A Phase II, Randomized, Open Label, Controlled, Multicenter Study to Evaluate the Safety, Immunogenicity and Induction of Immunological Memory After Two or Three Doses of Novartis (Formerly Chiron) Meningococcal ACWY Conjugate Vaccine Administered to Healthy Infants at 2, 3, 4 or 2, 4, 6 Months of Age
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 601
- 试验地点
- 3
- 主要终点
- Percentages of Subjects With hSBA Titers ≥ 1:4 Against N. Meningitidis Serogroups A, C, W, and Y Following 3 Doses of MenACWY Ad+ Vaccine
研究概览
简要总结
The purpose of this study is to evaluate the safety, immunogenicity and induction of immune memory after two or three doses of Novartis (Formerly Chiron) Meningococcal ACWY Conjugate Vaccine administered to healthy infants.
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
- None
入排标准
- 年龄范围
- 2 Months 至 6 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Individuals eligible for enrollment in this study were male, and female infants:
- •Who were healthy 2-month old infants (55-89 days, inclusive) born after full term pregnancy with an estimated gestational age ≥ 37 weeks, and a birth weight ≥ 2.5 kg;
- •For whom a parent/legal guardian has given written informed consent after the nature of the study has been explained;
- •Who were available for all the visits scheduled in the study;
- •Who were in good health as determined by:
- •Medical history;
- •Physical examination;
- •Clinical judgment of the investigator.
排除标准
- •Ineligible for the study were infants:
- •Whose parents/legal guardians were unwilling, or unable to give written informed consent for the subject to participate in the study;
- •Who previously received any meningococcal vaccine;
- •Who received prior vaccination with D, T, P (acellular, or whole cell), IPV, or OPV, HBV, H influenzae type b (Hib), or Pneumococcus;
- •Who had a previously ascertained or suspected disease caused by N meningitidis, C diphtheriae, C tetani, Poliovirus, Hepatitis B, Hib, Pneumococcus, or B pertussis (history of laboratory-confirmed or clinical condition of spasmodic cough for a period ≥ 2 weeks associated with apnea or whooping cough);
- •Who had household contact with and/or intimate exposure to an individual with laboratory-confirmed N meningitis (serogroups A, C, W-135, or Y), B pertussis, Hib, C diphtheriae, Polio, or pneumococcal infection since birth;
- •Who had a history of any anaphylactic shock, asthma, urticaria, or other allergic reaction after previous vaccinations, or known hypersensitivity to any vaccine component;
- •Who had experienced significant acute or chronic infection within the previous 7 days, or fever (≥ 38.0°C) within the previous 3 days;
- •Who had any present, or suspected serious, acute (e.g., leukemia, lymphomas), or chronic disease (e.g., with signs of cardiac, renal failure, or severe malnutrition, or insulin-dependent diabetes); or progressive neurological disease; or a genetic anomaly or known cytogenic disorders (e.g., Downs syndrome);
- •Who had a known or suspected autoimmune disease or impairment /alteration of immune function resulting from (for example):
- •receipt of any immunosuppressive therapy since birth;
- •receipt of immunostimulant since birth;
- •receipt of any systemic corticosteroid since birth.
- •Who had a suspected or known HIV infection, or HIV-related disease;
- •Who had ever received blood, blood products and/or plasma derivatives, or any parenteral immunoglobulin preparation;
- •Who had a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time;
- •Who had a history of seizure disorder:
- •Febrile seizure;
- •Any other seizure disorder.
- •Who had taken systemic antibiotics (either oral or parenteral) within the previous 14 days (EXCEPTION: subjects who received an oral or parenteral β-lactam antibiotic [examples: penicillin, amoxicillin, ceftriaxone, cefuroxime, cephalexin, etc.] may be enrolled 7 days following the last dose);
- •Who with their parents/legal guardians 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 had taken any antipyretic medication in the previous 6 hours.
