Evaluation of a Boosting Regimen With Oral Cholera Vaccine (Boost)

A Open Labeled Controlled Trial to Evaluate the Immune Response of a Boosting Regimen With Shanchol™, a Killed Whole Cell Oral Cholera Vaccine (WC-OCV), in Previously Immunized Adults and Children in Eastern Kolkata, India

Data demonstrates that Shanchol™ (killed bivalent oral cholera vaccine) provides protection over 3 years and data regarding the protective efficacy over five years is anticipated for 2012. Regardless at the end of five years, it may still be necessary to provide a booster dose or reimmunize with two doses to maintain protection in previously immunized populations. This study examines the immune protection and safety of providing a one and two dose boosting regimen of Shanchol™ given five years after the initial dose.

Study Overview

• Status: Completed
• Conditions: Cholera
• Intervention / Treatment: Biological: Shanchol™, oral cholera vaccine; Biological: Shanchol™, killed, whole cell, bivalent, oral cholera vaccine; Other: no intervention

• Study Type: Interventional
• Enrollment (Actual): 426
• Phase: Phase 4

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: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All subjects must be presently enrolled in the Phase 3 NICED RCT of Shanchol™ and satisfy the following criteria at study entry:

1. Male or female adults aged 6 years and above, who are available for follow-up visits and specimen collection.

   • The subject should be able to continue in the study for the next 6 weeks
   • The subject (or parent/guardian) should be willing to provide 3 blood samples
2. Written informed consent obtained from the subjects or their parents/guardians, and written assent obtained from children aged 12 - 17 years.

3. Healthy subjects as determined by:

   • Medical history
   • Physical examination
   • Clinical judgment of the investigator

Exclusion Criteria:

1. individuals who are too weak to get out of bed to receive the vaccine
2. pregnant women (identified through verbal screening)
3. those less than 6 years of age
4. Receipt of cholera vaccine following 2009 (time of licensure and availability of Shanchol™ in India)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccine to past vaccinated participants; The first arm includes subjects, who were immunized with two Shanchol™ doses, five years prior. In this study, arm one will receive one Shanchol™ booster dose at baseline and one booster dose on day fourteen.	Biological: Shanchol™, oral cholera vaccine; This killed, whole cell, bivalent vaccine will be presented as a creamish white suspension. Upon storage, a white sediment and clear supernatant may be observed. The recommended dose (1.5ml) of the vaccine must be administered orally. The primary vaccination schedule consists of two doses given at an interval of two weeks. After vigorous shaking of the vial, 1.5 ml should be poured into the mouth of the recipient, followed by water ad libitum. The vaccine can alternatively be administered with a disposable syringe (without needle) after removing the contents from the vial and squirted into the mouth of the recipient. Vaccine is administered in 1.5 mL vials by mouth in 2 doses, given 2 weeks apart. The vaccine appears as a creamy white suspension.
Active Comparator: Vaccine to past placebo recipients; The second arm includes subjects, who received two placebo doses, five years prior. Arm two will receive a primary immunization series consisting of one Shanchol™ dose at baseline and one at day fourteen	Biological: Shanchol™, killed, whole cell, bivalent, oral cholera vaccine; This killed, whole cell, bivalent vaccine will be presented as a creamish white suspension. Upon storage, a white sediment and clear supernatant may be observed. The recommended dose (1.5ml) of the vaccine must be administered orally. The primary vaccination schedule consists of two doses given at an interval of two weeks. After vigorous shaking of the vial, 1.5 ml should be poured into the mouth of the recipient, followed by water ad libitum. The vaccine can alternatively be administered with a disposable syringe (without needle) after removing the contents from the vial and squirted into the mouth of the recipient. Vaccine is administered in 1.5 mL vials by mouth in 2 doses, given 2 weeks apart. The vaccine appears as a creamy white suspension.
Placebo Comparator: No intervention to past placebo recipients; The third arm includes subjects, who received two placebo doses, five years prior. This third arm will not receive any intervention and will serve to represent a baseline immune response by vaccine naïve individuals exposed to natural exposure.	Other: no intervention; No intervention will be given to this arm of past placebo recipients. To ensure that boosting was not due to natural exposure to Vibrio cholera, we will compare subjects in the boosting arm to this no intervention arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity provided by a two dose boosting regimen of Shanchol™	To determine whether two doses of Shanchol™ administered to a previously immunized cohort elicits similar immune responses (greater than fourfold rise in serum vibriocidal antibody titers through IgM) to those achieved by a primary immunization series in an unimmunized cohort stratified by age (6-14 and ≥15 years old),	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity provided by a one dose boosting regimen of Shanchol™	To determine if a one dose booster regimen of Shanchol™ administered to a previously immunized cohort can elicit similar immune responses (through serum IgM) to those achieved by primary immunization in an unimmunized cohort stratified by age (6-14 and ≥15 years old)	28 days
Rises in serum IgA and IgG following boosting regimens	Measure rises in serum IgA and IgG as an adjunct measure of immunogenic response to the Shanchol™ boosting regimens	28 days
Proportion of subjects with adverse events	To confirm the safety of one and two dose boosting regimens Shanchol™ in healthy, non-pregnant subjects stratified by age within 28 days following dosing in each intervention group. Screening for number of adverse events (AEs)and severe adverse events (SAEs) will done on all study visits. Adverse events screened for include: diarrhea, fever, vomiting, abdominal pain, itching, rash, nausea, weakness, cough, vertigo, and dryness of mouth. SAEs are those which are incapacitating, preventing normal activities, including death and hospitalization.	42 days

Collaborators and Investigators

• Sponsor: Sachin Desai
• Collaborators: Indian Council of Medical Research; National Institute of Cholera and Enteric Diseases, India
• Investigators: Principal Investigator: Suman Kanungo, MBBS, National Institute of Cholera and Enteric Diseases, India

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: April 11, 2012
• First Submitted That Met QC Criteria: April 16, 2012
• First Posted (Estimate): April 18, 2012

Study Record Updates

• Last Update Posted (Estimate): September 25, 2013
• Last Update Submitted That Met QC Criteria: September 24, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: safety and immunogenicity; killed oral cholera vaccine; boosting vaccine regimen
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vibrio Infections; Cholera; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CR-WC-11