A Phase 3 Study of BIBP Diphtheria, Tetanus and Acellular Pertussis (Three Components) Combined Vaccine, Adsorbed

Study Overview
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Brief Summary
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The study will evaluate the safety, immunogenicity，immune persistence and lot-to-lot consistency of Diphtheria,Tetanus and Acellular Pertussis (Three Components) Combined Vaccine, Adsorbed, (DTacP) including 2 parts: PART 1 will evaluate the safety and immunogenicity of DTacP in health infants aged 2 months and 3 months compared with an adsorption Tetanus-diphtheria-acellular Pertussis (DTaP) Vaccine and Diphtheria,tetanus,pertussis(acellular,component),poliomyelitis(inactivated) vaccine(absorbed) and Haemophilus influenzae type b conjugate vaccine (PENTAXIM)，compare the safety and immunogenicity of DTacP with different immunization schedules, and observe the immune persistence. PART 2 will evaluate the lot-to-lot consistency of DTacP in health infants aged 3 months with the 3-dose schedule of 3-4-5 month.

Official Title
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A Randomized, Blinded, Parallel Controlled Phase 3 Clinical Study to Evaluate the Safety and Immunogenicity of the Diphtheria, Tetanus and Three-components Acellular Pertussis Combined Vaccine, Adsorbed in Healthy Infants at the Age of 2 Months and 3 Months

Conditions
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Whooping Cough, Diphtheria, Tetanus

Intervention / Treatment
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* Biological: Diphtheria,Tetanus and Acellular Pertussis (Three Components) Combined Vaccine, Adsorbed
* Biological: Diphtheria,Tetanus and Acellular Pertussis Combined Vaccine, Adsorbed
* Biological: Diphtheria,tetanus,pertussis(acellular,component),poliomyelitis(inactivated) vaccine(absorbed) and Haemophilus influenzae type b conjugate vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects aged 2months (60-89 days) and 3months (90-119 days) ； Willing to provide proof of identity Subjects aged 2 months have not been vaccinated with DTaP, IPV, Hib, or 13-valent pneumococcal polysaccharide conjugate vaccine; Subjects of 3 months have not been inoculated with DTaP vaccine, and IPV (only group A3）； Subjects'guardians or trustees are able to understand and sign the informed consent voluntarily, comply with the requirements of the clinical study plan. Exclusion Criteria: With temperature >37.0°C on axillary setting before vacciation; With a medical history of diphtheria, pertussis or tetanus; Had contact with individuals with confirmed pertussis, diphtheria and tetanus diseases in their families in the past 30 days; Premature birth (delivery before the 37th week of pregnancy)or low birth weight (birth weight< <2500g); History of dystocia, suffocation rescue, neurological damage; With congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc. History of epilepsy, convulsions or convulsions, or have a family history of mental illness; History of abnormal blood coagulation (such as coagulation factor deficiency, coagulopathy); Had received immune enhancement or inhibitor therapy (continuous oral or instillation for more than 14 days); History of severe allergic reactions to vaccination, such as difficulty breathing, urticaria; Any prior administration of blood products in last 3 month; Any prior administration of attenuated live vaccine in last 14 days; Any prior administration of subunit or inactivated vaccines in last 7 days; Plans to participate in or is participating in any other drug clinical study; Has any other factors judged by investigators that make them unfit to participate in the clinical trial