研究组 & 干预措施
UK234+ (MenACWY Ad+ at 2, 3, 4 m)
Three doses of MenACWY Ad+ vaccine were given at 1-month intervals concomitantly with DTaPHibIPV at 2, 3, and 4 months of age in the UK group. A fourth dose of MenACWY Ad+ was given at 12 months of age.
干预措施: MenACWY Ad+ (MenACWY-CRM, adjuvanted formulation) (Biological)
CA24- (MenACWY Ad- at 2, 4 m)
Two doses of MenACWY Ad- vaccine were given at a 2-month interval concomitantly with DTaPHibIPV, HBV, and Prevnar at 2 and 4 months of age.One dose of MenACWY Ad- vaccine or one reduced dose of MenACWY PS vaccine was given concomitantly with MMR (and Prevnar, if available) at 12 months of age.
干预措施: Prevnar (pneumococcal polysaccharide serotypes 4, 9V, 14, 18C, 19F, 23F & 6B conjugated to the CRM197) (Biological)
CA24- (MenACWY Ad- at 2, 4 m)
Two doses of MenACWY Ad- vaccine were given at a 2-month interval concomitantly with DTaPHibIPV, HBV, and Prevnar at 2 and 4 months of age.One dose of MenACWY Ad- vaccine or one reduced dose of MenACWY PS vaccine was given concomitantly with MMR (and Prevnar, if available) at 12 months of age.
干预措施: DTaPHibIPV (Diphtheria, Tetanus, acellular Pertussis, H. Influenzae type b, Inactivated Poliovaccine) (Biological)
UK234+ (MenACWY Ad+ at 2, 3, 4 m)
Three doses of MenACWY Ad+ vaccine were given at 1-month intervals concomitantly with DTaPHibIPV at 2, 3, and 4 months of age in the UK group. A fourth dose of MenACWY Ad+ was given at 12 months of age.
干预措施: DTaPHibIPV (Diphtheria, Tetanus, acellular Pertussis, H. Influenzae type b, Inactivated Poliovaccine) (Biological)
UK24+ (MenACWY Ad+ at 2, 4 m)
Two doses of MenACWY Ad+ vaccine were given at a 2-month interval concomitantly with DTaPHibIPV at 2 and 4 months of age. A third dose of MenACWY Ad+ vaccine was given at 12 months of age.
干预措施: MenACWY Ad+ (MenACWY-CRM, adjuvanted formulation) (Biological)
UK24+ (MenACWY Ad+ at 2, 4 m)
Two doses of MenACWY Ad+ vaccine were given at a 2-month interval concomitantly with DTaPHibIPV at 2 and 4 months of age. A third dose of MenACWY Ad+ vaccine was given at 12 months of age.
干预措施: DTaPHibIPV (Diphtheria, Tetanus, acellular Pertussis, H. Influenzae type b, Inactivated Poliovaccine) (Biological)
UKMenC (Menjugate at 2, 4 m)
Two doses of Menjugate were given at a 2-month interval concomitantly with DTaPHibIPV at 2 and 4 months of age. One dose of MenACWY Ad+ vaccine was given at 12 months of age.
干预措施: MenACWY Ad+ (MenACWY-CRM, adjuvanted formulation) (Biological)
UKMenC (Menjugate at 2, 4 m)
Two doses of Menjugate were given at a 2-month interval concomitantly with DTaPHibIPV at 2 and 4 months of age. One dose of MenACWY Ad+ vaccine was given at 12 months of age.
干预措施: DTaPHibIPV (Diphtheria, Tetanus, acellular Pertussis, H. Influenzae type b, Inactivated Poliovaccine) (Biological)
UKMenC (Menjugate at 2, 4 m)
Two doses of Menjugate were given at a 2-month interval concomitantly with DTaPHibIPV at 2 and 4 months of age. One dose of MenACWY Ad+ vaccine was given at 12 months of age.
