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This study is a randomized, open-labeled phase IV clinical trial to evaluate the immunogenicity and safety of concomitant administration of sIPV and DTaP or MMR in infants aged 2 months. Primary immunogenicity endpoints in all groups include the seroconversion rate of type I, II, and III anti-poliovirus neutralizing antibodies, anti-DT, anti-TT, anti-PT, anti-FHA, and anti-PRN antibodies 30 days after basic immunization. Secondary immunogenicity endpoints include the seropositive rates, seroconversion rates, geometric mean titer/concentration (GMT/GMC), geometric mean fold increase (GMFI) of type I, II, and III anti-poliovirus neutralizing antibodies, anti-DT, anti-TT, anti-PT, anti-FHA, and anti-PRN antibodies, and anti-measles, anti-mumps, and anti-rubella antibodies 30 days after full immunization. The secondary safety endpoints are the incidence of adverse events (AEs) within 30 minutes after each injection, the incidence of solicited local and systematic AEs in the period of solicitation after each injection, the incidence of unsolicited AEs in 30 days after each injection, the incidence of AEs in 30 days after each injection, and the incidence of serious adverse events in 6 months after administrations.
This is a randomized, open-labeled, parallel phase IV clinical trial to evaluate the immunogenicity and safety of concomitant administration of sIPV and DTaP or MMR. 2640 participants aged 2 months will be randomly assigned to 4 cohorts in a ratio of 1:1:1:1. [Cohort A] 660 infants will take administration of sIPV at 2, 3, 4, 18 months of age and DTaP at 2, 4, 6, and 18 months of age. sIPV and DTaP at 2, 4, and 18 months of age will be taken concomitantly. [Cohort B] 660 infants will take administration of sIPV at 2, 3 months of age, bOPV at 4 months and 4 years of age, and DTaP at 2, 4, 6, 18 months of age. sIPV/bOPV at 2, 4 months of age will be taken concomitantly. [Cohort C] 660 infants will take administration of sIPV at 2, 3, 4, 18 months of age, DTaP at 2, 4, 6, and 18 months of age, and MMR at 18 months of age. DTaP will be taken 7 days after sIPV at 2, 4, 18 months of age. Half participants will take concomitant administration of sIPV and MMR at 18 months of age, and the rest will take them separately (MMR at 19 months of age). [Cohort D] 660 infants will take administration of sIPV at 2, 3 months of age, bOPV at 4 months and 4 years of age, and DTaP at 2, 4, 6, 18 months of age. DTaP will be taken 7 days after sIPV/bOPV at 2, 4 months of age.
For immunogenicity assessment, blood samples on Day 0 and Day 30 after basic immunization of each kind of investigational vaccine would be collected to evaluate the type I, II, and III anti-poliovirus neutralizing antibodies, anti-DT, anti-TT, anti-PT, anti-FHA, and anti-PRN antibodies, and anti-measles, anti-mumps, and anti-rubella antibodies for different groups.
