Clinic Trial to Evaluate the Safety and Immunogenicity by Different Sequential Schedules of bOPV and IPV

Institute of Medical Biology, Chinese Academy of Medical Sciences

Status and phase: Completed; Phase 3

Conditions: Poliomyelitis

Treatments: Biological: 1-dose cIPV + 2-doses bOPV (Candy); Biological: 2-doses cIPV + 1-dose bOPV (Liquid); Biological: 1-dose sIPV + 2-doses bOPV (Candy); Biological: 2-doses cIPV + 1-dose tOPV (Liquid); Biological: 1-dose cIPV + 2-doses bOPV (Liquid); Biological: 2-doses sIPV + 1-dose bOPV (Liquid); Biological: 2-doses cIPV + 1-dose bOPV (Candy); Biological: 2-doses sIPV + 1-dose bOPV (Candy); Biological: 2-doses cIPV + 1-dose tOPV (Candy); Biological: 2-doses sIPV + 1-dose tOPV (Candy); Biological: 1-dose sIPV + 2-doses bOPV (Liquid); Biological: 2-doses sIPV + 1-dose tOPV (Liquid)

Study type: Interventional

Funder types: Other

Identifiers

NCT03614702

bOPV-PRO-001

Details and patient eligibility

About

With the progress of the eradication of polio, bivalent oral attenuated live poliomyelitis vaccine against type 1 and 3 (bOPV) and inactivated poliomyelitis vaccine made by Sabin strain (sIPV) are required to use in the "Strategy of Polio Eradication & Endgame Strategic Plan 2013-2018" worldwide.

To evaluate the safety and immunogenicity by different sequential schedules of bOPV/tOPV with IPV(sIPV/cIPV), a randomized, double blind, single center and parallel phase Ⅲ clinic trial was performed in Infants of two-month-old in Guangxi Province, China.

Full description

According to the requirement of the Strategy of Polio Eradication & Endgame Strategic Plan 2013-2018, bivalent oral attenuated live poliomyelitis vaccine against type 1 and 3 (bOPV) and inactivated poliomyelitis vaccine made by Sabin strain (sIPV) need to be used to eradiation both the wild poliovirus and vaccine-derived poliovirus.

By studying different sequential immunization schedules of bOPV(candy/liquid) with IPV(cIPV/sIPV) to evaluate the safety and immunogenicity of bivalent oral poliomyelitis vaccine co-administered with IPV in healthy Infants. A randomized, double blind, single center and parallel phase Ⅲ clinic trial was performed in Guangxi Province in China. A total of 1200 infants at 2 months old were selected, and randomly divided into 12 different groups (100 individuals were included in each group) administrated the vaccines at 0, 28, 56 days schedule. The bOPV(bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3), tOPV(trivalent OPV against type 1, type 2 and type 3), sIPV (Inactivated Poliomyelitis Vaccine Made from Sabin Strains)and conventional IPV (Inactivated Poliomyelitis Vaccine Made from Wild Polio Strains) were assign to different group of sequential immunization schedules.

The detail of each group as following:

1)1-dose cIPV + 2-doses bOPV (Candy); 2)1-dose sIPV + 2-doses bOPV (Candy); 3)2-doses cIPV + 1-dose bOPV (Candy); 4)2-doses sIPV + 1-dose bOPV (Candy); 5)2-doses cIPV + 1-dose tOPV (Candy); 6)2-doses sIPV + 1-dose tOPV (Candy); 7)1-dose cIPV + 2-doses bOPV (Liquid); 8)1-dose sIPV + 2-doses bOPV (Liquid); 9)2-doses cIPV + 1-dose bOPV (Liquid); 10)2-doses sIPV + 1-dose bOPV (Liquid); 11)2-doses cIPV + 1-dose tOPV (Liquid); 12)2-doses sIPV + 1-dose tOPV (Liquid).

Blood Sample was collected before vaccination and 28 days after the third dose of vaccination. Neutralization antibody against type I, Type I and Type III poliomyelitis virus were detected to evaluate the seroprotection rates and antibody geometric mean concentrations. The safety of different sequential schedule immunization for the vaccines also been monitored.

The first 10% of subjects in each research site，fecal samples were collected to test polio virus shedding.The 7 times are before the second dose immunization and the 7、14、28 days after the second and the third dose immunization.

Enrollment: 1,200 patients

Sex: All

Ages: 2 to 2 months old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Term pregnancy (37-42 weeks), birth weight meets the standards (over 2500g), aged from 60 days to 90 days old;
• parent(s) or guardians are able to understand and sign informed consent for participation;
• Participants or guardians are able to attend all planned clinical appointment and obey and follow all study instructions;
• subject didn't administrate with any immunoglobulin after birth (except the Hepatitis B specific immunoglobulin) and did not administrate any other live vaccines within 28 days or inactivated vaccines within 14 days;
• Axillary temperature ≤37.1℃.