干预措施: Menjugate (Men C conjugated vaccine) (Biological)
CA246+ (MenACWY Ad+ at 2, 4, 6 m)
Three doses of MenACWY Ad+ vaccine were given at 2-month intervals concomitantly with DTaPHibIPV, HBV, and Prevnar at 2, 4, and 6 months of age of the Canadian group (Prevnar at 6 months was optional and was given if available).One subgroup of subjects was given a reduced dose (1/5) of MenACWY PS vaccine concomitantly with MMR (and Prevnar, if available) at 12 months of age. Another subgroup was administered one dose of MMR (and Prevnar, if available) at 12 months of age.
干预措施: MenACWY Ad+ (MenACWY-CRM, adjuvanted formulation) (Biological)
CA246+ (MenACWY Ad+ at 2, 4, 6 m)
Three doses of MenACWY Ad+ vaccine were given at 2-month intervals concomitantly with DTaPHibIPV, HBV, and Prevnar at 2, 4, and 6 months of age of the Canadian group (Prevnar at 6 months was optional and was given if available).One subgroup of subjects was given a reduced dose (1/5) of MenACWY PS vaccine concomitantly with MMR (and Prevnar, if available) at 12 months of age. Another subgroup was administered one dose of MMR (and Prevnar, if available) at 12 months of age.
干预措施: MenACWY PS (MenACWY-CRM, polysaccharide vaccine) (Biological)
CA246+ (MenACWY Ad+ at 2, 4, 6 m)
Three doses of MenACWY Ad+ vaccine were given at 2-month intervals concomitantly with DTaPHibIPV, HBV, and Prevnar at 2, 4, and 6 months of age of the Canadian group (Prevnar at 6 months was optional and was given if available).One subgroup of subjects was given a reduced dose (1/5) of MenACWY PS vaccine concomitantly with MMR (and Prevnar, if available) at 12 months of age. Another subgroup was administered one dose of MMR (and Prevnar, if available) at 12 months of age.
干预措施: HBV (Hepatitis B vaccine) (Biological)
CA246+ (MenACWY Ad+ at 2, 4, 6 m)
Three doses of MenACWY Ad+ vaccine were given at 2-month intervals concomitantly with DTaPHibIPV, HBV, and Prevnar at 2, 4, and 6 months of age of the Canadian group (Prevnar at 6 months was optional and was given if available).One subgroup of subjects was given a reduced dose (1/5) of MenACWY PS vaccine concomitantly with MMR (and Prevnar, if available) at 12 months of age. Another subgroup was administered one dose of MMR (and Prevnar, if available) at 12 months of age.
干预措施: Prevnar (pneumococcal polysaccharide serotypes 4, 9V, 14, 18C, 19F, 23F & 6B conjugated to the CRM197) (Biological)
CA246+ (MenACWY Ad+ at 2, 4, 6 m)
Three doses of MenACWY Ad+ vaccine were given at 2-month intervals concomitantly with DTaPHibIPV, HBV, and Prevnar at 2, 4, and 6 months of age of the Canadian group (Prevnar at 6 months was optional and was given if available).One subgroup of subjects was given a reduced dose (1/5) of MenACWY PS vaccine concomitantly with MMR (and Prevnar, if available) at 12 months of age. Another subgroup was administered one dose of MMR (and Prevnar, if available) at 12 months of age.
干预措施: MMR (Measles, Mumps and Rubella vaccine) (Biological)
CA246+ (MenACWY Ad+ at 2, 4, 6 m)
Three doses of MenACWY Ad+ vaccine were given at 2-month intervals concomitantly with DTaPHibIPV, HBV, and Prevnar at 2, 4, and 6 months of age of the Canadian group (Prevnar at 6 months was optional and was given if available).One subgroup of subjects was given a reduced dose (1/5) of MenACWY PS vaccine concomitantly with MMR (and Prevnar, if available) at 12 months of age. Another subgroup was administered one dose of MMR (and Prevnar, if available) at 12 months of age.
干预措施: DTaPHibIPV (Diphtheria, Tetanus, acellular Pertussis, H. Influenzae type b, Inactivated Poliovaccine) (Biological)
CA24+ (MenACWY Ad+ at 2, 4 m)
Two doses of MenACWY Ad+ vaccine were given at a 2-month interval concomitantly with DTaPHibIPV, HBV, and Prevnar at 2 and 4 months of age.One dose of MenACWY Ad+ vaccine or one reduced dose (1/5) of MenACWY PS vaccine was given concomitantly with MMR (and Prevnar, if available) at 12 months of age.
