The Clinical Trial Protocol for the Inactivated Poliomyelitis Vaccine Made From Sabin Strains(Sabin IPV)

Study Overview
=================
Brief Summary
-----------------
Based on pre-clinical trial and phase 1 and phase 2 clinical data and principle of GCP, the objective of phase Ⅲ clinical trial is to evaluate safety and immunogenicity of Inactivated Poliomyelitis Vaccine made from Sabin Strains(Sabin IPV).

Detailed Description
-----------------
The Sabin IPV was manufactured with poliovirus type 1, 2, 3 Sabin strains and Vero cells by microcarrier culture in 550 liter bioreactors. The virus suspension was harvested, ultra-concentrated, purified and inactivated with formalin. The D Ag contents of Sabin IPV were type 1 30DU, type 2 32DU, type 3 45DU /0.5ml/per dose. Inactivated Poliomyelitis Vaccine (Salk strains) was manufactured by Sanofi Pasteur D Ag contents /0.5ml/per dose were type 1 40DU, type 2 8DU, type 3 32DU. This is a randomized, blind phase 3 clinical trial. Total 1200 infants (ages 60 days to 90 days) were selected, randomized to two groups (Sabin IPV and Salk IPV, each group n=600), infants in each group will be vaccinated with three doses of either Sabin IPV or Salk IPV respectively, one month apart.

Official Title
-----------------
The Phase Ⅲ Clinical Trial Protocol for the Inactivated Poliomyelitis Vaccine Made From Sabin Strains

Conditions
-----------------
Poliomyelitis

Intervention / Treatment
-----------------
* Biological: Inactivated Poliomyelitis Vaccine (Sabin strains)
* Biological: Inactivated Poliomyelitis Vaccine (Salk strains)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females, age from 60 days to 90 days; Adults, 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; Infants no vaccinated with poliovaccine or other preventive biologicals in recent 7 days; Axillary temperature ≤37℃. Exclusion Criteria: Have medical record of participants or their family on allergy, convulsion, falling sickness, encephalopathy and psychopathy; Low platelet or bleeding disorder do not allow vaccination into the muscle; Have damaged or lower immunological function; Received blood, plasma or immunoglobulin treatment since birth; Have inborn abnormality, develop obstacles or clinical diagnostic serious chronic ( Down Syndrome, diabetes, sickle cell anemia or neural Guillain-Barre Syndrome ); Have or be doubtful of following diseases: respiratory system diseases, acute infection or active chronic, cardiovascular diseases, liver and kidney diseases, skin diseases, HIV. Exclusion Criteria for doses 2 and 3 Have serious anaphylaxis or high fever, convulsion during first dose; Have any circus of Exclusion Criteria after Eligible for study; Have serious adverse event which related to previous vaccination; Withdrawal and Discontinuance Criteria; Received necessary or interference study drugs such as: immune-inhibition or immune-stimulating agents; Vaccinated with any other vaccine（except DTP）; Stop observation determined by investigator owing to occurring serious adverse event.

Ages Eligible for Study
-----------------
Minimum Age: 60 Days
Maximum Age: 90 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Inactivated Poliomyelitis Vaccine (Sabin strains) 3 x 0.5ml intramuscular injections. | Biological: Inactivated Poliomyelitis Vaccine (Sabin strains)<br>* Inactivated Poliomyelitis Vaccine (Sabin strains) 3 x 0.5ml intramuscular injections, one month apart.<br>* Other names: Sabin IPV;|
| Experimental: Cohort 2:<br>Inactivated Poliomyelitis Vaccine (Salk strains) 3 x 0.5ml intramuscular injections. | Biological: Inactivated Poliomyelitis Vaccine (Salk strains)<br>* Inactivated Poliomyelitis Vaccine (Salk strains)3 x 0.5ml intramuscular injections, one month apart.<br>* Other names: Salk IPV or cIPV;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The study on immunogenicity of Inactivated Poliomyelitis Vaccine made from Sabin Strains on Healthy infants | Parallel study on comparison of sera protection rates (Neutralization antibody titer ≥1:8) of Sabin IPV and Salk IPV after three doses of vaccination. | fours year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The study on efficacy of Inactivated Poliomyelitis Vaccine made from Sabin Strains on Healthy infants | Comparison of geometric mean titers (GMTs) of Sabin IPV and Salk IPV after three doses of vaccination | One year | 
| Mucosal Immunity - Comparison of intestinal excretion of polioviruses following one dose of tOPV after three doses of IPV | One dose of tOPV was given after one month of third dose of IPV. The stool specimens were obtained at 0, 7, 14, 21, 28 days after OPV challenge. And determine the excretion rates of polioviruses. | 30-60 days after third dose immunization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inactivated Poliomyelitis Vaccine, Sabin Strains, poliomyelitis