Evaluation of Safety and Immunogenicity of Inactivated Adjuvanted Polio Vaccine in Comparison With Licensed Inactivated Poliovirus Vaccine

Study Overview
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Brief Summary
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This Phase III study has been designed to compare the SII Inactivated Salk Polio Vaccine (Adsorbed) with Sii licensed IPV by testing the vaccine in infants (three doses administered 4 weeks apart, starting at 6-8 weeks of age) in order to demonstrate the non-inferiority in the induction of specific poliovirus neutralizing antibody (PVNA) to poliovirus type 1, type 2 and type 3 by these vaccines. The study will also evaluate lot-to-lot consistency in the manufacture of SII Inactivated Salk Polio Vaccine (Adsorbed) by demonstrating equivalence in the induction of PVNA across three production lots.

Detailed Description
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The study is designed as a double-blind, randomized, active-controlled Phase III study with four groups of infants (n=268 per group) receiving either SII Inactivated Salk Polio Vaccine (Adsorbed) from the three lots or Sii licensed IPV. Participants will be screened for eligibility with their parental consent and will be selected for the study according to inclusion and exclusion criteria. A total of 1072 participants will be enrolled. Following vaccination, enrolled participants will remain in the clinic for at least 30 minutes for observation. During this time, they will be closely monitored for any immediate adverse events. Safety will be evaluated by active surveillance for solicited adverse events over the 4-day period after each vaccination in all participants. In addition, surveillance for unsolicited AEs and SAEs will be carried out over the period from first vaccination and 28 days after the third vaccination in all participants. The immunogenicity will be assessed by measuring the PVNA to poliovirus type 1, type 2 and type 3 using a standardized microneutralization test in the sera samples of the participants.

Official Title
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A Phase III, Double Blind, Randomized, Active Controlled Study to Evaluate Safety and Immunogenicity of Inactivated Adjuvanted Polio Vaccine in Comparison With Licensed Inactivated Poliovirus Vaccine

Conditions
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Poliomyelitis

Intervention / Treatment
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* Biological: SII Inactivated Salk Polio Vaccine (Adsorbed) - Lot A
* Biological: SII Inactivated Salk Polio Vaccine (Adsorbed) - Lot B
* Biological: SII Inactivated Salk Polio Vaccine (Adsorbed) - Lot C
* Biological: Sii Licensed IPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infants as established by medical history and clinical examination before entering the study Age: 6-8 weeks at the time of enrolment Parental ability and willingness to provide informed consent Parent who intends to reside in the area with the infant during the study period Exclusion Criteria: Presence of fever on the day of enrolment [Temporary exclusion criteria]. Acute disease at the time of enrolment [Temporary exclusion criteria]. Prior receipt or intent to receive OPV/IPV/IPV containing vaccines during the study period. OPV vaccination or known exposure to poliovirus (wild or vaccine derived) in household (living together) within 3-months prior to inclusion or planned during the study. Presence of significant malnutrition (weight-for-height z-score < -3SD median) Known or suspected impairment of immunological function based on medical history and physical examination. Presence of any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer, or autoimmune disease) as determined by medical history and / or physical examination which would compromise the participant's health or is likely to result in nonconformance to the protocol. A known sensitivity or allergy to any components of the Investigational Product. Receipt of immunoglobulin therapy and / or blood products since birth or planned administration during the study period Planned concurrent participation in another clinical study at any point throughout the entire study period

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 8 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Study participants aged 6 to 8 weeks will be enrolled and randomized into 1:1:1:1 ratio to receive either the SII inactivated Salk polio vaccine (adsorbed) from one of the three lots (Lot A or Lot B or Lot C) or the Sii licensed inactivated poliovirus vaccine (IPV).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SII Inactivated Salk Polio Vaccine (Adsorbed) Lot A<br>SII Inactivated Salk Polio Vaccine (Adsorbed) Lot A | Biological: SII Inactivated Salk Polio Vaccine (Adsorbed) - Lot A<br>* SII Inactivated Salk Polio Vaccine (Adsorbed) produced by Serum Institute of India Pvt. Ltd., is a sterile suspension of three types of inactivated poliovirus: Type 1 (Mahoney), Type 2 (MEF-1), and Type 3 (Saukett). It is a highly purified, adjuvanted reduced antigen content of inactivated poliovirus vaccine.<br>|
| Experimental: SII Inactivated Salk Polio Vaccine (Adsorbed) Lot B<br>SII Inactivated Salk Polio Vaccine (Adsorbed) Lot B | Biological: SII Inactivated Salk Polio Vaccine (Adsorbed) - Lot B<br>* SII Inactivated Salk Polio Vaccine (Adsorbed) produced by Serum Institute of India Pvt. Ltd., is a sterile suspension of three types of inactivated poliovirus: Type 1 (Mahoney), Type 2 (MEF-1), and Type 3 (Saukett). It is a highly purified, adjuvanted reduced antigen content of inactivated poliovirus vaccine.<br>|
| Experimental: SII Inactivated Salk Polio Vaccine (Adsorbed) Lot C<br>SII Inactivated Salk Polio Vaccine (Adsorbed) Lot C | Biological: SII Inactivated Salk Polio Vaccine (Adsorbed) - Lot C<br>* SII Inactivated Salk Polio Vaccine (Adsorbed) produced by Serum Institute of India Pvt. Ltd., is a sterile suspension of three types of inactivated poliovirus: Type 1 (Mahoney), Type 2 (MEF-1), and Type 3 (Saukett). It is a highly purified, adjuvanted reduced antigen content of inactivated poliovirus vaccine.<br>|
| Active Comparator: Sii Licensed IPV<br>Sii Licensed IPV | Biological: Sii Licensed IPV<br>* Poliomyelitis Vaccine (Inactivated), produced by Serum Institute of India Pvt. Ltd., is a sterile suspension of three types of inactivated poliovirus: Type 1 (Mahoney), Type 2 (MEF-1), and Type 3 (Saukett). Poliomyelitis Vaccine (Inactivated) is a highly purified, inactivated poliovirus vaccine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with type-specific seroconversion | Percentage of participants with type-specific seroconversion* on Day 28 after the third vaccination for SII Inactivated Salk Polio Vaccine (Adsorbed) and Sii Licensed IPV | Day 28 after third vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers | Type-specific geometric mean titers on day 28 after the third vaccination of three cGMP lots of SII Inactivated Salk Polio Vaccine (Adsorbed) and Sii Licensed IPV. | Day 28 after third vaccination | 
| Reverse cumulative distribution curves of antibody titers | Type-specific reverse cumulative distribution curves of antibody titers on pre-vaccination and 28 days after third vaccination of three cGMP lots of SII Inactivated Salk Polio Vaccine (Adsorbed) and Sii Licensed IPV. | pre-vaccination and 28 days after third vaccination | 
| Percentage of participants with type-specific seroprotection | Percentage of participants with type-specific seroprotection (titers ≥ 8) on Day 28 after the third vaccination of three cGMP lots of SII Inactivated Salk Polio Vaccine (Adsorbed) and Sii Licensed IPV. | Day 28 after the third vaccination | 
| Percentage of participants with type-specific post-vaccination titers ≥ 4-fold above the estimated titer of maternal antibody | Percentage of participants with type-specific post-vaccination titers ≥ 4-fold above the estimated titer of maternal antibody on day 28 after the third vaccination of three cGMP lots of SII Inactivated Salk Polio Vaccine (Adsorbed) and Sii Licensed IPV. | Day 28 after the third vaccination |