Safety and Immunogenicity of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine (GSK-580299) in Healthy Female Children 4-6 Years Old
Condition: Infections, Papillomavirus
Intervention: Cervarix; Priorix; Infanrix
Intervention description: 2 doses administered intramuscularly in the deltoid muscle of the left arm at Day 0 and Month 6.; 1 dose administered intramuscularly in the deltoid muscle of the left arm at Day 0.; 1 dose administered intramuscularly in the deltoid muscle of the left arm at Month 6.
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 148.0
Sex: Female
Minimum age: 4 Years
Maximum age: 6 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Immune response; Human papillomavirus; HPV vaccine; Safety

Summary:

      The current study evaluates the immunogenicity and safety in 4-6 years old female subjects
      (experimental group) receiving Cervarix according to a 2-dose schedule (Month 0, 6), as
      compared to 4-6 years old female subjects (control group) receiving sequentially Priorix
      (Month 0) and Infanrix (Month 6) vaccines.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects who the investigator believes that parent(s)/Legally Acceptable
             Representative(s) [LAR(s)] can and will comply with the requirements of the protocol.

          -  A female between, and including, 4 and 6 years of age at the time of the first
             vaccination.

          -  Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to
             enrolment in the study.

          -  Healthy subjects as established by medical history and clinical examination before
             entering into the study.

          -  Subjects who received four doses of DTP vaccine (i.e., three doses in the first year
             of life and a fourth dose in the second year of life) according to the schedule
             applicable in the participating countries.

          -  Subjects who received a first dose of MMR vaccine according to the schedule applicable
             in the participating countries.

        Exclusion Criteria:

          -  Child in care.

          -  Previous vaccination against HPV or planned administration of another HPV vaccine
             during the study other than that foreseen in the protocol.

          -  Planned administration/administration of a vaccine not foreseen by the study protocol
             within 30 days before the first dose of study vaccine(s). Administration of routine
             meningococcal, hepatitis B, hepatitis A, inactivated influenza and/or poliomyelitis
             vaccines up to 8 days before the first dose of study vaccine(s) is allowed. Enrolment
             will be deferred until the subject is outside of specified window.

          -  Use of any investigational or non-registered product (drug or vaccine) other than the
             study vaccines within 30 days preceding the first dose of study vaccine(s), or planned
             use during the study period.

          -  History of any reactions or hypersensitivity likely to be exacerbated by any component
             of the study vaccines, including latex and/or obvious allergic reactions to neomycin
             (a history of contact dermatitis to neomycin is not a contraindication), egg protein,
             etc. (e.g. hives, swelling of the mouth and throat, difficulty breathing, hypotension,
             or shock subsequent to egg ingestion).

          -  Cancer or autoimmune disease under treatment.

          -  Concurrently participating in another clinical study, at any time during the study
             period, in which the subject has been or will be exposed to an investigational or a
             non-investigational product (pharmaceutical product or device).

          -  Previous administration of MPL or AS04 adjuvant.

          -  Administration of immunoglobulins and/or any blood products within the three months
             preceding the first dose of study vaccine(s) or planned administration during the
             study period.

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
             medical history and physical examination (no laboratory testing required).

          -  Family history of congenital or hereditary immunodeficiency.

          -  Documented human immunodeficiency virus (HIV)-positive subject.

          -  Major congenital defects or serious chronic illness.

          -  History of seizures or serious neurological disorder, which, according to the judgment
             of the investigator, precludes administration of any of the study vaccines.

          -  Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal
             functional abnormality, as determined by physical examination or laboratory screening
             tests, which in the opinion of the investigator precludes administration of the study
             vaccine(s).

          -  Acute disease and/or fever at the time of enrolment.

               -  Fever is defined as temperature ≥ 37.5°C on oral, axillary or tympanic setting,
                  or ≥ 38.0°C on rectal setting.

               -  Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory
                  infection) without fever may, be enrolled at the discretion of the investigator.
                  Enrolment can be deferred until condition is resolved.

          -  Previous administration of the fifth dose of DTP vaccine and/or the second dose of MMR
             vaccine or planned administration of DTP vaccine and/or MMR vaccine outside the study
             (during the study period from Day 0 to Month 12).

          -  History of tetanus, diphtheria, pertussis, measles, mumps and/or rubella.

          -  Known exposure to diphtheria or household exposure to pertussis within 30 days prior
             to vaccination with DTPa.

          -  Known exposure to measles, mumps and/or rubella 30 days prior to vaccination with the
             MMR study vaccine.

          -  Confirmed or suspected tuberculosis.

          -  Severe allergic reactions (e.g. anaphylaxis or severe Arthus-type hypersensitivity
             reactions) following the administration of previous dose(s) of DTP or MMR vaccines.

          -  Hyperpyrexia (≥ 40.5°C) within 48 hours of administration of previous doses of DTP or
             MMR vaccines.

          -  Persistent, inconsolable crying lasting more than 3 hours, occurring within 48 hours
             of administration of previous doses of DTP vaccine.

          -  Collapse or shocking-like state (hypotonic-hyporesponsive episode) within 48 hours of
             administration of previous doses of DTP vaccine.

          -  Idiopathic thrombocytopenic purpura or bleeding disorders.

          -  Chronic administration (defined as more than 14 days in total) of immunosuppressants
             or other immune-modifying drugs within six months prior to the first vaccine dose(s).
             (For corticosteroids, this will mean prednisone ≥ 0.5 mg/kg/day, or equivalent.
             Inhaled and topical steroids are allowed.)