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

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

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.

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): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Maharastra
    • Pune, Maharastra, India, 411011
      • K.E.M. Hospital Research Centre
• Pakistan
  • Karachi, Pakistan, 74800
    • The Aga Khan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 45 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

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
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
Experimental: Vi-CRM, Adults; Adults (18 to 45 years) receiving 1 dose of NVGH Vi-CRM197 vaccine	Biological: Vi-CRM197 vaccine
Active Comparator: Vi-PS, Adults; Adults (18 to 45 years) receiving 1 dose of licensed Vi Polysaccharide vaccine	Biological: Vi Polysaccharide (PS) vaccine; Other Names: Typherix
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

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: 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

Collaborators and Investigators

• Sponsor: Novartis
• Investigators: Study Director: NVGH, Novartis

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: March 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: October 25, 2010
• First Submitted That Met QC Criteria: October 26, 2010
• First Posted (Estimate): October 27, 2010

Study Record Updates

• Last Update Posted (Estimate): May 1, 2014
• Last Update Submitted That Met QC Criteria: April 11, 2014
• Last Verified: April 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_02TP