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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 HepA-L or HepA-I in children aged 18 months. The primary immunogenicity endpoints in all groups are the seroconversion rates of type I, II, and III anti-poliovirus neutralizing antibodies and the seroconversion rate of anti-hepatitis A virus antibodies 30 days after the final administration. The secondary immunogenicity endpoints are (1) the GMT/GMC of type I, II, and III anti-poliovirus neutralizing antibodies as well as the anti-hepatitis A virus antibodies 30 days after the final administration; (2) the seropositive rates of the anti-hepatitis A virus antibodies 30 days after the final administration; (3) the GMFI of type I, II, and III anti-poliovirus neutralizing antibodies as well as the anti-hepatitis A virus antibodies 30 days after the final administration. 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 HepA-L or HepA-I. 2000 children subjects aged 4 months will be enrolled to take administration of 1 dose of sIPV. All participants at 18 months of age will be randomly assigned to 5 cohorts in a ratio of 4:4:4:3:3, that is, (1) 400 subjects will be concomitantly injected with sIPV and HepA-L, (2) 400 subjects will be concomitantly injected with sIPV and HepA-I, and another dose of HepA-I at 24 months of age (3) 400 subjects will be only injected one dose of sIPV, (4) 300 subjects will be only injected with one dose of HepA-L, (5) 300 subjects will be only injected with two doses of HepA-I at 18 and 24 months of age, respectively.
For safety assessment, adverse events after the third dose of sIPV at 4 months of age would be collected through phone-call follow-ups on Day 8 and Day 30 after the injection by investigators and active reports from participants' guardians. At 18 months of age, safety data 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.
For immunogenicity assessment, blood samples before each dose on Day 0 and Day 30 after each injection would be collected to evaluate the type I, II, and III anti-poliovirus neutralizing antibody levels or/and anti-hepatitis A virus antibody for different groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| sIPV + HepA-L (coconmitant vaccination cohort) | Experimental | Concomitant administration of sIPV and HepA-L at 18 months of age |
|
| sIPV + HepA-I (coconmitant vaccination cohort) | Experimental | Concomitant administration of sIPV and HepA-I at 18 months of age, and another dose administration of HepA-I at 24 months of age |
|
| sIPV (individual vaccination cohort) | Experimental | One booster dose of sIPV at 18 months of age |
|
| HepA-L (individual vaccination cohort) | Experimental | One dose of Hep-L at 18 months of age |
|
| HepA-I (individual vaccination cohort) | Experimental | Two doses of Hep-I at 18 and 24 months of age, respectively |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sIPV (booster dose at 18 months of age) | Biological | Sabin-strain-based inactivated vaccine (Vero cells), 0.5mL for each dose at 18 months of age for the booster one |
|
| 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 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 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 vaccination |
| Immunogenicity index-seropositive rate of type I anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. Seroconversion will be defined as the level (≥1:8). | Day 30 after vaccination |
| Immunogenicity index-seropositive rate of type II anti-poliovirus neutrilizing antibody | Neutralizing antibody assay will be performed using the neutralization method. Seroconversion will be defined as the level (≥1:8). | Day 30 after vaccination |
| Immunogenicity index-seropositive rate of type III anti-poliovirus neutrilizing antibody |
| Measure | Description | Time Frame |
|---|---|---|
| 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 vaccination |
| Immunogenicity index-geometric mean titer (GMT) of type II 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 |
|---|---|---|
| Jiawei Xu | Chongqing Center for Disease Control and Prevention | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jiu Longpo District Center for Disease Control and Disease | Chongqing | Chongqing Municipality | China |
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| ID | Term |
|---|---|
| D011051 | Poliomyelitis |
| D006506 | Hepatitis A |
| ID | Term |
|---|---|
| D009187 | Myelitis |
| D002494 | Central Nervous System Infections |
| D007239 | Infections |
| D004769 | Enterovirus Infections |
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| ID | Term |
|---|---|
| D000375 | Aging |
| ID | Term |
|---|---|
| D048788 | Growth and Development |
| D010829 | Physiological Phenomena |
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| HepA-L | Biological | Freeze-dried/lyophilized live-attenuated hepatitis A virus vaccine, 1.0mL for each dose at 18 months of age |
|
| HepA-I | Biological | Inactivated hepatitis A virus vaccine, 0.5mL for each dose, two doses at 18 and 24 months of age, respectively |
|
Neutralizing antibody assay will be performed using the neutralization method. Seroconversion will be defined as the level (≥1:8). |
| Day 30 after vaccination |
| Immunogenicity index-seroconversion rate of anti-hepatitis A virus antibody | Antibody assay will be performed using the ELISA method. Seroconversion will be defined as a change from seronegative (<20mIU/ml) to seropositive (≥20mIU/ml), or a ≥4-fold increase from baseline | Between baseline and day 30 after vaccination |
Neutralizing antibody assay will be performed using the neutralization method. |
| Day 30 after 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 vaccination |
| Immunogenicity index-geometric mean concentration (GMC) of anti-hepatitis A virus antibody | Antibody assay will be performed using the ELISA method. | Day 30 after vaccination |
| Immunogenicity index-seropositive rate of anti-hepatitis A virus antibody | Antibody assay will be performed using the ELISA method. Seropositive will be defined as the level (≥20mIU/ml). | Day 30 after 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 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 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 vaccination |
| Immunogenicity index-geometric mean fold increase (GMFI) of anti-hepatitis A 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 solicited 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 unsolicited adverse events | Incidence of unsolicited adverse events after vaccination | Day 0-30 after vaccination |
| Safety index-incidence of adverse events | Incidence of 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 |
| Wanzhou District Center for DIsease Control and Prevention | Chongqing | Chongqing Municipality | China |
|
| Jiangjin District Center for Disease Control and Prevention | Chongqing | Chonqing | 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 |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |