Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Children, Older Infants and Infants

Study Overview
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Brief Summary
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This phase 2 trial is aimed to obtain information on the safety and immunogenicity of the Vi-CRM197 in children and infants from various age groups in the Philippines where Typhoid Fever is highly endemic and an efficacious vaccine against this disease is very much needed.

Official Title
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A Phase 2, Randomized, Controlled, Observer Blind, Single Center Study of the Safety, Reactogenicity and Immunogenicity of the NVGH Glycoconjugate Vaccine Against S. Typhi in Children, Older Infants and Infants

Conditions
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Typhoid Fever

Intervention / Treatment
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* Biological: Vi-CRM197 vaccine
* Biological: Pneumococcal conjugate vaccine
* Biological: Vi Polysaccharide (PS) vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects belonging to 3 age groups will be enrolled into the trial: children (24 to 59 months of age at enrollment), older infants (9 to 12 months of age at enrollment) and infants (6 weeks of age at enrolment). Written informed consent will be obtained by the parents/ guardians before enrollment into the trial. Infants who have been vaccinated with BCG and HBV at birth and OPV at any time since birth can be enrolled into the trial, while infants who have received DTwP+HBV+Hib due at 6 weeks of age as per local EPI schedule cannot be enrolled into the trial.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 59 Months

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vi-CRM, Older infants<br>Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine | Biological: Vi-CRM197 vaccine<br> <br> |
| Active Comparator: PNC13, Older infants<br>Older infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine | Biological: Pneumococcal conjugate vaccine<br> <br> * Other names: Prevenar 13;|
| Experimental: Vi-CRM, Infants<br>Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine | Biological: Vi-CRM197 vaccine<br> <br> |
| Active Comparator: PNC13, Infants<br>Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine | Biological: Pneumococcal conjugate vaccine<br> <br> * Other names: Prevenar 13;|
| Experimental: Vi-CRM, Children<br>Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine | Biological: Vi-CRM197 vaccine<br> <br> |
| Active Comparator: Vi-PS, Children<br>Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine | Biological: Pneumococcal conjugate vaccine<br> <br> * Other names: Prevenar 13;Biological: Vi Polysaccharide (PS) vaccine<br> <br> * Other names: Typherix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer |  | At 28 days after last vaccination as compared to baseline | 
| Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer |  | At 6 months after last vaccination as compared to baseline | 
| Anti-Vi ELISA Geometric Mean Concentration (GMC) |  | At 28 days after last vaccination | 
| Anti-Vi ELISA GMC |  | At 6 months after last vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination | Solicited local reactions were: erythema, induration, pain/tenderness. Solicited systemic reactions were; lethargy, irritability, vomiting, diarrhoea, loss of appetite (and persistent crying in the older infants and infants age group) | During the 7-day follow-up period after vaccination |