A Phase 4, Placebo-Controlled, Randomized Study to Evaluate the Immunogenicity and Safety of a Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine (Tdap, Boostrix®) and Quadrivalent Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine (Gardasil®) in Healthy Adolescents When Administered With MenACWY Conjugate Vaccine
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 801
- 试验地点
- 40
- 主要终点
- Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo
研究概览
简要总结
The main objective is to determine whether immune responses to Tdap (GlaxoSmithKline, Boostrix®) and HPV vaccine (Merck & Co., Inc., Gardasil®) when administered concomitantly with MenACWY are comparable to responses elicited by these vaccines when given alone.
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)
入排标准
- 年龄范围
- 11 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Individuals eligible for enrollment in this study were female and male individuals who had been shown to be healthy and who were:
- •11-18 years of age inclusive who had given their written consent/assent and if applicable, whose parents or legal guardians had given written informed consent at the time of enrollment;
- •Available for all visits and telephone calls scheduled for the study;
- •In good health as determined by:
- •Medical history
- •Physical assessment
- •Clinical judgment of the investigator
- •Had been properly vaccinated against diphtheria, tetanus, and pertussis per local regulations;
- •Subjects who were current with childhood DTP-containing vaccinations per local guidelines. Any previous vaccinations containing DTP must have been received at least 5 years before study enrollment and no prior adolescent vaccinations (11-18 years of age) containing DTP vaccines were allowed.
- •For female subjects, who had a negative urine pregnancy test.
- •Any female subject who is sexually active committed to practice appropriate birth control.
排除标准
- •Individuals not eligible to be enrolled in the study were those:
- •Who were unwilling to give their written assent / consent
- •Who were breastfeeding
- •Who was, and/or whose parents or legal guardians were perceived to be unreliable or unavailable for the duration of the study period
- •Who had previous confirmed or suspected disease caused by N. meningitidis
- •Who had household contact with and/or intimate exposure to an individual with culture-proven N. meningitidis infection within 60 days prior to enrollment
- •Who had previously been immunized with a meningococcal vaccine or vaccine containing meningococcal antigen(s) (licensed or investigational). (Exception: Receipt of OMP-containing Hib vaccines was permitted)
- •Who had received prior human papillomavirus (HPV) vaccine
- •Who had received investigational agents or vaccines within 30 days prior to enrollment or who expected to receive an investigational agent or vaccine prior to completion of the study
- •Who had received live licensed vaccines within 30 days and inactive vaccine within 15 days prior to enrollment or for whom receipt of a licensed vaccine is anticipated during the study period.
- •(Exception: Influenza vaccine could be administered up to 15 days prior to each study immunization and no less than 15 days after each study vaccination)
- •Who had experienced, within the 7 days prior to enrollment, significant acute or chronic infection (for example requiring systemic antibiotic treatment or antiviral therapy) or had experienced fever (defined as body temperature ≥ 38°C) within 3 days prior to enrollment
- •Who had any serious acute, chronic or progressive disease such as
- •History of cancer
- •Complicated diabetes mellitus
- •Advanced arteriosclerotic disease
- •Autoimmune disease
- •HIV infection or AIDS
- •Blood dyscrasias
- •Congestive heart failure
- •Renal failure
- •Severe malnutrition (Note: Subjects with mild asthma were eligible for enrollment. Subjects with moderate or severe asthma requiring routine use of inhaled or systemic corticosteroids were not eligible for enrollment)
- •Who had epilepsy, any progressive neurological disease or history of Guillain-Barre syndrome
- •Who had a history of anaphylaxis, serious vaccine reactions, or allergy to any vaccine component, including latex allergy
- •Who had a known or suspected impairment/alteration of immune function, either congenital or acquired or resulting from (for example):
- •Receipt of immunosuppressive therapy within 30 days prior to enrollment (systemic corticosteroids administered for more than 5 days, or in a daily dose > 1 mg/kg/day prednisone or equivalent during any of 30 days prior to enrollment, or cancer chemotherapy)
- •Receipt of immunostimulants
- •Receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 90 days prior to enrollment and for the full length of the study
- •Who were known to have a bleeding diathesis, or any condition that may be associated with a prolonged bleeding time;
- •Who have Down's syndrome or other known cytogenic disorders;
- •Who and/or whose families were planning to leave the area of the study site before the end of the study period;
- •Who had any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
- •Who were relatives of the study personnel.
研究组 & 干预措施
Placebo + Tdap + HPV
This group will receive Tdap, HPV and placebo concomitantly for the first vaccination. The second and third doses of HPV vaccine will be administered to all subjects 2 and 6 months after the first dose. All subjects will have serum samples collected at Visit 1 (baseline), Visit 2 (31 days) and Visit 5 (7 months after visit 1) for serology testing.
干预措施: Placebo + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine (Biological)
MenACWY-CRM + Tdap + HPV
This group will receive Tdap, HPV and MenACWY-CRM concomitantly. The second and third doses of HPV vaccine will be administered to this group 2 and 6 months after the first dose. All subjects will have serum samples collected at Visit 1 (baseline), Visit 2 (31 days) and Visit 5 (7 months after visit 1) for serology testing.
干预措施: MenACWY-CRM Conjugate Vaccine + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine (Biological)
结局指标
主要结局
Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo
时间窗: 1 month post Tdap vaccination.
The geometric mean concentrations (GMCs) of antibodies against pertussis antigens (PT, FHA and PRN), as measured by ELISA, following concomitant administration of Tdap with HPV and MenACWY-CRM as compared to concomitant administration of Tdap with HPV and placebo.
Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo
时间窗: 1 month post Tdap vaccination.
The percentages of subjects with anti-diphtheria and anti-tetanus antibody concentrations ≥ 0.1 IU/mL (as measured by ELISA) following concomitant administration of Tdap with HPV and MenACWY-CRM vaccine as compared to concomitant administration of Tdap with HPV and placebo.
次要结局
- Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo(Day 1-7 after any vaccination.)
- Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination.(1 month post MenACWY-CRM vaccination.)
- Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo(Throughout the study (Day 1 to Day 211).)