For safety assessment, adverse events after each dose would be recorded through the diary and contact cards by participants' guardians to collect solicited or unsolicited AEs in periods of solicitation and nonsolicitation, respectively. From 31 days after the final dose to 6 months later, serious adverse events will be evaluated by the investigator via phone call or active reports by participants' guardians.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| sIPV + DTaP (concomitant vaccination cohort) | Experimental | sIPV at 2,3,4 and 18 months of age, DTaP at 2,4,6 and 18 months of age |
|
| sIPV/bOPV + DTaP (concomitant vaccination cohort) | Experimental | sIPV at 2,3 months of age and bOPV at 4 months and 4 years of age DTaP at 2, 4, 6 and 18 months of age |
|
| sIPV + DTaP + MMR (systematic interval-based vaccination cohort) | Experimental | sIPV at 2,3,4 and 18 months of age DTaP at 2,4,6 and 18 months of age, 7 days after the administration of sIPV MMR at 18 months of age, randomly assigned in the concomitant administration with sIPV or 1 month after the administration of DTaP |
|
| sIPV/bOPV + DTaP (Systematic interval-based vaccination cohort) | Experimental | sIPV at 2,3 months of age, bOPV at 4 months and 4 years of age DTaP at 2,4,6 and 18 months of age, 7 days after the administration of sIPV |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sIPV | Biological | Sabin-strain-based inactivated vaccine (Vero cells), 0.5mL for each dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Immunogenicity index-seroconversion rate of type I anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. Seroconversion will be defined as a change from seronegative (<1:8) to seropositive (≥1:8), or a ≥4-fold increase from baseline | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-seroconversion rate of type II anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. Seroconversion will be defined as a change from seronegative (<1:8) to seropositive (≥1:8), or a ≥4-fold increase from baseline | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-seroconversion rate of type III anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. Seroconversion will be defined as a change from seronegative (<1:8) to seropositive (≥1:8), or a ≥4-fold increase from baseline | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-seroconversion rate of anti-DT antibody | Antibody assay will be performed using the ELISA method. Seroconversion will be defined as a change from seronegative (Antibody Concentration<0.1 IU/ml) to seropositive (Antibody Concentration≥0.1 IU/ml), or a ≥4-fold increase from baseline. | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-seroconversion rate of anti-TT antibody | Antibody assay will be performed using the ELISA method. Seroconversion will be defined as a change from seronegative (Antibody Concentration<0.1 IU/ml) to seropositive (Antibody Concentration≥0.1 IU/ml), or a ≥4-fold increase from baseline. |
| Measure | Description | Time Frame |
|---|---|---|
| Immunogenicity index-seropositive rate of type I anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. Seropositive will be defined as the antibody tie ≥1:8 | Day 30 after basic vaccination |
| Immunogenicity index-seropositive rate of type I anti-poliovirus neutrilizing antibody |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jingsi Yang | Contact | 0871-68334551 | +86 | yjs@imbcams.com.cn |
| Name | Affiliation | Role |
|---|---|---|
| Yan Zheng | Yunnan Provical Center for Disease Control and Prevention | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lufeng Center for Disease Control and Prevenion | Chuxiong | Yunnan | 651299 | China |
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| ID | Term |
|---|---|
| D011051 | Poliomyelitis |
| D013742 | Tetanus |
| D014917 | Whooping Cough |
| ID | Term |
|---|---|
| D009187 | Myelitis |
| D002494 | Central Nervous System Infections |
| D007239 | Infections |
| D004769 | Enterovirus Infections |
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| ID | Term |
|---|---|
| D022542 | Measles-Mumps-Rubella Vaccine |
| ID | Term |
|---|---|
| D017778 | Vaccines, Combined |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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| DTaP | Biological | Adsorbed acellular pertussis, diphtheria and tetanus combined vaccine, 0.5mL for each dose |
|
| bOPV 1,3 | Biological | Poliomyelitis Vaccine Type I Type Ⅲ in Dragee Candy (Human Diploid Cell), Live, 1g for each dose |
|
| MMR Vaccine | Biological | Measles, Mumps and Rubella Combined Live-attenuated Vaccine, 0.5mL for each dose |
|
| Between baseline and day 30 after basic vaccination |
| Immunogenicity index-seroconversion rate of anti-PT antibody | Antibody assay will be performed using the ELISA method. Seroconversion will be defined as a change from seronegative (Antibody Concentration<20 IU/ml) to seropositive (Antibody Concentration≥20 IU/ml), or a ≥4-fold increase from baseline. | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-seroconversion rate of anti-FHA antibody | Antibody assay will be performed using the ELISA method. Seroconversion will be defined as a change from seronegative (Antibody Concentration<20 IU/ml) to seropositive (Antibody Concentration≥20 IU/ml), or a ≥4-fold increase from baseline. | Between baseline and day 30 after basic vaccination |
