Safety and Immunogenicity of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine (GSK-580299) in Healthy Female Children 4-6 Years Old

GlaxoSmithKline148 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Enrollment

148

Conditions

Infections, Papillomavirus

Interventions

CervarixBIOLOGICAL

2 doses administered intramuscularly in the deltoid muscle of the left arm at Day 0 and Month 6.

PriorixBIOLOGICAL

1 dose administered intramuscularly in the deltoid muscle of the left arm at Day 0.

InfanrixBIOLOGICAL

1 dose administered intramuscularly in the deltoid muscle of the left arm at Month 6.

Eligibility

Sex: FEMALEMin age: 4 YearsMax age: 6 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.)

Locations (4)

GSK Investigational Site

Bogotá, Colombia

GSK Investigational Site

Yopal, Casanare, Colombia

GSK Investigational Site

México, Mexico

GSK Investigational Site

Panama City, Panama

Outcomes

Primary Outcomes

Number of Subjects With Any and Grade 3 Solicited Local Symptoms

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.

Time frame: During the 7-day follow-up period (i.e. from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses

Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

Assessed solicited general symptoms were arthralgia (only in joints which were distal from the injection site), drowsiness, fatigue, fever \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, irritability/fussiness, loss of appetite, myalgia, rash (not urticaria, not measels/rubella-like rash), urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Grade 3 irritability/fussiness = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = did not eat at all. Related = symptom assessed by the investigator as causally related to the study vaccination.

Time frame: During the 7-day follow-up period (i.e. from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses

Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) Reported During the 43-day Period Following the Vaccination at Day 0

An unsolicited AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related AE = AE assessed by the investigator as causally related to the study vaccination.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Number of Seroconverted Subjects for HPV-16 and HPV-18 Antigens at Month 7, Month 12 (for Both Groups) and at Month 18, Month 24 and Month 36 (Only for Cervarix Group)

Seroconversion was defined as a titer greater than or equal to the cut-off value in the serum of seronegative subjects, defined as subjects who had an antibody titer below the cut-off value before vaccination. Titers were measured by ELISA and the cut-offs were 19 EU/mL for HPV-16 and 18 EU/mL for HPV-18. Note: Month 7 data are also reported in the Primary outcome measure.

Time frame: At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group)

Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations at Month 7, Month 12 (for Both Groups) and at Month 18, Month 24 and Month 36 (Only for Cervarix Group)

Antibody concentrations were assessed by ELISA and expressed as GMCs in EU/mL. Note: Month 7 data are also reported in the Primary outcome measure.

Time frame: At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group)

Number of Seropositive Subjects for Measles Antigen

A seropositive subject was defined as a subject whose anti-measles antibody titer was equal to or above (≥) 150 milli-International Units per milliliter (mIU/mL), as assessed by ELISA.