干预措施: MenACWY Ad+ (MenACWY-CRM, adjuvanted formulation) (Biological)
CA24+ (MenACWY Ad+ at 2, 4 m)
Two doses of MenACWY Ad+ vaccine were given at a 2-month interval concomitantly with DTaPHibIPV, HBV, and Prevnar at 2 and 4 months of age.One dose of MenACWY Ad+ vaccine or one reduced dose (1/5) of MenACWY PS vaccine was given concomitantly with MMR (and Prevnar, if available) at 12 months of age.
干预措施: MenACWY PS (MenACWY-CRM, polysaccharide vaccine) (Biological)
CA24+ (MenACWY Ad+ at 2, 4 m)
Two doses of MenACWY Ad+ vaccine were given at a 2-month interval concomitantly with DTaPHibIPV, HBV, and Prevnar at 2 and 4 months of age.One dose of MenACWY Ad+ vaccine or one reduced dose (1/5) of MenACWY PS vaccine was given concomitantly with MMR (and Prevnar, if available) at 12 months of age.
干预措施: HBV (Hepatitis B vaccine) (Biological)
CA24+ (MenACWY Ad+ at 2, 4 m)
Two doses of MenACWY Ad+ vaccine were given at a 2-month interval concomitantly with DTaPHibIPV, HBV, and Prevnar at 2 and 4 months of age.One dose of MenACWY Ad+ vaccine or one reduced dose (1/5) of MenACWY PS vaccine was given concomitantly with MMR (and Prevnar, if available) at 12 months of age.
干预措施: Prevnar (pneumococcal polysaccharide serotypes 4, 9V, 14, 18C, 19F, 23F & 6B conjugated to the CRM197) (Biological)
CA24+ (MenACWY Ad+ at 2, 4 m)
Two doses of MenACWY Ad+ vaccine were given at a 2-month interval concomitantly with DTaPHibIPV, HBV, and Prevnar at 2 and 4 months of age.One dose of MenACWY Ad+ vaccine or one reduced dose (1/5) of MenACWY PS vaccine was given concomitantly with MMR (and Prevnar, if available) at 12 months of age.
干预措施: MMR (Measles, Mumps and Rubella vaccine) (Biological)
CA24+ (MenACWY Ad+ at 2, 4 m)
Two doses of MenACWY Ad+ vaccine were given at a 2-month interval concomitantly with DTaPHibIPV, HBV, and Prevnar at 2 and 4 months of age.One dose of MenACWY Ad+ vaccine or one reduced dose (1/5) of MenACWY PS vaccine was given concomitantly with MMR (and Prevnar, if available) at 12 months of age.
干预措施: DTaPHibIPV (Diphtheria, Tetanus, acellular Pertussis, H. Influenzae type b, Inactivated Poliovaccine) (Biological)
UK24- (MenACWY Ad- at 2, 4 m)
Two doses of MenACWY Ad- vaccine were given at a 2-month interval concomitantly with DTaPHibIPV at 2 and 4 months of age. A third dose of MenACWY Ad- vaccine was given at 12 months of age.
干预措施: MenACWY Ad- (MenACWY-CRM, non adjuvanted formulation) (Biological)
UK24- (MenACWY Ad- at 2, 4 m)
Two doses of MenACWY Ad- vaccine were given at a 2-month interval concomitantly with DTaPHibIPV at 2 and 4 months of age. A third dose of MenACWY Ad- vaccine was given at 12 months of age.
干预措施: DTaPHibIPV (Diphtheria, Tetanus, acellular Pertussis, H. Influenzae type b, Inactivated Poliovaccine) (Biological)
CA24- (MenACWY Ad- at 2, 4 m)
Two doses of MenACWY Ad- vaccine were given at a 2-month interval concomitantly with DTaPHibIPV, HBV, and Prevnar at 2 and 4 months of age.One dose of MenACWY Ad- vaccine or one reduced dose of MenACWY PS vaccine was given concomitantly with MMR (and Prevnar, if available) at 12 months of age.