Neutralizing antibody assay will be performed using the neutralization method. Seropositive will be defined as the antibody tie ≥1:8 |
| Day 30 after full vaccination |
| Immunogenicity index-seropositive rate of type II anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. Seropositive will be defined as the antibody tie ≥1:8 | Day 30 after basic vaccination |
| Immunogenicity index-seropositive rate of type II anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. Seropositive will be defined as the antibody tie ≥1:8 | Day 30 after full vaccination |
| Immunogenicity index-seropositive rate of type III anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. Seropositive will be defined as the antibody tie ≥1:8 | Day 30 after basic vaccination |
| Immunogenicity index-seropositive rate of type III anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. Seropositive will be defined as the antibody tie ≥1:8 | Day 30 after full vaccination |
| Immunogenicity index-geometric mean titer (GMT) of type I anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Day 30 after basic vaccination |
| Immunogenicity index-geometric mean titer (GMT) of type I anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Day 30 after full vaccination |
| Immunogenicity index-geometric mean titer (GMT) of type II anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Day 30 after basic vaccination |
| Immunogenicity index-geometric mean titer (GMT) of type II anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Day 30 after full vaccination |
| Immunogenicity index-geometric mean titer (GMT) of type III anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Day 30 after basic vaccination |
| Immunogenicity index-geometric mean titer (GMT) of type III anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Day 30 after full vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of type I anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of type I anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Between baseline and day 30 after full vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of type II anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of type II anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Between baseline and day 30 after full vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of type III anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of type III anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. | Between baseline and day 30 after full vaccination |
| Immunogenicity index-seropositive rate of anti-DT antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as the antibody concentration≥0.1 IU/ml. | Day 30 after basic vaccination |
| Immunogenicity index-seropositive rate of anti-DT antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as the antibody concentration≥0.1 IU/ml. | Day 30 after full vaccination |
| Immunogenicity index-seropositive rate of anti-TT antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as the antibody concentration≥0.1 IU/ml. | Day 30 after basic vaccination |
| Immunogenicity index-seropositive rate of anti-TT antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as the antibody concentration≥0.1 IU/ml. | Day 30 after full vaccination |
| Immunogenicity index-seropositive rate of anti-PT antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as the antibody concentration≥20 IU/ml. | Day 30 after basic vaccination |
| Immunogenicity index-seropositive rate of anti-PT antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as the antibody concentration≥20 IU/ml. | Day 30 after full vaccination |
| Immunogenicity index-seropositive rate of anti-FHA antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as the antibody concentration≥20 IU/ml. | Day 30 after basic vaccination |
| Immunogenicity index-seropositive rate of anti-FHA antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as the antibody concentration≥20 IU/ml. | Day 30 after full vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of antibody against DT | Antibody assay will be performed using the ELISA method | Day 30 after basic vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of antibody against DT | Antibody assay will be performed using the ELISA method | Day 30 after full vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of antibody against TT | Antibody assay will be performed using the ELISA method | Day 30 after basic vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of antibody against TT | Antibody assay will be performed using the ELISA method | Day 30 after full vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of antibody against PT | Antibody assay will be performed using the ELISA method | Day 30 after basic vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of antibody against PT | Antibody assay will be performed using the ELISA method | Day 30 after full vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of antibody against FHA | Antibody assay will be performed using the ELISA method | Day 30 after basic vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of antibody against FHA | Antibody assay will be performed using the ELISA method | Day 30 after full vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of antibody against DT | Antibody assay will be performed using the ELISA method | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of antibody against DT | Antibody assay will be performed using the ELISA method | Between baseline and