Effect of Extended Dose Intervals on the Immune Response to Oral Cholera Vaccine

NCT03373669 | Completed Phase 4

• 1 other identifier: IRB00008066
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Cholera is a life-threatening disease if prompt actions are not taken. The most recent estimates of the global burden of cholera estimate that there are more than 1.3 billion people at risk. Of which, 2.86 million (range: 1.3-4.0 million) will contract cholera and 95,000 (21,000-143,000) will die each year. A safe, effective, and affordable killed whole-cell oral cholera vaccine (OCV) is now being used widely to prevent cholera in areas at risk. This regimen demonstrated 65% efficacy retained for at least 3 years and even up to 5 years in an endemic setting. The primary aim of this project is to determine changes in the vibriocidal geometric mean titers (GMT) in subjects who receive the second dose of oral cholera vaccine (OCV) at different intervals: 2 weeks, or 6 months following the first dose of vaccine. Secondary aims include a) vibriocidal antibody response rates in subjects who receive OCV at 2 weeks or 6 months following the first dose of vaccine, b) age specific serum vibriocidal GMTs following the second dose among participants given the second dose of OCV at intervals of 2 weeks or 6 months following the first dose of vaccine, c) GMT and antibody response rates of Immunoglobulin A (IgA) and Immunoglobulin G (IgG) anti-lipopolysaccharide (anti-LPS) as measured by ELISA following the second dose among participants given the second dose of OCV at intervals of 2 weeks or 6 months following the first dose of vaccine. Our hypothesis is that the vibriocidal GMT following the second dose, when given after 6 months will not be inferior to the response when the second dose is given according to the standard interval of two weeks.

Conditions

Cholera; Vibrio Cholerae Infection

Keywords

oral cholera vaccine; OCV; dose interval

Outcome Measures

Primary Outcomes (1)

• Change in Vibriocidal GMT

  The primary aim of this project is to determine changes in the vibriocidal geometric mean titers (GMT) in subjects who receive the second dose of oral cholera vaccine (OCV) at different intervals: 2 weeks or 6 months following the first dose of vaccine.

  6 months

Secondary Outcomes (4)

• Vibriocidal Antibody Response Rates

  2 weeks and 6 months

• Age specific vibriocidal response

  2 weeks and 6 months

• IgG ELISA Antibody Response

  2 weeks and 6 months

• IgA ELISA Antibody Response

  2 weeks and 6 months

Study Arms (2)

Shanchol Dose-interval Group 1

ACTIVE COMPARATOR

Participants in Dose-Interval Group 1 (DIG-1) will receive the oral cholera vaccine, Shanchol, according to the manufacturer instructions: in 2 doses at Day 0 and two weeks later (Day 14).

Biological: Oral Cholera Vaccine

Shanchol Dose-Interval Group 2

EXPERIMENTAL

Participants in Dose-Interval Group 2 (DIG-2) will receive the Adjusted Dose oral cholera vaccine, Shanchol, with a delayed second dose. The vaccine will be given at Day 0 and six months later.

Biological: Adjusted Dose Oral Cholera Vaccine

Interventions

Oral Cholera Vaccine BIOLOGICAL

Shanchol is a bivalent (O1 and O139 serotypes) vaccine using a heat-killed classical Inaba strain and a formalin-killed classical Ogawa strain produced by Sanofi. Shanchol requires no oral buffer for administration, is approved for persons greater than 1 year of age, and requires 2 doses at two-week intervals. It became World Health Organization (WHO) prequalified in 2011.

Also known as: Shanchol

Shanchol Dose-interval Group 1

Adjusted Dose Oral Cholera Vaccine BIOLOGICAL

The Adjusted Dose Oral Cholera Vaccine is given in two doses, with the second dose given at six months, rather than the manufacturer described 2 week interval between first and second dose.

Also known as: Shanchol delayed dose

Shanchol Dose-Interval Group 2

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥1 year, stratified into different age groups
• Living in the Waya Clinic Catchment Area
• Good health condition, without clinically significant medical history (by participant or guardian, in case of minor)
• Not pregnant for female subjects.
• Available to participate for the study duration, including all planned follow-up visits for up to 9 months from screening.
• Signed informed consent

You may not qualify if:

• Presence of a significant medical or psychiatric condition (Examples include: Diagnosis and treatment of tuberculosis (TB) or HIV; renal insufficiency; hepatic disease; oral or parenteral medication known to affect the immune function, such as corticosteroids, other immunosuppressant drugs; or behavioural or memory issues)
• Ever having received oral cholera vaccine.
• Receipt of an investigational product (within 30 days before vaccination).
• History of diarrhoea in 7 days prior to first dose of vaccine (defined as ≥3 unformed loose stools in 24 hours).
• History of chronic diarrhea (lasting for more than 2 weeks in the past 6 months)
• Current use of laxatives, antacids, or other agents to lower stomach acidity?
• Planning to become pregnant in the next 2 years.