干预措施: MenACWY Ad- (MenACWY-CRM, non adjuvanted formulation) (Biological)
CA24- (MenACWY Ad- at 2, 4 m)
Two doses of MenACWY Ad- vaccine were given at a 2-month interval concomitantly with DTaPHibIPV, HBV, and Prevnar at 2 and 4 months of age.One dose of MenACWY Ad- vaccine or one reduced dose of MenACWY PS vaccine was given concomitantly with MMR (and Prevnar, if available) at 12 months of age.
干预措施: MenACWY PS (MenACWY-CRM, polysaccharide vaccine) (Biological)
CA24- (MenACWY Ad- at 2, 4 m)
Two doses of MenACWY Ad- vaccine were given at a 2-month interval concomitantly with DTaPHibIPV, HBV, and Prevnar at 2 and 4 months of age.One dose of MenACWY Ad- vaccine or one reduced dose of MenACWY PS vaccine was given concomitantly with MMR (and Prevnar, if available) at 12 months of age.
干预措施: HBV (Hepatitis B vaccine) (Biological)
结局指标
主要结局
Percentages of Subjects With hSBA Titers ≥ 1:4 Against N. Meningitidis Serogroups A, C, W, and Y Following 3 Doses of MenACWY Ad+ Vaccine
时间窗: Baseline and at 1 month after the 3 dose primary vaccination series
Immunogenicity was measured as the percentage of subjects with human serum bactericidal assay (hSBA) titers ≥ 1:4 and associated 95% CI, directed against N. Meningitidis serogroups A, C, W and Y, at the baseline and 1 month after primary vaccination by groups.
次要结局
- Percentages of Subjects With hSBA Titers ≥ 1:8 Against N. Meningitidis Serogroups A, C, W, and Y Following 3 Doses of MenACWY Ad+ Conjugate Vaccine(Baseline and 1 month after the 3 dose primary vaccination series)
- Percentages of Subjects With hSBA Titers ≥ 1:4 or ≥ 1:8 Against N. Meningitidis Serogroups A, C, W, and Y Following 2 Doses of Novartis MenACWY Ad+ or Novartis MenACWY Ad- Conjugate Vaccines(Baseline and 1 month after second vaccination)
- Geometric Mean hSBA Titers (GMT) After a Booster Dose of MenACWY Ad+ or Ad- Vaccine Conjugate in a Subgroup of Subjects Following Either 2 or 3 Doses of MenACWY Ad+ Vaccine or 2 Doses of MenACWY Ad- Conjugate Vaccines(at 12 months of age and 1 month after booster vaccination)
- Percentages of Subjects With hSBA Titers ≥ 1:4 and ≥ 1:8 Against N. Meningitidis Serogroups A, C, W and Y Following 2 Doses of Novartis MenACWY Ad+ Vaccine, Novartis MenACWY Ad- Vaccine or Novartis Menjugate Vaccine(at 12 months of age)
- Percentages of Subjects With hSBA Titers ≥ 1:4 and ≥ 1:8 Against N. Meningitidis Serogroup A, C, W and Y Following 3 Doses of Novartis MenACWY Ad+ Conjugate Vaccine(at 12 months of age)
- Percentages of Subjects With hSBA Titers ≥ 1:4 or ≥ 1:8 in Subjects Challenged With a Reduced Dose of Licensed Meningococcal ACWY PS Vaccine Following 3 Doses of Novartis MenACWY Ad+ Conjugate Vaccine(before challenge at 12 months of age and 1 month after PS challenge.)