day 30 after full vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of antibody against TT | Antibody assay will be performed using the ELISA method | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of antibody against TT | Antibody assay will be performed using the ELISA method | Between baseline and day 30 after full vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of antibody against PT | Antibody assay will be performed using the ELISA method | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of antibody against PT | Antibody assay will be performed using the ELISA method | Between baseline and day 30 after full vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of antibody against FHA | Antibody assay will be performed using the ELISA method | Between baseline and day 30 after basic vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of antibody against FHA | Antibody assay will be performed using the ELISA method | Between baseline and day 30 after full vaccination |
| Immunogenicity index-seroconversion rate of anti-measles virus antibody | Antibody assay will be performed using the ELISA method. Seroconversion will be defined as a change from seronegative (<200mIU/ml) to seropositive (≥200mIU/ml), or a ≥4-fold increase from baseline | Between baseline and day 30 after vaccination |
| Immunogenicity index-seroconversion rate of anti-rubella virus antibody | Antibody assay will be performed using the ELISA method. Seroconversion will be defined as a change from seronegative (<20IU/ml) to seropositive (≥20IU/ml), or a ≥4-fold increase from baseline | Between baseline and day 30 after vaccination |
| Immunogenicity index-seroconversion rate of anti-mumps virus antibody | Antibody assay will be performed using the ELISA method. Seroconversion will be defined as a change from seronegative (<100U/ml) to seropositive (≥100U/ml), or a ≥4-fold increase from baseline | Between baseline and day 30 after vaccination |
| Immunogenicity index-seropositive rate of anti-measles virus antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as antibody concentration ≥200mIU/ml | Day 30 after vaccination |
| Immunogenicity index-seropositive rate of anti-rubella virus antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as antibody concentration ≥20IU/ml | Day 30 after vaccination |
| Immunogenicity index-seropositive rate of anti-mumps virus antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as antibody concentration ≥100U/ml | Day 30 after vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of anti-measles virus antibody | Antibody assay will be performed using the ELISA method. | Day 30 after vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of anti-rubella virus antibody | Antibody assay will be performed using the ELISA method. | Day 30 after vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of anti-mumps virus antibody | Antibody assay will be performed using the ELISA method. | Day 30 after vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of anti-measles virus antibody | Antibody assay will be performed using the ELISA method. | Between baseline and day 30 after vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of anti-rubella virus antibody | Antibody assay will be performed using the ELISA method. | Between baseline and day 30 after vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of anti-mumps virus antibody | Antibody assay will be performed using the ELISA method. | Between baseline and day 30 after vaccination |
| Safety index-incidence of adverse events | Incidence of adverse events after vaccination | 0-30 minutes after vaccination |
| Safety index-incidence of solicitied adverse events | Incidence of solicited local and systematic adverse events after vaccination | Day 0-7 or Day 0-14 after vaccination |
| Safety index-incidence of unsolicitied adverse events | Incidence of unsolicited adverse events after vaccination | Day 0-30 after vaccination |
| Safety index-incidence of serious adverse events | Incidence of serious adverse events | From the beginning of the vaccination up to 6 months after vaccination completed |
| Yuanmou Center for Disease Control and Prevention | Chuxiong | Yunnan | 651300 | China |
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| Wuding Center for Disease Control and Prevention | Chuxiong | Yunnan | 651600 | China |
|
| Yaoan Center for Disease Control and Prevention | Chuxiong | Yunnan | 675300 | China |
|
| Lancang Center for Disease Control and Prevention | Puer | Yunnan | 665699 | China |
|
| Yanshan Center for Disease Control and Prevention | Wenshan | Yunnan | 663100 | China |
|
| Qiubei Center for Disease Control and Prevention | Wenshan | Yunnan | 663200 | China |
|
| Guangnan Center for Disease Control and Prevention | Wenshan | Yunnan | 663300 | China |
|
| Mile Center for Disease Control and Prevention | Yisa | Yunnan | 652399 | China |
|
| D010850 |
| Picornaviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D013118 | Spinal Cord Diseases |
| D000090862 | Neuroinflammatory Diseases |
| D009468 | Neuromuscular Diseases |
| D003015 | Clostridium Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D001885 | Bordetella Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D012141 | Respiratory Tract Infections |
| D012140 | Respiratory Tract Diseases |
| D008458 |
| Measles Vaccine |
| D014765 | Viral Vaccines |
| D009108 | Mumps Vaccine |
| D012411 | Rubella Vaccine |