A Parallel-controlled Study to Evaluate the Immunogenicity and Safety of Recombinant Nonavalent (Types 6/11/16/18/31/33/45/52/58) Human Papillomavirus (HPV) Vaccine (Escherichia Coli) in Healthy Female Participants Aged 9-26 Years in China
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 2,750
- 试验地点
- 1
- 主要终点
- Seroconversion Rate (SCR) of anti-HPV type 6/11/16/18/31/33/45/52/58 neutralizing antibodies for study vaccine group
研究概览
简要总结
The study is to evaluate immune response induced by 9-valent HPV study vaccine is non-inferior to those induced by GARDASIL® 9 administrated with 3-dose schedule in female participants aged 20-26 years in China, if the immune response induced with same conditions in 9-19 age group is non-inferior to 20-26 age group, and if the immune response induced by 9-valent HPV study vaccine administrated with 2-dose schedule in females aged 9-14 years is non-inferior to 3-dose schedule in females aged 20-26 years.
详细描述
This is a parallel-controlled study. A total of 2,750 participants will be enrolled in this study: 9-14 years (2 doses) group and 9-19 years (3 doses) group are of non-randomized, open label design; 20-26 years (3 doses) group will be randomized and blinded.
9-14 age group and group 9-19 age group will be enrolled in two stages: 20 subjects in 9-19 age group will be enrolled first. After assessing the safety data (including laboratory test data) within 7 days of 1st dose vaccination in these 20 subjects, and if the suspension criteria are not met, the remaining 620 subjects in 9-19 age group and 640 subjects in 9-14 age group will be enrolled subsequently. 20-26 age group will be enrolled directly, with no stage entry requirements. Eligible subjects will be enrolled to received vaccines accordingly. Subjects who have reached menarche will undergo urine pregnancy test prior to each dose of vaccination (on the vaccine day.)
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
- Double (Participant, Investigator)
盲法说明
The Sponsor, investigators and biostatisticians will remain blinded to subject allocation.
入排标准
- 年龄范围
- 9 Years 至 26 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •* Fever (axillary temperature ≥ 37.3°C in participants >14 years and ≥ 37.5°C in participants ≤14 years) within 24 hours prior to the 1st dose of vaccination.
- •Previously vaccinated or have plans to administer other HPV vaccines during the study period.
- •Plans to participate in other clinical studies during the study period or participate in other unfinished clinical trials within three months before participating in this clinical study; have used or plan to use other investigational or unregistered products (drugs or vaccines) within 28 days prior to 1st vaccination of this study vaccine.
- •History of HPV positive, history of cervical lesions (e.g., abnormal cervical cancer screening results, history of abnormal cervical biopsy results, including cervical intraepithelial neoplasia (CIN), cervical low grade squamous intraepithelial lesions (LSIL), adenocarcinoma in situ or cervical cancer), history of HPV infection or abnormal cytology test or history of pelvic radiation therapy.
- •History of anogenital disease associated with HPV infection (e.g., genital warts, vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), anal intraepithelial neoplasia and associated carcinoma, etc.); or history of STDs (including syphilis, gonorrhea, genital chlamydia, genital herpes, soft chancre, lymphogranuloma venereum, inguinal sarcoidosis, etc.).
- •Abnormalities of grade 1 or higher in the laboratory tests specified in this protocol, confirmed by clinician to be clinically significant (only applicable to the 20 subjects enrolled first in group B during the 1st stage).
- •Allergy to any component of the study vaccine (including aluminum hydroxide adjuvant, sodium chloride, histidine, polysorbate, etc.) or previous serious adverse events to vaccination; previous history of serious allergy, including anaphylaxis, allergic laryngeal edema, allergic purpura, thrombocytopenic purpura, local allergic necrotizing reaction (Arthus reaction), severe urticaria, respiratory distress, angio neuroedema, etc.
- •Participants with an impaired immune system or who have been diagnosed with an innate or acquired immune deficiency such as HIV infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune disease.
- •Epilepsy, excluding febrile convulsions under 2 years of age, or alcoholic epilepsy 3 years prior to abstinence from alcohol, or simple epilepsy not requiring treatment in the past 3 years.
- •Current severe liver or kidney disease, serious cardiovascular disease, diabetes, malignancy, serious infectious disease (e.g., tuberculosis, HIV infection, etc.)
- •Untreated/uncontrolled hypertension (systolic blood pressure > 120 mmHg and/or diastolic blood pressure > 80 mmHg) prior to vaccination for age 9-17 years; untreated/uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg) prior to vaccination for age 18 years and older.
- •Physician-diagnosed coagulation abnormalities (e.g., coagulation factor deficiency, coagulopathies, platelet abnormalities) or clotting disorders
- •Absence of spleen, asplenia, and any condition resulting asplenia or splenectomy.
- •Participant has received immunosuppressive therapy within 1 month prior to vaccination or is scheduled to receive such therapy during the visit from the 1st dose to 30 days after full vaccination; e.g., long-term systemic glucocorticoid therapy (≥2 mg/kg/day for 2 weeks or more, e.g., prednisone or equivalent); topical medications (e.g., ointments, eye drops, inhalers, or nasal sprays) are allowed.