- Geometric Mean hSBA Titers (GMTs) Following 3 Doses of MenACWY Ad+ Conjugate Vaccine(Baseline and 1 month after the 3 dose primary vaccination series)
- Geometric Mean hSBA Titers (GMTs) After 2 Doses of Novartis MenACWY Ad+ Vaccines, Novartis MenACWY Ad- Vaccine, or Novartis Menjugate Vaccine.(at 12 months of age)
- Geometric Mean hSBA Titers (GMTs) Following 3 Doses of Novartis MenACWY Ad+ Conjugate Vaccine(at 12 months of age)
- Geometric Mean hSBA Titer (GMTs) Following 2 Doses of MenACWY Ad+ and MenACWY Ad- Conjugate Vaccines(Baseline and 1 month after second vaccination)
- Percentages of Subjects With hSBA Titers ≥ 1:4 or ≥ 1:8 Against N. Meningitidis Serogroups A, C, W & Y After a Booster Dose of MenACWY Ad+ or Ad- Vaccine in a Subgroup of Subjects Following 2 or 3 Doses or MenACWY Ad+ or 2 Doses of MenACWY Ad- Vaccine(at 12 months of age and 1 month after booster vaccination)
- Percentages of Subjects With hSBA ≥ 1:4 and ≥ 1:8 of MenACWY Ad+ Conjugate Vaccine(Baseline and 1 month after the 2 or 3 dose primary vaccination series)
- Geometric Mean hSBA Titers (GMTs) in Subjects Challenged With a Reduced Dose of Licensed Meningococcal ACWY PS Vaccine Following 3 Doses of Novartis MenACWY Ad+ Conjugate Vaccine(before challenge at 12 months of age and 1 month after PS challenge.)
- ELISA GMT Concentrations for Routine Vaccines (Hib, Diphtheria, Tetanus, Hepatitis B) When Given Concomitantly With Novartis MenACWY Ad+ or Novartis MenACWY Ad- Conjugate Vaccines for Hib, Diphtheria, Tetanus, Hepatitis B(Baseline and 1 month after the 2 or 3 dose primary vaccination series)
- Percentages of Subjects With hSBA Titers ≥ 1:4 or ≥ 1:8 in Subjects Challenged With a Reduced Dose of Licensed Meningococcal ACWY PS Vaccine Following Two Doses of Novartis MenACWY Ad+ or MenACWY Ad- Conjugate Vaccine(Before challenge at 12 months of age and 1 month after PS challenge.)
- Percentages of Subjects With Antibody Response to Routine Vaccines (Hib, Diphtheria, Tetanus, Hepatitis B) When Routine Vaccines Are Given Concomitantly With Novartis MenACWY Ad+ or Novartis MenACWY Ad- Conjugate Vaccines(Baseline and 1 month after the 2 or 3 dose primary vaccination series)
- Geometric Mean hSBA Titers (GMTs) in Subjects Challenged With a Reduced Dose of Licensed Meningococcal ACWY PS Vaccine Following Two Doses of Novartis MenACWY Ad+ or MenACWY Ad- Conjugate Vaccine(Before challenge at 12 months of age and 1 month after PS challenge.)
- Percentages of Subjects With hSBA ≥ 1:4 and ≥ 1:8 in Subjects Challenged With a Reduced Dose of a Licensed Meningococcal ACWY PS Vaccine Following 2 or 3 Doses of MenACWY Ad+ Conjugate Vaccine(at 12 months of age and 1 month after PS challenge)
- Number of Subjects Reporting Solicited Local and Systemic Adverse Events After 2 or 3 Dose Primary Vaccination Series With MenACWY Ad+ or MenACWY Ad-(7 days after each vaccination)
- Number of Subjects Reporting Solicited Local and Systemic Adverse Events After MenACWY Ad+ and MenACWY Ad- Booster or Polysaccharide Challenge Administered at 12 Months of Age(7 days after vaccination at 12 months of age)
- Percentages of Subjects With hSBA ≥ 1:4 and ≥ 1:8 Against N. Meningitidis Serogroup C Following 2 Doses of MenACWY Ad+ or Ad- Conjugate Vaccine (Containing 5 μg of MenC Oligosaccharide) or 2 Doses of Menjugate (Containing 10 μg of MenC Oligosaccharide)(Baseline and 1 month after second vaccination)