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: A1<br>subjects aged 3 months receive 3 doses of vaccines with a interval of 30 days for primary immunization, and a booster dose at 18 month old | Biological: Diphtheria,Tetanus and Acellular Pertussis (Three Components) Combined Vaccine, Adsorbed<br>* Intramuscular injection<br>* Other names: DTacP;|
| Active Comparator: A2<br>subjects aged 3 months receive 3 doses of vaccines with a interval of 30 days for primary immunization, and a booster dose at 18 month old | Biological: Diphtheria,Tetanus and Acellular Pertussis Combined Vaccine, Adsorbed<br>* Intramuscular injection<br>* Other names: DTaP;|
| Active Comparator: A3<br>subjects aged 3 months receive 3 doses of vaccines with a interval of 30 days for primary immunization, and a booster dose at 18 month old | Biological: Diphtheria,tetanus,pertussis(acellular,component),poliomyelitis(inactivated) vaccine(absorbed) and Haemophilus influenzae type b conjugate vaccine<br>* Intramuscular injection<br>* Other names: PENTAXIM;|
| Experimental: B1<br>subjects aged 2 months receive 3 doses of vaccines with a interval of 30 days for primary immunization, and a booster dose at 18 month old | Biological: Diphtheria,Tetanus and Acellular Pertussis (Three Components) Combined Vaccine, Adsorbed<br>* Intramuscular injection<br>* Other names: DTacP;|
| Active Comparator: B2<br>subjects aged 2 months receive 3 doses of vaccines with a interval of 30 days for primary immunization, and a booster dose at 18 month old | Biological: Diphtheria,Tetanus and Acellular Pertussis Combined Vaccine, Adsorbed<br>* Intramuscular injection<br>* Other names: DTaP;|
| Experimental: B3<br>subjects aged 2 months receive 3 doses of vaccines with a interval of 2 months for primary immunization, and a booster dose at 18 month old | Biological: Diphtheria,Tetanus and Acellular Pertussis (Three Components) Combined Vaccine, Adsorbed<br>* Intramuscular injection<br>* Other names: DTacP;|
| Experimental: C1<br>subjects aged 3 months receive 3 doses of lot-1 vaccines with a interval of 30 days for primary immunization | Biological: Diphtheria,Tetanus and Acellular Pertussis (Three Components) Combined Vaccine, Adsorbed<br>* Intramuscular injection<br>* Other names: DTacP;|
| Experimental: C2<br>subjects aged 3 months receive 3 doses of lot-2 vaccines with a interval of 30 days for primary immunization | Biological: Diphtheria,Tetanus and Acellular Pertussis (Three Components) Combined Vaccine, Adsorbed<br>* Intramuscular injection<br>* Other names: DTacP;|
| Experimental: C3<br>subjects aged 3 months receive 3 doses of lot-3 vaccines with a interval of 30 days for primary immunization | Biological: Diphtheria,Tetanus and Acellular Pertussis (Three Components) Combined Vaccine, Adsorbed<br>* Intramuscular injection<br>* Other names: DTacP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The seroconversion rate of anti-pertussis toxoid , anti-filamentous hemagglutinin, anti-Pertactin, anti-diphtheria toxoid and anti-tetanic antibody | seroconversion is defined as post-third dose antibody concentrations ≥ protective antibody concentration if pre-vaccination concentration is < protective antibody concentration, or ≥ 4 x protective antibody concentration if pre-vaccination concentrations ≥ protective antibody concentration. | 1 month after Dose 3 | 
| Geometric Mean Concentrations (GMCs) of anti-pertussis toxoid , anti-filamentous hemagglutinin, anti-Pertactin, anti-diphtheria toxoid and anti-tetanic antibody | As measured at the central laboratory | 1 month after Dose 3 | 
| Percentage of participants reporting local reactions | As elicited by investigational site staff | Day 7 post-each dose | 
| Percentage of participants reporting systemic events | As elicited by investigational site staff | Day 7 post-each dose | 
| Percentage of participants reporting adverse events | As elicited by investigational site staff | within 30 days post-each dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The seropositivity rate of anti-pertussis toxoid , anti-filamentous hemagglutinin, anti-Pertactin, anti-diphtheria toxoid and anti-tetanic antibody | Seropositivity is defined as post-3 dose antibody concentrations ≥ protective antibody concentration | Day 30 post-dose 3 | 
| Geometric Mean Concentrations (GMCs) of anti-pertussis toxoid , anti-filamentous hemagglutinin, anti-Pertactin, anti-diphtheria toxoid and anti-tetanic antibody | As measured at the central laboratory | before dose 4 at 18 months old(booster) | 
| The seropositivity rate of anti-pertussis toxoid , anti-filamentous hemagglutinin, anti-Pertactin, anti-diphtheria toxoid and anti-tetanic antibody | Seropositivity is defined as antibody concentrations ≥ protective antibody concentration | before dose 4 at 18 months old(booster) | 
| Geometric Mean Concentrations (GMCs) of anti-pertussis toxoid , anti-filamentous hemagglutinin, anti-Pertactin, anti-diphtheria toxoid and anti-tetanic antibody | As measured at the central laboratory | Day 30 post-dose 4 at 18 months old(booster) | 
| The seropositivity rate of anti-pertussis toxoid , anti-filamentous hemagglutinin, anti-Pertactin, anti-diphtheria toxoid and anti-tetanic antibody | eropositivity is defined as antibody concentrations ≥ protective antibody concentration | Day 30 post-dose 4 at 18 months old(booster) |