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

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

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.

Study Overview

• Status: Completed
• Conditions: Typhoid Fever
• Intervention / Treatment: Biological: Vi-CRM197 vaccine; Biological: Pneumococcal conjugate vaccine; Biological: Vi Polysaccharide (PS) vaccine

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Philippines
  • Alabang, Muntinlupa City, Philippines, 1781
    • Research Institute for Tropical Medicine (RITM)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Novartis
• Investigators: Principal Investigator: Maria Rosario Z Capeding, MD, Research Institute for Tropical Medicine (RITM)

Publications and helpful links

General Publications

• Bhutta ZA, Capeding MR, Bavdekar A, Marchetti E, Ariff S, Soofi SB, Anemona A, Habib MA, Alberto E, Juvekar S, Khan RM, Marhaba R, Ali N, Malubay N, Kawade A, Saul A, Martin LB, Podda A. Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: results from two randomised, observer-blind, age de-escalation, phase 2 trials. Lancet Infect Dis. 2014 Feb;14(2):119-29. doi: 10.1016/S1473-3099(13)70241-X. Epub 2013 Nov 28.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: September 19, 2011
• First Submitted That Met QC Criteria: September 19, 2011
• First Posted (Estimate): September 20, 2011

Study Record Updates

• Last Update Posted (Estimate): April 10, 2014
• Last Update Submitted That Met QC Criteria: March 5, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Salmonella Infections; Typhoid Fever; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: H01_05TP