Clinical trial NCT03614702: Clinic Trial to Evaluate the Safety and Immunogenicity by Different Sequential Schedules of bOPV and IPV
Official title: Safety and Immunogenicity Evaluation of Different Sequential Immunization Schedules of Type1+2 Bivalent Oral Poliovirus Vaccine(bOPV) Co-administered With Inactived Poliovirus Vaccine(IPV) in Infants Aged 2 Months: a Randomized, Double Blind, Single Center, Parallel Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Poliomyelitis
Keywords: bOPV
IPV
sequential immunization
immunogenecity
safety
Lead sponsor: Institute of Medical Biology, Chinese Academy of Medical Sciences
Sponsor class: OTHER
Collaborators: name: Guangxi Center for Disease Control and Prevention
First posted: 2018-08-03
Enrollment: 1200
Sex: ALL
Minimum age (years): 2
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Antibody titers of anti-poliovirus antibodies in serum of children who received 2 -doses cIPV/sIPV+1 dose tOPV or 2-doses cIPV/sIPV +1 dose bOPV.
timeFrame: at the 28 days after finishing the 3rd dose
Secondary outcomes:
measure: Safety:number of adverse events and serious adverse events
timeFrame: within 28 days after each dose injection
measure: Long term Safety:number of serious adverse events
timeFrame: Up to 6month after finishing the 3rd dose
measure: Antibody titers of anti-poliovirus antibodies in serum of children who received 1 dose cIPV/sIPV+2 dose bOPV(candy/liquid) or 2 doses cIPV/sIPV+1 dose bOPV
timeFrame: at the 28 days after finishing the 3rd dose
Other outcomes:
measure: Viral shedding
timeFrame: before the second dose;the 7 days after the second dose;the 14 days after the second dose;the 28 days after the second dose;the 7 days after the third dose;the 14 days after the third dose;the 28 days after the third dose
Locations:
city: Nanning
country: China
facility: Guangxi Provincial Center for Diseases Control and Prevention
state: Guangxi
Study officials:
affiliation: Guangxi Province Center for Diseases Control and Prevention
name: Zhaojun Mo, Master
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen S, Zhao Y, Yang Z, Li Y, Shi H, Zhao T, Yang X, Li J, Li G, Wang J, Ying Z, Yang J. The impact of different IPV-OPV sequential immunization programs on hepatitis A and hepatitis B vaccine efficacy. Hum Vaccin Immunother. 2022 Dec 31;18(1):2024063. doi: 10.1080/21645515.2021.2024063. Epub 2022 Jan 19.