the trial |
•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
•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
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 |
|
| E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria
apply:
. 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
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
- Percentage of participants in EU with seroconversion to YF virus in YF-naïve population: Seroconversion is defined as a four-fold increase in neutralizing antibody (NAb) titers as compared to the pre-vaccination value
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1/ Percentage of participants in EU and in Asia with seroconversion to
YF virus : 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
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
events : 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
events (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 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-2-3-4/ / Day 01, Day 11 in a subset of participants only, and Day 29, Month 6, and yearly from Year 1 to Year 5
5/ Within 30 minutes of vaccination
6/ Within 7 days of vaccination
7/ Within 14 days of vaccination
8/ Within 28 days of vaccination
9/ From Day 01 to Month 6
10/ From Day 01 up to Year 5 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Singapore |
| Thailand |
| Finland |
| France |
| Spain |
| Germany |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
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