Safety and Immunogenicity of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine (GSK-580299) in Healthy Female Children 4-6 Years Old
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 148
- 试验地点
- 4
- 主要终点
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 4 Years 至 6 Years（Child）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.)
结局指标
主要结局
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
时间窗: 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
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.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
时间窗: 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
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.
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
时间窗: During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) 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.
Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters at Month 7 by Baseline Ranges
时间窗: At Month 7 (i.e. 30 days after the vaccination at Month 6)
The parameters assessed were both biochemical (alanine aminotransferase = ALAT, creatinine = CREA, blood urea nitrogen = BUN) and haematological (basophils = BAS, eosinophils = EOS, red blood cells = RBC, hematocrit = HCT, hemoglobin = HGB, leukocytes \[white blood cells\] = WBC, lymphocytes = LYM, monocytes = MONO, neutrophils = NEU and platelets = PLA). Abnormal laboratory values at Month 7 were Below, Within and Above normal ranges, as compared to the baseline status of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) \[e.g. ALAT Below (baseline) - Within (Month 7) = ALAT with below normal value at baseline and within normal values at Month 7\].
Number of Subjects With Serious Adverse Events (SAEs) From Day 0 up to Month 7
时间窗: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
SAEs assessed included medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
Number of Subjects With AEs and SAEs Leading to Withdrawal From Day 0 up to Month 7
时间窗: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
The number of subjects with AEs and SAEs leading to premature discontinuation of the study was assessed.
Number of Seroconverted Subjects for HPV-16 and HPV-18 Antigens at Month 7
时间窗: At Month 7 (i.e. 30 days after the vaccination at Month 6)
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 Enzyme Linked Immunosorbent Assay (ELISA) and the cut-offs were 19 ELISA Units per milliliter (EU/mL) for HPV-16 and 18 EU/mL for HPV-18.
Anti-HPV-16/18 Antibody Concentrations at Month 7
时间窗: At Month 7 (i.e. 30 days after the vaccination at Month 6)
Antibody concentrations were assessed by ELISA and expressed as geometric mean concentrations (GMCs) in EU/mL.
Number of Subjects With Any, Grade 3 and Related Unsolicited AEs Reported During the 30-day Period Following the Vaccination at Month 6
时间窗: During the 30-day period (i.e. from the day of vaccination up to 29 subsequent days) following the vaccination at Month 6
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.
Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters at Day 42 by Baseline Ranges
时间窗: At Day 42 (i.e. 42 days after the vaccination at Day 0)
The parameters assessed were both biochemical (alanine aminotransferase = ALAT, creatinine = CREA, blood urea nitrogen = BUN) and haematological (basophils = BAS, eosinophils = EOS, red blood cells = RBC, hematocrit = HCT, hemoglobin = HGB, leukocytes \[white blood cells\] = WBC, lymphocytes = LYM, monocytes = MONO, neutrophils = NEU and platelets = PLA). Abnormal laboratory values at Day 42 were Below, Within and Above normal ranges, as compared to the baseline status of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) \[e.g. ALAT Below (baseline) - Within (Day 42) = ALAT with below normal value at baseline and within normal values at Day 42\].
Number of Subjects With Potential Immune-mediated Diseases (pIMDs) From Day 0 up to Month 7
时间窗: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
pIMDs were defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which might or might not have an autoimmune aetiology.
Number of Subjects With Medically Significant Conditions (MSCs) From Day 0 up to Month 7
时间窗: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
MSCs were defined as AEs prompting emergency room or physician visits that were not related to common diseases or were not routine visits for physical examination or vaccination and as SAEs that were not related to common diseases. Common diseases included: upper respiratory tract infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections and injury.
次要结局
- Anti-mumps Antibody Concentrations(At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0))
- Number of Seropositive Subjects for Measles Antigen(At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0))
- Anti-measles Antibody Concentrations(At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0))
- Number of Seropositive Subjects for Rubella Antigen(At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0))
- Anti-rubella Antibody Concentrations(At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0))
- Number of Subjects With pIMDs From Day 0 up to Month 12(From Day 0 up to Month 12 (i.e. from first vaccination at Day 0 up to 6 months after the second vaccination at Month 6))
- Number of Subjects Reporting the Intake of Concomitant Medication During the 30-day Period Following the Vaccination at Month 6(During the 30-day period (i.e. from the day of vaccination up to 29 subsequent days) following the vaccination at Month 6)
- Number of Seropositive Subjects for Mumps Antigen(At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0))
- Number of Subjects With MSCs From Day 0 up to Month 12(From Day 0 up to Month 12 (i.e. from first vaccination at Day 0 up to 6 months after the second vaccination at Month 6))
- 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)(At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group))
- Number of Subjects With SAEs From Day 0 up to Month 12(From Day 0 up to Month 12 (i.e. from first vaccination at Day 0 up to 6 months after the second vaccination at Month 6))
- 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)(At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group))
- Percentage of Subjects Completing the Vaccination Schedule in Both Groups(From Day 0 up to Month 6 (i.e. from first vaccination at Day 0 up to the second vaccination at Month 6))
- Number of Seroprotected Subjects Against Diphtheria and Tetanus Antigens(At Month 7 (i.e. 30 days after the vaccination at Month 6))
- Number of Subjects With SAEs Related to the Investigational Products or Any Fatal SAE(Throughout the study period (i.e. from Day 0 up to Month 12 for Priorix + Infanrix Group and from Day 0 up to Month 36 for Cervarix Group))
- Number of Subjects With AEs/SAEs Leading to Withdrawal Throughout the Study Period(Throughout the study period (i.e from Day 0 up to Month 12 for Priorix + Infanrix Group and from Day 0 up to Month 36 for Cervarix Group))
- Number of Subjects Reporting the Intake of Concomitant Medication During the 43-day Period Following the Vaccination at Day 0(During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0)
- Number of Subjects With Any, Grade 3 and Related to Vaccination Solicited Fever, Measles/Rubella-like Rash, Parotid Gland Swelling and Signs of Meningism Including Febrile Convulsion(During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0)