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead

Study Sites (1)

Center for Infectious Disease Research - Zambia

Lusaka, Zambia

Location

Related Publications (6)

• Ali M, Nelson AR, Lopez AL, Sack DA. Updated global burden of cholera in endemic countries. PLoS Negl Trop Dis. 2015 Jun 4;9(6):e0003832. doi: 10.1371/journal.pntd.0003832. eCollection 2015.

  PMID: 26043000 BACKGROUND

• Sridhar S. An affordable cholera vaccine: an important step forward. Lancet. 2009 Nov 14;374(9702):1658-60. doi: 10.1016/S0140-6736(09)61418-5. Epub 2009 Oct 8. No abstract available.

  PMID: 19819005 BACKGROUND

• Bi Q, Ferreras E, Pezzoli L, Legros D, Ivers LC, Date K, Qadri F, Digilio L, Sack DA, Ali M, Lessler J, Luquero FJ, Azman AS; Oral Cholera Vaccine Working Group of The Global Task Force on Cholera Control. Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2017 Oct;17(10):1080-1088. doi: 10.1016/S1473-3099(17)30359-6. Epub 2017 Jul 17.

  PMID: 28729167 BACKGROUND

• Bhattacharya SK, Sur D, Ali M, Kanungo S, You YA, Manna B, Sah B, Niyogi SK, Park JK, Sarkar B, Puri MK, Kim DR, Deen JL, Holmgren J, Carbis R, Dhingra MS, Donner A, Nair GB, Lopez AL, Wierzba TF, Clemens JD. 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2013 Dec;13(12):1050-6. doi: 10.1016/S1473-3099(13)70273-1. Epub 2013 Oct 18.

  PMID: 24140390 BACKGROUND

• Kanungo S, Desai SN, Nandy RK, Bhattacharya MK, Kim DR, Sinha A, Mahapatra T, Yang JS, Lopez AL, Manna B, Bannerjee B, Ali M, Dhingra MS, Chandra AM, Clemens JD, Sur D, Wierzba TF. Flexibility of oral cholera vaccine dosing-a randomized controlled trial measuring immune responses following alternative vaccination schedules in a cholera hyper-endemic zone. PLoS Negl Trop Dis. 2015 Mar 12;9(3):e0003574. doi: 10.1371/journal.pntd.0003574. eCollection 2015 Mar.

  PMID: 25764513 BACKGROUND

• Mwaba J, Chisenga CC, Xiao S, Ng'ombe H, Banda E, Shea P, Mabula-Bwalya C, Mwila-Kazimbaya K, Laban NM, Alabi P, Chirwa-Chobe M, Simuyandi M, Harris J, Iyer AS, Bosomprah S, Scalzo P, Murt KN, Ram M, Kwenda G, Ali M, Sack DA, Chilengi R, Debes AK. Serum vibriocidal responses when second doses of oral cholera vaccine are delayed 6 months in Zambia. Vaccine. 2021 Jul 22;39(32):4516-4523. doi: 10.1016/j.vaccine.2021.06.034. Epub 2021 Jul 1.

  PMID: 34217572 DERIVED

MeSH Terms

Conditions

Cholera

Interventions

Cholera Vaccines; shanchol

Condition Hierarchy (Ancestors)

Vibrio Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Amanda K Debes, PhD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open label, randomized, phase 2 clinical trial of the immunogenicity of OCV when the vaccine is administered to participants of three age cohorts (1-4 years, 5-14 years, and \>14 years) and in two dose interval groups (DIGs). The subjects in each age cohort will be randomized to a DIG of 2 weeks (DIG-1) or 6 months (DIG-2). A total of 120 subjects will be enrolled and these are equally divided between the different groups (20 per age/dose interval group).

Study Record Dates

• First Submitted: December 4, 2017
• First Posted: December 14, 2017
• Study Start: November 16, 2017
• Primary Completion: October 16, 2019
• Study Completion: December 1, 2020
• Last Updated: April 5, 2021

Record last verified: 2021-04

Locations

ZA (1)