Immunogenicity and Tolerability Study of Fluval AB Novo Suspension for Injection for Children and Adolescents

STUDY PERIOD:

Length of enrollment: 2 weeks (estimated) Participation per subject: max. 1 month

OBJECTIVES:

Immunogenicity Objectives:

To assess immunogenicity of a single intramuscular injection of Fluval AB Novo suspension for injection (trivalent, seasonal influenza vaccine, active ingredient content: 6 μg HA/0.5 ml of seasonal A/H1N1, A/H3N2 and B influenza antigens each), as measured by haemagglutination inhibition (HI) test.

Safety and Tolerability Objectives:

To evaluate safety and tolerability (incidence of adverse events) of a single intramuscular injection of Fluval AB Novo suspension for injection.

CLINICAL PHASE:

Phase III

TYPE:

Interventional, prevention

DESIGN:

Non-controlled, open, multi-centre

METHODS:

In this uncontrolled, open, multi-centre immunogenicity and tolerability study subjects were enrolled into two groups according to age:

Age group 1: children (3-11 years): single intramuscular injection of Fluval AB Novo 0.25 ml suspension for injection; Age group 2: adolescents (12-18 years): single intramuscular injection of Fluval AB Novo 0.5 ml suspension for injection; Subjects were observed for 30 minutes after the injection for any immediate reactions.

All adolescent subjects aged 12 to 18 years and the legitimate representatives of all volunteers were requested to complete a Diary Card (DC) to record local reactions (injection site pain, erythema, swelling, induration, numbness, sensitivity and haematoma) and systemic reactions (fever, shivering, headache, malaise, fatigue, sweating, nausea, myalgia, arthralgia, dizziness and urticaria) starting on the day of vaccination on Visit 1 (Day 0) until 7 days following that.

All adverse events were collected during the period of Visit 1 (Day 0) to Visit 2 (between Day 21 and Day 28); Serum samples for immunogenicity assays were collected immediately before immunization on Visit 1 (Day 0) and on Visit 2 (between Day 21 and Day 28) in all subjects. Immunogenicity were evaluated by HI test.

INVESTIGATIONAL MEDICINAL PRODUCT:

Fluval AB Novo suspension for injection (trivalent, seasonal influenza vaccine, active ingredient content: 6 μg HA/0.5 ml of seasonal A/H1N1, A/H3N2 and B influenza antigens each) with aluminium phosphate gel adjuvant.

Lot No.: FL-N-05/13

CONCOMITANT VACCINES:

No concomitant vaccination is permitted for the duration of the study except for post-exposure vaccination in a medical emergency (e.g. tetanus, rabies, hepatitis).

STUDY POPULATION:

Considering approximately 17% of drop-out (one participant out of six), in total 120 subjects (60 subjects in each age group) were enrolled in order to achieve at least 100 evaluable subjects (50 subjects in each age group).

Inclusion criteria

• Children aged 3 to 11 years, adolescents aged 12 to 18 years from both sexes;
• Are in good health (as determined by vital signs and existing medical condition) or are in stable medical condition. Subjects will not be excluded with known adequately treated clinically significant organ or systemic diseases (e.g. asthma or diabetes), such that, in the opinion of the investigator, the significance of the disease will not compromise the subject's participation in the study;
• Female volunteers of childbearing potential with a negative result from the urine pregnancy test prior to vaccination who agrees to use an acceptable contraception method or abstinence throughout the trial and not become pregnant for the duration of the study;
• Capability of adolescent participants aged 12 to 18 years and the legitimate representative of all volunteers to understand and comply with planned study procedures;
• Adolescent participants aged 12 to 18 years and the legitimate representative of all volunteers provide written Informed Consent (IC) prior to initiation of study procedures;
• Absence of existence of any exclusion criteria.

Exclusion criteria

• Pregnancy, breast feeding or positive urine pregnancy test at baseline prior to vaccination. Female subjects who are able to bear children but not willing to use an acceptable contraception method for the duration of the study.
• Known hypersensitivity to eggs, thiomersal, formaldehyde, gentamycin, ciprofloxacin, neomycin, vancomycin or any other component of the vaccine;
• History of Guillain-Barré syndrome;
• History of neurological symptoms or signs, or anaphylactic shock following administration of any vaccine;
• Serious disease, such as cancer, autoimmune disease, advanced arteriosclerotic disease, complicated diabetes mellitus, acute or progressive hepatic disease, acute or progressive renal disease, congestive heart failure;
• Immunosuppressive therapy within 36 months prior to vaccination;
• Concomitant corticosteroid therapy, including high-dose inhaled corticosteroids;
• Receipt of immunostimulants,
• Receipt of parenteral immunoglobulin, blood products and/or plasma derivate within 3 months prior to vaccination;
• Suspected or known HIV, HBV or HCV infection;
• Acute disease and/or axillary temperature ≥37oC within 3 days prior to vaccination;
• Vaccine therapy within 4 weeks prior to vaccination;
• Influenza vaccination (any kind) within 6 months prior to vaccination;
• Experimental drug therapy within 4 weeks prior to vaccination;
• Concomitant participation in another clinical study;
• Any condition which, in the opinion of the investigator, may interfere with the evaluation of the study;
• Past or current psychiatric disease of the volunteer or the legitimate representative that upon judgement of the investigator may have effect on the objective decision-making of the volunteer;
• Alcohol or drug abuse of the participant or the legitimate representative.