Immunogenicity and Safety of Multiple Formulations of an Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With and Without Adjuvant in Healthy European Subjects Aged 6 to 35 Months - Immunogenicity and safety of different formulations of intramuscular swine-origin influenza vaccine

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-013858-32-FI
• Date of registration: 13/07/2009
• Prospective Registration: Yes
• Primary sponsor: Sanofi Pasteur SA
• Public title: Immunogenicity and Safety of Multiple Formulations of an Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With and Without Adjuvant in Healthy European Subjects Aged 6 to 35 Months - Immunogenicity and safety of different formulations of intramuscular swine-origin influenza vaccine
• Scientific title: Immunogenicity and Safety of Multiple Formulations of an Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With and Without Adjuvant in Healthy European Subjects Aged 6 to 35 Months - Immunogenicity and safety of different formulations of intramuscular swine-origin influenza vaccine
• Date of first enrolment: 14/09/2009
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-013858-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Finland

Key inclusion & exclusion criteria

Inclusion criteria:
All subjects
1) Aged 6 to 35 months on the day of inclusion
2) Informed consent form has been signed and dated by the parent(s) or other legally
acceptable representative
3) Subject and parent/legal representative are able to attend all scheduled visits and
to comply with all trial procedures
4) Completion of vaccination according to the national immunization schedule
Subjects =6 to <24 months of age
5) Born at full term of pregnancy (=37 weeks) and with a birth weight =2.5 kg

At V05 (M8) for antibody persistence assessment (amendment 2)
6) Having received two half doses of the 15 µg HA vaccine or of the
3.8 µg HA + AF03 vaccine
7) Addendum 1 to Informed Consent Form has been signed and dated by the
parent(s) or other legally acceptable representative

At V06, for subjects eligible for the Ab persistence evaluation who will receive the TIV (amendment 3):
8)Addendum 2 to Informed Consent Form has been signed by the subject’s parents/legal representative.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
All subjects
1) Participation in another clinical trial investigating a vaccine, drug, medical device,
or medical procedure in the 4 weeks preceding the first trial vaccination
2) Planned participation in another clinical trial during the present trial period
3) Receipt of any vaccine in the 4 weeks preceding the first trial vaccination
4) Planned receipt of any vaccine prior to the Day 42 blood sample
5) Receipt of blood or blood-derived products in the past 3 months, which might
interfere with assessment of the immune response
6) 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)
7) Seropositivity for Human Immunodeficiency Virus (HIV), Hepatitis B antigen, or
Hepatitis C as reported by parents/legal representative
8) Known systemic hypersensitivity to any of the vaccine components, or history of
a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine
containing any of the same substances
9) Thrombocytopenia, contraindicating IM vaccination as reported by parents/legal
representative
10) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion,
contraindicating IM vaccination
11) Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion
12) Family members of the Investigator or of the employees of the study center
13) Previous participation in a trial investigating a vaccine with the swine-origin
A/H1N1 influenza strain
14) Confirmed infection with the swine-origin A/H1N1 influenza strain (different
from the seasonal strain) in 2009
15) Febrile illness (temperature =38.0°C) or moderate or severe acute illness/infection
on the day of vaccination, according to Investigator judgment
16) Receipt of any allergy shots and/or seasonal allergy medication in the 7-day
period prior to enrollment (vaccination), or scheduled to receive any allergy shots
and/or seasonal allergy medication in the 7-day period after enrollment
(vaccination)
Subjects =6 to <24 months of age
17) History of seizures
At V05 (M8), for antibody persistence assessment (amendment 2)
18) Subjects who received, in the context of a pandemic immunization program,
another A/H1N1 pandemic influenza vaccine than the Investigational Medicinal
Products



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Preventive vaccination in healthy subjects aged 6 to 35 months against infection with S-OIV (Swine Origin Influenza Virus) A/California/7/2009 (H1N1)

Intervention(s)

Product Name: Swine A/H1N1 Influenza Vaccine (split virion, inactivated)
Product Code: 448
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Influenza virus (split virion, inactivated) A/California/7/2009 (NYMC X-179A) (H1N1)
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: not less then
Concentration number: 30-

Product Name: Swine A/H1N1 Influenza Vaccine (split virion, inactivated, adjuvanted with AF03)
Product Code: 452
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: Influenza virus (split virion, inactivated) A/California/7/2009 (NYMC X-179A) (H1N1)
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: not less then
Concentration number: 30-

Product Name: Swine A/H1N1 Influenza Vaccine (split virion, inactivated, adjuvanted with AF03)
Product Code: 452
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: Influenza virus (split virion, inactivated) A/California/7/2009 (NYMC X-179A) (H1N1)
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: not less then
Concentration number: 60-

Trade Name: VAXIGRIP
Product Name: Trivalent influenza vaccine (split virion, inactived), NH 2010-2011 formulation
Product Code: 314
Pharmaceutical Form: Suspension for injection
Other descriptive name: A/California/7/2009 (H1N1)-derived strain used NYMC X-179A
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: not less then
Concentration number: 30-
Other descriptive name: A/Perth/16/2009 (H3N2)-like strain used NYMC X-187 derived from A/Victoria/210/2009
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: not less then
Concentration number: 30-
Other descriptive name: B/Brisbane/60/2008
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: not less then
Concentration number: 30-