Exclusion criteria

Subjects will not be eligible for the study if any of the following criteria is met：

• Subject who has a medical histroy with Hypersensitiveness, eclampsia, epilepsy, cerebropathia and neurological illness
• Subject who is allergy to Streptomycin, neomycin and polymyxin B
• Subject with immunodeficency or are in the process of immunosuppressor therapy
• Clinical diagnosis of poliomyelitis;
• Acute febrile disease or infectious disease;
• Labor abnormal, asphyxiation rescues, congenital abnormality, developmental disability, serious chronic diseases;
• Allergic to any ingredient of vaccine or with allergy history to any vaccine;
• Taking orally injecting of steroid hormone over 14 days in the recent month;
• Febrile (temperature ≥ 38.0°C) in three days;
• Diarrhea with one week (more than 3 motions a day);
• Taking part in another clinical trail;
• Any OPV vaccination contraindication and any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,200 participants in 12 patient groups

1-dose cIPV + 2-doses bOPV (Candy)

Experimental group

Description:

cIPV: Inactivated Poliomyelitis Vaccine Made from Wild Polio Strains Produced by Sanofi Pasteur Co., Ltd. 0.5ml/dose bOPV (Candy): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 in Dragee Candy (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences . 1g/pill,10 pills/pach,one pill each time; each pill containing polio virus≥5.92 lgCCID50 including type1 polio virus≥5.8 lgCCID50，type 3 polio virus ≥5.3lgCCID50.

Treatment:

Biological: 1-dose cIPV + 2-doses bOPV (Candy)

1-dose sIPV + 2-doses bOPV (Candy)

Experimental group

Description:

sIPV: Inactivated Poliomyelitis Vaccine Made from Sabin Strains Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences 0.5ml/dose bOPV (Candy): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 in Dragee Candy (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 1g/pill,10 pills/pach,one pill each time;each pill containing polio virus≥5.92 lgCCID50 including type1 polio virus≥5.8 lgCCID50，type 3 polio virus ≥5.3lgCCID50.

Treatment:

Biological: 1-dose sIPV + 2-doses bOPV (Candy)

2-doses cIPV + 1-dose bOPV (Candy)

Experimental group

Description:

cIPV: Inactivated Poliomyelitis Vaccine Made from Wild Polio Strains Produced by Sanofi Pasteur Co., Ltd. 0.5ml/dose bOPV (Candy): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 in Dragee Candy (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 1g/pill,10 pills/pach,one pill each time; each pill containing polio virus≥5.92 lgCCID50 including type1 polio virus≥5.8 lgCCID50，type 3 polio virus ≥5.3lgCCID50

Treatment:

Biological: 2-doses cIPV + 1-dose bOPV (Candy)

2-doses sIPV + 1-dose bOPV (Candy)

Experimental group

Description:

sIPV: Inactivated Poliomyelitis Vaccine Made from Sabin Strains Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 0.5ml/dose bOPV (Candy): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 in Dragee Candy (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 1g/pill,10 pills/pach,one pill each time; each pill containing polio virus≥5.92 lgCCID50 including type1 polio virus≥5.8 lgCCID50，type 3 polio virus ≥5.3lgCCID50

Treatment:

Biological: 2-doses sIPV + 1-dose bOPV (Candy)

2-doses cIPV + 1-dose tOPV (Candy)

Experimental group

Description:

cIPV: Inactivated Poliomyelitis Vaccine（Vero） Made from Wild Polio Strains Produced by Sanofi Pasteur Co., Ltd. 0.5ml/dose tOPV (Candy): Trivalent oral attenuated live poliomyelitis vaccine against type 1, type 2 and type 3 in Dragee Candy (Human Diploid Cell) Produced by Beijing Tiantan Biological Products Co., Ltd. 1g/pill,10 pills/pach;each pill containing polio virus≥5.95 lgCCID50 including type1 polio virus≥5.8 lgCCID50，type 2 polio virus ≥4.8lgCCID50，type 3 polio virus ≥5.3lgCCID50

Treatment:

Biological: 2-doses cIPV + 1-dose tOPV (Candy)

2-doses sIPV + 1-dose tOPV (Candy)

