Safety and Immunogenicity of an Intramuscular H5N1 Inactivated, Split Virion Influenza Vaccine Adjuvanted with AF03 in Adults and Elderly subjects

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2010-019835-37-BE
• Date of registration: 17/05/2010
• Prospective Registration: Yes
• Primary sponsor: Sanofi Pasteur SA
• Public title: Safety and Immunogenicity of an Intramuscular H5N1 Inactivated, Split Virion Influenza Vaccine Adjuvanted with AF03 in Adults and Elderly subjects
• Scientific title: Safety and Immunogenicity of an Intramuscular H5N1 Inactivated, Split Virion Influenza Vaccine Adjuvanted with AF03 in Adults and Elderly subjects
• Date of first enrolment: 29/06/2010
• Target sample size: 3200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019835-37
• 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

Belgium, France, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
An individual must fulfill all of the following criteria in order to be eligible for trial enrollment:
1) Aged 18 years or over on the day of inclusion
2) Informed Consent Form has been signed and dated
3) Able to attend all scheduled visits and to comply with all trial procedures
4) For a woman, use of an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination, or having undergone a surgical sterilization or being post-menopausal
5) Covered by health insurance or entitled to national social security depending on local regulations
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
An individual fulfilling any of the following criteria is to be excluded from trial enrollment:
1) Known pregnancy, or a positive urine pregnancy test
2) Currently breastfeeding a child
3) Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial vaccination
4) Planned participation in another clinical trial during the present trial period
5) Receipt of any vaccine in the 4 weeks preceding the first trial vaccination
6) Planned receipt of any vaccine prior to the blood sample performed 21 days after the second trial vaccination
7) Previous vaccination with an H5N1 vaccine
8) History of H5N1 infection or exposure to presumed/confirmed (either clinically, serologically, or microbiologically) cases of H5N1-infected humans or animals
9) Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response
10) 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)
11) Self-reported seropositivity for Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C
12) 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
13) Self-reported thrombocytopenia, contraindicating IM vaccination
14) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination in the opinion of the investigator
15) Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
16) Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures
17) Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
18) Identified as employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employees or the Investigator.
19) Febrile illness (temperature =38.0°C) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination
20) Receipt of any vaccine with an adjuvant (except for aluminum) in a context of a clinical trial in the past 2 years
21) Receipt of an A/H1N1 pandemic influenza vaccine in the context of the national pandemic vaccination campaign 2009-2010
22) Known or suspected autoimmune disease or systemic disease (e.g. Sjögren syndrome, lupus erythematosus, rhumatoïde arthritis, sarcoïdosis, vasculitis, etc…)


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

Health Condition(s) or Problem(s) studied

Preventive vaccination study in healthy subjects aged 18-60 years and over 60 years against infection with H5N1 Influenza Virus A/Indonesia/5/05-RG2 (H5N1)

Intervention(s)

Product Name: Pandemic Flu Vaccine (H5N1) (split virion, inactived, adjuvanted with AF03)
Product Code: 414
Pharmaceutical Form: Emulsion for injection
Other descriptive name: Inactived split influenza virus A/Indonesia/5/05-RG2 (H5N1)
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: not less then
Concentration number: 30-

Product Name: Pandemic Flu Vaccine (H5N1) (split virion, inactived)
Product Code: 364
Pharmaceutical Form: Suspension for injection
Other descriptive name: Inactived split influenza virus A/Indonesia/5/05-RG2 (H5N1)
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: not less then
Concentration number: 30-

Primary Outcome(s)

Secondary Objective: Not applicable

Primary end point(s): Safety
• Occurrence of unsolicited adverse event (AE) reported in the 30 minutes after each/any injection
• Occurrence of solicited (prelisted in the subject diary and electronic Case Report Form [eCRF]) injection site reactions and systemic reactions within 7 days following each/any injection
• Occurrence of unsolicited (spontaneously reported) AEs within 21 days following each/any injection in subjects vaccinated following the D0-D21 or D0-D42 schedules or, 14 days and 21 days after the first and second injection respectively, in subjects vaccinated following the D0-D14 schedule
• Occurrence of the following solicited reactions (Medical Dictionary for Regulatory Activities [MedDRA] Preferred Terms given in parentheses) in the 3 days following each injection will be more specifically reported (as defined 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 serious AEs (SAEs) including adverse events of special interest (AESI) throughout the trial
Other endpoints recorded or derived will be described at the time of statistical analysis plan. Depending on the item, these could include: nature (MedDRA preferred term), time of onset, duration, number of days of occurrence, Grade of severity, relationship to vaccine, action taken, whether the AE led to early termination from the study, seriousness, or outcome.
Note: The following AESIs, considered as important medical events are to be considered as SAEs and reported to the Sponsor: anaphylaxis, Guillain-Barré syndrome (GBS), encephalitis, Bell’s palsy, neuritis, convulsions, vasculitis, demyelinating disorders and any suspected/confirmed autoimmune disease including Sjögren Syndrome.


Immunogenicity
Anti-HA Ab titers against the H5N1 strain will be measured using hemagglutination inhibition (HAI) assay using horse erythrocytes (HIH) and seroneutralization (SN) methods. Anti-HA Ab titers will be expressed as described below:

=> Primary Series:
• HAI and SN Ab titers will be obtained on D0 and D21 on a randomized subset of subjects vaccinated following the D0-D21 schedule. The following endpoints will be derived:
• Individual titers ratio D21/D0, D42/D0 and D42/D21 (HAI and SN)
• Subjects with titer =40 (1/dilution [dil]) on D0, D21 and D42 (HAI and SN).
• Subjects with seroconversion or significant increase in HAI Ab titer, from D0 to D21 or D0 to D42 (HAI):
- 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 Ab, i.e. with a titer =10 (1/dil) (HAI and SN), =20 and =80 (1/dil) (SN only) on D0, D21 and D42
• Percentage of subjects achieving a 2 and 4-fold increase of titers (SN only) from D0 to D21 and D0 to D42

=> Ab Persistence:
• HAI Ab titers will be obtained at Vac2+6M and Vac2+12M on a randomized subset of subjects. The following endpoints will be derived:
• Subjects with detectable Ab, i.e. with a titer =10 (1/dil) (HAI and SN), =20, =40 and =80 (1/dil) (SN only) at Vac2+6M and Vac2+12M
• Subjects with HAI Ab titer =40 (1/dil) at Vac2+6M and Vac2+12M

Main Objective: • To describe the safety profile of the vaccines (injection site reactions and systemic events) either 21 days after each injection in subjects vaccinated following the D0-D21 or D0-D42 schedules or, 14 days and 21 days after the first and second injection respectively, in subjects vaccinated following the D0-D14 schedule

• To describe the immunogenicity 21 days after each vaccine injection in a randomized subset of subjects vaccinated following the D0-D21 schedule and participating to immunogenicity evaluation

• To describe the persistence of antibodies (Ab) 6 and 12 months after the second vaccine injection in the randomized subset of subjects vaccinated following the D0-D21 schedule and participating to immunogenicity evaluation.

Secondary ID(s)

GPF15