Primary Outcome(s)

Primary end point(s): A) Immunogenicity

* Primary Vaccination Series and Antibody Persistence (amendment 2)

HAI antibody (Ab) titers against the swine origin A/H1N1 strain measured with HAI method will be expressed as described below:
• HAI Ab titers will be obtained on D0, D21, and D42. The following endpoints will be derived:
• Individual titers ratios D21/D0, D42/D0, and D42/D21
• Subjects with HAI Ab titer =40 (1/dilution [dil]) on D0, D21, and D42
• Subjects with seroconversion or significant increase in HAI Ab titer, from D0 to D21 and from D0 to D42:
- Seroconversion for subjects with a pre-vaccination titer <10 (1/dil) on D0, post-vaccination titer =40 (1/dil)
or
- Significant increase for subjects with a pre-vaccination titer =10 (1/dil), =four-fold increase of the titer (post/pre)
• Subjects with detectable HAI Ab, i.e. with a titer =10 (1/dil), on D0, D21, and D42
HAI Ab titers will also be obtained at M8 for antibody persistence evaluation. The following endpoints will be derived: Subjects with HAI Ab titer =10 and=40 (1/dil) (amendment 2).
Following HAI testing neutralizing Ab titers will be measured with the seroneutralization (SN) method and expressed as described below:
• Neutralizing Ab titers will be obtained on D0, D21, and D42. The following endpoints will be derived:
• Individual titers ratios D21/D0, D42/D0, and D42/D21
• Two- and four-fold increase of titers from D0 to D21, D0 to D42, and D21 to D42
• Subjects with detectable neutralizing Abs, i.e. with a titer =10 (1/dil), on D0, D21, and D42
• Subjects with neutralizing Abs titer =20 and =40 (1/dil), on D0, D21, and D42

* Vaccination With the NH Seasonal TIV (amendment 3):

HAI Ab titers against the A/H1N1 influenza strain contained in the 2010-2011 NH seasonal TIV measured with the HAI method will be expressed as described below:
• HAI Ab titers will be obtained before (pre-TIV) and 21 days after last vaccination (post-TIV). The following endpoints will be derived:
• Individual titers ratios post-TIV/pre-TIV
• Subjects with HAI Ab titer =40 (1/dil) pre-TIV and post-TIV
• Subjects with seroconversion or significant increase in HAI Ab titer, from pre-TIV to post-TIV:
- Seroconversion for subjects with a pre-vaccination titer <10 (1/dil), post-vaccination titer =40 (1/dil)
or
- Significant increase for subjects with a pre-vaccination titer =10 (1/dil), =four-fold increase of the titer (post/pre)
• Subjects with detectable HAI Ab, i.e. with a titer =10 (1/dil), pre- and post TIV


B) Safety

• Occurrence of unsolicited adverse event (AE) reported in the 30 minutes after each/any injection (for primary series and TIV)
• Occurrence of solicited (prelisted in the subject diary and eCRF) injection site reactions and systemic reactions within 7 days following each/any injection (for primary series and TIV)
• Occurrence of unsolicited (spontaneously reported) AEs within 21 days following each/any injection (for primary series and TIV)
• Occurrence of the following reactions (Medical Dictionary for Regulatory Activities [MedDRA] Preferred Terms given in parentheses) in the 3 days following each injection in subjects =24 months (as defined for adults by the European Medicines Agency (EMEA) Note for Guidance [CPMP/BWP/214/96]):
• Injection site induration =5 cm for at least 4 consecutive days following each injection
• Injection site ecchymosis (injection site hemorrhage) in the 3 days following each injection
• Temperature >38°C (pyrexia) for 24 hours or more in the 3 days following each injection
• Malaise in the 3 days following each injection
• Shivering (chills) in the 3 days following each injection
• Occurrence of SAEs including adverse events of special interest (AESIs) within the 21 days following each/any vaccination (for primary series and TIV), and up to the end of the trial.
• Occurrence of biochemical or hematological test results of any grade and of biochemical or hematological test results clinically significant based on Investigator decision at pre-vaccination and 7 days after the first vaccination.

Main Objective: • To describe the immune response of each candidate vaccine 21 days after each vaccination by hemagglutination inhibition (HAI) and seroneutralization (SN)
testing in all subjects.
• To describe the antibody persistence eight months (M8) after the first vaccine administration using HAI method in a subset of subjects who received two half doses of either the 15 µg HA or 3.8 µg HA + AF03 vaccine (amendment 2).
• To describe the safety profiles (injection site reactions, and systemic events) of each candidate vaccine during the 21 days following each vaccination, and serious adverse events throughout the study in all subjects
•To describe the immune response against the A/H1N1 strain using the HAI method 21 days after last vaccination with the 2010-2011 NH seasonal TIV administered 13 months after the first vaccination in a subset of subjects who received two half-doses of either the 15 µg HA or 3.8 µg HA + AF03 A/H1N1 influenza vaccines as primary series (amendment 3).

Secondary Objective: Not applicable

Secondary ID(s)

GPF09