Experimental group

Description:

sIPV: Inactivated Poliomyelitis Vaccine Made from Sabin Strains Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences 0.5ml/dose tOPV (Candy): Trivalent oral attenuated live poliomyelitis vaccine against type 1, type 2 and type 3 in Dragee Candy (Human Diploid Cell) Produced by Beijing Tiantan Biological Products Co., Ltd.1g/pill,10 pills/pach,one pills each time;each pill containing polio virus≥5.95 lgCCID50 including type1 polio virus≥5.8 lgCCID50，type 2 polio virus ≥4.8lgCCID50，type 3 polio virus ≥5.3lgCCID50

Treatment:

Biological: 2-doses sIPV + 1-dose tOPV (Candy)

1-dose cIPV + 2-doses bOPV (Liquid)

Experimental group

Description:

cIPV: Inactivated Poliomyelitis Vaccine（Vero） Made from Wild Polio Strains Produced by Sanofi Pasteur Co., Ltd. 0.5ml/dose bOPV (Liquid): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 0.5ml or 1.0ml each bottle;total content of polio virus≥7.12lgCCID50/ml，type1 polio virus≥7.0 lgCCID50/ml，type 3 polio virus ≥6.5lgCCID50/ml.(2 drops per person;be be equivalent to 0.1ml each person )

Treatment:

Biological: 1-dose cIPV + 2-doses bOPV (Liquid)

1-dose sIPV + 2-doses bOPV (Liquid)

Experimental group

Description:

sIPV: Inactivated Poliomyelitis Vaccine Made from Sabin Strains Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 0.5ml/dose bOPV (Liquid): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 0.5ml or 1.0ml each bottle;total content of polio virus≥7.12lgCCID50/ml，type1 polio virus≥7.0 lgCCID50/ml，type 3 polio virus ≥6.5lgCCID50/ml.(2 drops per person;be be equivalent to 0.1ml each person )

Treatment:

Biological: 1-dose sIPV + 2-doses bOPV (Liquid)

2-doses cIPV + 1-dose bOPV (Liquid)

Experimental group

Description:

cIPV: Inactivated Poliomyelitis Vaccine Made from Wild Polio Strains Produced by Sanofi Pasteur Co., Ltd. 0.5ml/dose bOPV (Liquid): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 0.5ml or 1.0ml each bottle;total content of polio virus≥7.12lgCCID50/ml，type1 polio virus≥7.0 lgCCID50/ml，type 3 polio virus ≥6.5lgCCID50/ml.(2 drops per person;be be equivalent to 0.1ml each person )

Treatment:

Biological: 2-doses cIPV + 1-dose bOPV (Liquid)

2-doses sIPV + 1-dose bOPV (Liquid)

Experimental group

Description:

sIPV: Inactivated Poliomyelitis Vaccine Made from Sabin Strains Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 0.5ml/dose bOPV (Liquid): bivalent oral attenuated live poliomyelitis vaccine against type 1 and type 3 (Human Diploid Cell) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 0.5ml or 1.0ml each bottle,total content of polio virus≥7.12lgCCID50/ml，type1 polio virus≥7.0 lgCCID50/ml，type 3 polio virus ≥6.5lgCCID50/ml.(2 drops per person;be be equivalent to 0.1ml each person )

Treatment:

Biological: 2-doses sIPV + 1-dose bOPV (Liquid)

2-doses cIPV + 1-dose tOPV (Liquid)

Experimental group

Description:

cIPV: Inactivated Poliomyelitis Vaccine Made from Wild Polio Strains Produced by Sanofi Pasteur Co., Ltd. 0.5ml/dose tOPV(Liquid) Trivalent oral attenuated live poliomyelitis vaccine against type 1, type 2 and type 3 in Dragee Candy (Vero) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 1.0ml each bottle,total content of polio virus≥7.15lgCCID50/ml，type1 polio virus≥ 7.0 lgCCID50/ml，type2 polio virus ≥ 6.0lgCCID50/ml，type 3 polio virus≥ 6.5lgCCID50/ml.(2 drops per person;be be equivalent to 0.1ml each person )

Treatment:

Biological: 2-doses cIPV + 1-dose tOPV (Liquid)

2-doses sIPV + 1-dose tOPV (Liquid)

Experimental group

Description:

sIPV: Inactivated Poliomyelitis Vaccine Made from Sabin Strains Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences.0.5ml/dose Trivalent oral attenuated live poliomyelitis vaccine against type 1, type 2 and type 3 in Dragee Candy (vero) Produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. 1.0ml each bottle,total content of polio virus≥7.15lgCCID50/ml，type1 polio virus≥7.0 lgCCID50/ml，type 2 polio virus ≥ 6.0lgCCID50/ml，type 3 polio virus ≥ 6.5lgCCID50/ml.(2 drops per person;be be equivalent to 0.1ml each person )

Treatment:

Biological: 2-doses sIPV + 1-dose tOPV (Liquid)