Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Adults, 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 subjects from various age groups in India and Pakistan 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 2a, Randomized, Controlled, Observer Blind, Age De-Escalation, Multicenter and Multinational Study of the Safety, Reactogenicity and Immunogenicity of the NVGH Glycoconjugate Vaccine Against S. Typhi in Adults, Children, Older Infants and Infants

Conditions
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Typhoid Fever

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


Participation Criteria
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Eligibility Criteria
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Main eligibility criteria: Subjects belonging to 4 age groups will be enrolled into the trial: adults (18 to 45 years of age), children (24 to 59 months of age), 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 all subjects or their parents/ guardians (depending on the age group) before enrollment into the trial. Only females with a negative pregnancy test and willing to participate in family planning consultations (organized by the site study team) will be allowed to participate to the trial. Infants who have been vaccinated with 1 dose of BCG, HBV and OPV at birth can be enrolled into the trial, while infants who have received DTwP+HBV+Hib or OPV 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: 45 Years

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vi-CRM, Adults<br>Adults (18 to 45 years) receiving 1 dose of NVGH Vi-CRM197 vaccine | Biological: Vi-CRM197 vaccine<br> <br> |
| Active Comparator: Vi-PS, Adults<br>Adults (18 to 45 years) receiving 1 dose of licensed Vi Polysaccharide vaccine | Biological: Vi Polysaccharide (PS) vaccine<br> <br> * Other names: Typherix;|
| 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: Vi Polysaccharide (PS) vaccine<br> <br> * Other names: Typherix;Biological: Pneumococcal conjugate vaccine<br> <br> * Other names: Prevenar 13;|
| 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;|

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: Adults, children, older infants, infants: erythema, induration and pain/tenderness at the injection site. Solicited systemic reactions were: Adults: chills, malaise, myalgia, arthralgia, headache, fatigue, rash and fever. Children, older infants and infants: lethargy, irritability, vomiting, diarrhoea, loss of appetite, rash and fever (and persistent crying in infants). | During the 7-day follow-up period after vaccination |