Safety and Immunogenicity of Oral Cholera Vaccine in Kolkata

Safety and Immunogenicity of a Killed, Oral Cholera Vaccine in Indian Subjects in Eastern Kolkata, West Bengal

The purpose of the study is to confirm the safety and immunogenicity of the oral killed bivalent cholera vaccine in adult and pediatric volunteers in Eastern Kolkata, West Bengal, India.

Study Overview

• Status: Completed
• Conditions: Cholera
• Intervention / Treatment: Biological: killed whole cell oral cholera vaccine; Biological: Heat Killed E. coli

Detailed Description

Cholera remains to be a serious public health problem worldwide. In the mid-1980s following technology transfer from Sweden, Vietnamese scientists developed and produced an oral killed monovalent cholera vaccine for Vietnam's public health programs. A 2-dose regimen of this vaccine has been shown to be safe and efficacious. Subsequently, a bivalent vaccine was developed containing the newly emergent O139 V. cholerae. This vaccine has several advantages over the existing Swedish vaccine. It confers protection against the El Tor biotype in younger children, is considerably less expensive, does not require a buffer during administration and does not require strict cold chain requirements. However, this vaccine is not licensed for use in countries other than Vietnam.

Through IVI, an agreement between VABIOTECH in Hanoi and Shantha Biotechnics PVT, LTD in India has been reached that will make the bivalent vaccine available in India. A double-blind randomized phase III trial in a cholera-endemic area would be necessary to demonstrate the efficacy of this vaccine in other settings. This would pave the way for the introduction of the vaccine into the national immunization programme in India and the internationalization of this vaccine and licensure in other countries where it is needed. Prior to the phase III trial, a phase II study will be performed among adults and children.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • West Bengal
    • Kolkata, West Bengal, India
      • National Institute of Cholera and Enteric Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 40 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy non-pregnant adults aged 18-40 years and children aged 1-17 years

Exclusion Criteria:

• Diarrhea during the past week
• Antibiotic and anti-diarrheal medicine use during the past week
• One or more episodes of diarrhea or abdominal pain lasting for 2 weeks during the past 6 months
• Abdominal pain, nausea, vomiting, loss of appetite or generalized ill feeling for the past 24 hours
• Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Killed Whole Cell Oral Cholera Vaccine	Biological: killed whole cell oral cholera vaccine; Bivalent oral killed cholera vaccine: each dose of this vaccine contains: Inactivated V.Cholerae Inaba (569B), Classical biotype - 25.109 cells; Inactivated V.Cholerae Ogawa (Cairo 50) Classical biotype - 25.109 cells; Inactivated V.Cholerae Inaba (Phil 6973) El Tor biotype - 50.109 cells; Inactivated V.Cholerae O139 - 50.109 cells each 1.5 mL dose given orally, two doses given 14 days apart
Placebo Comparator: 2; Heat-killed E. coli	Biological: Heat Killed E. coli; Escherichia coli K12 strain placebo: each dose of placebo contains heat-killed E. coli K12 strain in an amount whose optical turbidity is identical to that for the cholera vaccine. Each 1.5 mL dose given orally, two doses given 14 days apart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
adverse events	immediate events - 30 minutes after each dose, adverse events - for 3 days following dose, serious adverse events throughout study - 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
serum vibriocidal antibody response	baseline and 14 days after second dose

Collaborators and Investigators

• Sponsor: International Vaccine Institute
• Collaborators: Indian Council of Medical Research; National Institute of Cholera and Enteric Diseases, India; Shantha Biotechnics Limited
• Investigators: Principal Investigator: Sujit K Bhatttacharya, MD, National Institute of Cholera and Enteric Diseases, India

Publications and helpful links

General Publications

• Mahalanabis D, Lopez AL, Sur D, Deen J, Manna B, Kanungo S, von Seidlein L, Carbis R, Han SH, Shin SH, Attridge S, Rao R, Holmgren J, Clemens J, Bhattacharya SK. A randomized, placebo-controlled trial of the bivalent killed, whole-cell, oral cholera vaccine in adults and children in a cholera endemic area in Kolkata, India. PLoS One. 2008 Jun 4;3(6):e2323. doi: 10.1371/journal.pone.0002323.

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): July 1, 2006

Study Registration Dates

• First Submitted: July 4, 2005
• First Submitted That Met QC Criteria: July 4, 2005
• First Posted (Estimate): July 13, 2005

Study Record Updates

• Last Update Posted (Estimate): July 4, 2008
• Last Update Submitted That Met QC Criteria: June 26, 2008
• Last Verified: June 1, 2008

More Information

Terms related to this study

• Keywords: watery diarrhea; cholera vaccine
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vibrio Infections; Cholera
• Other Study ID Numbers: C-8-ph2