Phase 3 Study of A Group A, C Polysaccharide Meningococcal and Type b Haemophilus Influenzal Conjugate Vaccine

Study Overview
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Brief Summary
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Haemophilus influenzae is an important pathogen which can cause primary infection and respiratory viral infection in infants and leaded to secondary infections. The infection of haemophilus is a major cause of morbidity and mortality in infants and children. At present, the developed conjugant Hib vaccine is proved to be safe and effective. Because Hib vaccine can prevent meningitis, pneumonia, epiglottis inflammation and other serious infection caused by Hib bacteria, the WHO suggested that Hib vaccine should be included in the infant's normal immune programming. Since the use of meningitis aureus polysaccharide vaccine, incidence of a disease in recent years is declined and maintain to the level of 0.5 per 1/100 thousand. But meningitis aureus polysaccharide vaccine with a relatively poor immune response in the infants under the age of two, and the remaining 60% with a low antibody level and a short duration. The immunogenicity and safety of this vaccine has been proved in older children aged 6-23 months and 2-5 years. And in the phase I study which was conducted in February, 2012, the safety profile of this vaccine is proved to be acceptable in infants aged 3-5 months. The phase III study is aimed to further evaluate the safety and the immunization of the vaccine. The objective of this study is to evaluate the safety of the group A, C polysaccharide meningococcal and type b haemophilus influenzal conjugate vaccine.

Official Title
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Immunogenicity and Safety Study of A Group A, C Polysaccharide Meningococcal and Type b Haemophilus Influenzal Conjugate Vaccine in Aged 3-5 Months: A Phase 3 Clinical Trial

Conditions
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Meningitis, Influenza

Intervention / Treatment
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* Biological: A+C+hib Conjugate Vaccine
* Biological: Placebo
* Biological: A+C Vaccine
* Biological: Hib vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects aged 3 to 5 months, normal intelligence. The subjects' guardians are able to understand and sign the informed consent. Healthy subjects confirmed by medical history questioning, physical examination and clinical decision and in accordance with vaccination requirements of the investigational vaccine. Subjects who can comply with the requirements of the clinical trial program according to the researcher's views. Subjects who have never received group A, C polysaccharide meningococcal vaccine and type b haemophilus Influenzal vaccine. Subjects with temperature<=37°C on axillary setting. Exclusion Criteria for the first vaccination: Subject who has a medical history of Meningitis; Subject who has a medical history of any of the following: allergies, seizures, epilepsy, encephalopathy history and so on; Subject who is allergic with tetanus toxoid components; Subject suffering from thrombocytopenia or other coagulation disorder may lead to contraindication to intramuscular injection; Subject who has a history of allergic reactions; Any known immunological dysfunction; Had received gamma globulin or immune globulin, in the past two weeks Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with IM injections or blood draws Any acute infections in last 7 days Any prior administration of immunodepressant or corticosteroids in last 6month Any prior administration of other research medicines in last 1 month Any prior administration of attenuated live vaccine in last 28 days Any prior administration of subunit or inactivated vaccines in last 14 days, such as pneumococcal vaccine Subject suffering from congenital malformations, developmental delay or serious chronic disease; Any acute infections Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives Exclusion Criteria for the second or third vaccination: Had any Grade 3 or Grade 4 adverse reactions or events associated with investigational vaccine occurred since the vaccination Any situation meets the exclusion criteria for first dose; Any condition the investigator believed may affect the evaluation of the vaccine.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 5 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A+C+hib Conjugate Vaccine<br>600 infants aged 3-5 months, will be vaccinated on day0, 28, 56 | Biological: A+C+hib Conjugate Vaccine<br>* The group A, C polysaccharide meningococcal and type b haemophilus influenzal conjugate vaccine (Wuxi Royal Biological Co., LTD, 20110101) will be administered on one arm, intramuscularly, per 0.5ml dose<br>Biological: Placebo<br>* Placebo will be administered intramuscularly on the other arm, intramuscularly, per 0.5ml dose<br>|
| Active Comparator: Walvax AC vaccine, Pasteur Hib vaccine<br>300 infants aged 3-5 months, will be vaccinated on day0, 28, 56 | Biological: A+C Vaccine<br>* The group A, C polysaccharide meningococcal vaccine (Yunnan Walvax Biotechnology Co., LTD, 20101202) will be administered intramuscularly on one arm, per 0.5ml dose<br>Biological: Hib vaccine<br>* The type b haemophilus influenzal vaccine (Sanofi Pasteur Limited) will be administered intramuscularly on the other arm, per 0.5ml dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The seroconversion rate of antibody against group A, C polysaccharide meningitis in infants aged 3-5 months | the seroconversion rate of antibody against group A, C polysaccharide meningitis in infants aged 3-5 months when measured 4 weeks (28±3 days) after the infant series (three doses, 28 day apart). | 4 weeks (28±3 days) after the infant series | 
| The seroconversion rate of antibody against type b haemophilus influenza in infants aged 3-5 months | the seroconversion rate of antibody against type b haemophilus Influenza in infants aged 3-5 months when measured 4 weeks (28±3 days) after the infant series (three doses, 28 day apart) | 4 weeks (28±3 days) after the infant series | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse reactions after the first vaccination in infants aged 3-5 months | adverse reactions of the investigational vaccines in healthy infants aged 3-5 months for 7 days after the first vaccination | 7 days after the first vaccination | 
| adverse reactions after the second vaccination in infants aged 3-5 months | adverse reactions of the investigational vaccines in healthy infants aged 3-5 months for 7 days after the second vaccination | 7 days after the second vaccination | 
| adverse reactions after the third vaccination in infants aged 3-5 months | adverse reactions of the investigational vaccines in healthy infants aged 3-5 months for 7 days after the third vaccination | 7 days after the third vaccination | 
| GMT of antibody against group A, C polysaccharide meningitis in infants aged 3-5 months | GMT of antibody against group A, C polysaccharide meningitis in infants aged 3-5 months 4 weeks (28±3 days) after the infant series (three doses, 28 day apart) | 4 weeks (28±3 days) after the infant series | 
| GMT of antibody against type b haemophilus Influenza in serum in infants aged 3-5 months | GMT of antibody against type b haemophilus Influenza in infants aged 3-5 months 4 weeks (28±3 days) after the infant series (three doses, 28 day apart) | 4 weeks (28±3 days) after the infant series | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunogenicity, safety, group A, C polysaccharide meningitis, type b haemophilus Influenza