- •Have received immunoglobulin products or blood-related products within 3 months prior to the 1st dose, or plan to use such products during visits between the 1st dose and 30 days after full vaccination.
- •* Acute illness or in acute exacerbation of chronic disease or use of antipyretic, analgesic and antiallergic medications (e.g., acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.) within 3 days prior to vaccination.
- •* Administration of inactivated/recombinant/nucleic acid vaccines, etc. (non-attenuated vaccines) within 14 days prior to study entry or attenuated vaccines within 28 days prior to study enrollment.
- •* Participant has donated blood within 1 week prior to enrollment or plans to donate blood during the period of 1st dose vaccination to 30 days after full vaccination.
- •A history of psychiatric disorders or current psychiatric disorders result in the inability to comply with study requirements
- •Based on the judgement of investigator, due to various medical, psychological, social, occupational factors or other conditions that are contrary to the study protocol or could affect the signing of ICF by the subject and/or guardian (trustee).
- •Criteria for delay of the subsequent doses of vaccination:
- •Participants with confirmed pregnancy prior to vaccination (on the day of vaccination), should delay vaccination to 6 weeks after termination of pregnancy in addition to having a negative urine pregnancy test.
- •Vaccination may be delayed after evaluation by the investigator:
- •On the day of vaccination, axillary temperature ≥ 37.3°C measured in participants aged > 14 years; axillary temperature ≥ 37.5°C measured in participants aged ≤ 14 years.
- •Treated with immunomodulators, immunoglobulins, or blood-related products in an interval of less than 3 months with vaccination day.
- •Acute illness or acute exacerbation of a chronic disease or use of antipyretic, analgesic and anti-allergic drugs (e.g., acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.) 3 days prior to vaccination.
- •Inadequate interval with other vaccinations (receipt of inactivated/recombinant/nucleic acid vaccine, etc. (non-attenuated vaccine) within 14 days or within 28 days for attenuated vaccine before vaccination).
- •The presence of other conditions that the investigator considers to warrant a delay in vaccination.
结局指标
主要结局
Seroconversion Rate (SCR) of anti-HPV type 6/11/16/18/31/33/45/52/58 neutralizing antibodies for study vaccine group
时间窗: 30 days after full immunization
Seroconversion Rate (SCR) of anti-HPV type 6/11/16/18/31/33/45/52/58 neutralizing antibodies (pseudo-virus neutralizing assay) 30 days after full vaccination, for participants in study vaccine group: aged 9-14 years (2 doses) group, aged 9-19 years (3 doses) group and aged 20-26 years (3 doses) group
Geometric mean titer (GMT) of anti-HPV type 6/11/16/18/31/33/45/52/58 neutralizing antibodies for study vaccine group
时间窗: 30 days after full immunization
Geometric mean titer (GMT) of anti-HPV type 6/11/16/18/31/33/45/52/58 neutralizing antibodies (pseudo-virus neutralizing assay) 30 days after full vaccination, for participants in study vaccine group: aged 9-14 years (2 doses) group, aged 9-19 years (3 doses) group and aged 20-26 years (3 doses) group.
次要结局
- GMT of anti-HPV type 6/11/16/18/31/33/45/52/58 neutralizing antibodies after first vaccination(From the 12th month to 72nd month after first dose immunization)
- Collect the questionnaires to gather the information related to the Incidence, intensity, and duration of solicited (local and systemic) AEs which within 7 days after each dose(0-7 days after each dose)
- Collect the questionnaires to gather the information related to the Incidence, intensity, and duration of SAE(Through study completion, an average of 6 years)
- GMT of anti-HPV 6/11/16/18/31/33/45/52/58 specific IgG antibodies for all subjects(30 days after full immunization)
- Collect the questionnaires to gather the information related to the Incidence, intensity, and duration of the occurrence of pregnancy events(Through study completion, an average of 6 years)
- Geometric mean titer (GMT) of anti-HPV type 6/11/16/18/31/33/45/52/58 neutralizing antibodies for study vaccine group and possitive control group(30 days after full immunization)
- Abnormality rate of laboratory test(Day 3 after each dose)
- SCR of anti-HPV 6/11/16/18/31/33/45/52/58 specific IgG antibodies for all subjects(30 days after full immunization)
- SCR of anti-HPV type 6/11/16/18/31/33/45/52/58 neutralizing antibodies after first vaccination(From the 12th month to 72nd month after first dose immunization)
- Follow up 30 minutes observation after injection to collect the Incidence, intensity, and duration of AEs(30 minutes after each dose)
- Seroconversion Rate (SCR) of anti-HPV type 6/11/16/18/31/33/45/52/58 neutralizing antibodies for study vaccine group and possitive control group(30 days after full immunization)
- Collect the questionnaires to gather the information related to Incidence, intensity, and duration of unsolicited AEs which within 30 days after each dose(0-30 days after each dose)