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History of Changes for Study: NCT02823899
Safety and Immunogenicity of Locally Manufactured New (HL-OCV) Oral Cholera Vaccine
Latest version (submitted October 31, 2018) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 30, 2016 None (earliest Version on record)
2 January 7, 2017 Recruitment Status, Study Status and Contacts/Locations
3 August 23, 2017 Study Status
4 March 18, 2018 Recruitment Status, Study Status and Study Design
5 October 31, 2018 Sponsor/Collaborators and Study Status
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Study NCT02823899
Submitted Date:  June 30, 2016 (v1)
Open or close this module Study Identification
Unique Protocol ID: PR-16021
Brief Title: Safety and Immunogenicity of Locally Manufactured New (HL-OCV) Oral Cholera Vaccine
Official Title: A Phase I/II Dose-escalation Study to Evaluate Safety, Tolerability and Immunogenicity of '2-dose Primary Series' Single Strain (Hikojima Serotype) Inactivated Oral Cholera Vaccine Formulations (Two Formulations Based on Total O1 LPS Content), in Sequential Age Descending Population of Healthy Adults and Children
Secondary IDs:
Open or close this module Study Status
Record Verification: June 2016
Overall Status: Not yet recruiting
Study Start: July 2016
Primary Completion: November 2017 [Anticipated]
Study Completion: November 2017 [Anticipated]
First Submitted: June 22, 2016
First Submitted that
Met QC Criteria:		 June 30, 2016
First Posted: July 6, 2016 [Estimate]
Last Update Submitted that
Met QC Criteria:		 June 30, 2016
Last Update Posted: July 6, 2016 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
Responsible Party: Sponsor
Collaborators: Bill and Melinda Gates Foundation
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: Cholera, a rapidly dehydrating watery diarrheal disease transmitted through water or food contaminated with the bacterium, Vibrio cholerae, is a major cause of morbidity and mortality in low income countries like Bangladesh. In our country, Cholera disease burden consists of both cholera outbreaks and endemic cholera comprising at least 300,000 severe cases and 1.2 million infections each year. To combat this situation, Vaccination against cholera has been proved effective both in endemic and epidemic settings. But, the WHO recommended Dukoral and Prequalified Shanchol are quite expensive for our country perspective. Therefore, locally manufactured OCV can improve the cost effectiveness and make it affordable for all. The hypothesis of this proposal is that Locally produced orally administered whole cell inactivated HL-OCV test formulations A and B are safe and immunogenic in adults and children in Bangladesh as compared to ShancholTM. The results of the study will allow us to understand the safety and immunogenicity outcome of the HL-OCV compared to Shanchol vaccine. The total sample size will be 840 healthy participants. 840 healthy participants (360 adults, 240 Children and Adolescent and 240 young children) of 18-45 years, 5- less than 18 years and 1 year to less than 5 years will be enrolled in the study. Children whose parents/guardians give voluntary consent will be enrolled in the study. The investigators will provide 2 dose of vaccine for three groups in 14 days interval. Test formulations will be locally manufactured and the comparator group will get Shanchol. The Investigators propose to collect three blood samples (Day 0, 14 and 28).
Detailed Description:

Background : Cholera continues to be a major cause of morbidity and mortality in low income countries including Bangladesh. It is estimated that there are at least 300,000 severe cases and over 4,500 deaths in Bangladesh each year1. The overall morbidity for cholera remains high. A global stockpile of OCV has been created by WHO in 2013 for epidemic and outbreak settings30. However, the global demand for the vaccine far exceeds the present supply for both epidemic and also endemic settings3. It can be envisioned that local production of an affordable OCV for high risk population in endemic settings will improve the present scenario in Bangladesh and other countries.

Knowledge gap: The WHO recommends OCV for use in both endemic and epidemic cholera settings4. At present there are two vaccines that are WHO prequalified. These include Dukoral which is registered in Bangladesh and in over 50 countries. However, the disadvantage of use of Dukoral is that its current price is expensive for Bangladesh and other developing countries. In addition, the need for buffer to formulate the vaccine makes it less fieldable for mass vaccination programs.Another whole killed OCV, ShancholTM, which is WHO prequalified, is based on similar bacterial components as Dukoral and licensed in India but not in Bangladesh. Although this vaccine is relatively affordable it may not be sufficiently cost effective for the Government of Bangladesh to implement it in our poor endemic settings. At present, the vaccine is in short supply and will not be able to meet the global demands. In order to increase supply of OCV and make the vaccine more affordable, MSD Wellcome Trust Hilleman Labs. Pvt. Ltd in collaboration with Goteberg University, Sweden has engineered new oral cholera vaccine HL-OCV,consisting of formaldehyde-inactivated recombinant V.cholerae strain ,MS 1568 expressing both Ogawa and Inaba antigens. The vaccine formulation is quantified on total O1 lipopolysaccharide ,LPS content which is matched to that of ShancholTM ,not less than 600 mcg/ml LPS for O1; Formulation A and higher than Shanchol ,not less than 900 mcg/ml LPS for O1; Formulation B. The vaccine technology is transferred to local manufacturer ,INCEPTA in Bangladesh.

Relevance: The study of this locally manufactured new HL-OCV, among children and adults will be able to give us information regarding the safety and immunogenicity of two different formulations of vaccine, based on LPS content. The study will not only identify safe formulation among the two formulation A or B, but will also be able to show superiority of higher LPS formulation in most naive population in children who are 1-5 years of age. Results of the study will be able to identify and select most suitable formulation in Phase II study for licensure in Bangladesh. This study will further pave the way forward for field studies which could establish field efficacy of vaccine compared to existing vaccines in Bangladesh.

Hypothesis : Locally produced orally administered whole cell inactivated HL-OCV test formulations A and B are safe and immunogenic in adults and children in Bangladesh as compared to Shanchol TM.

Objectives: The objective of this study is to determine most safe and immunogenic formulation for new oral cholera vaccine HL-OCV, and comparing with licensed vaccine ShancholTM.
Open or close this module Conditions
Conditions: Cholera
Keywords: cholera vaccine
hikojima serotype
randomized trial
immunogenicity
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Prevention
Study Phase: Phase 1/Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 840 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: HL-OCV
Pharmaceutical company in Bangladesh is now producing HL-OCV, with technological support from MSD wellcome trust Hilleman pt. ltd, which meets international Good manufacturing practice( GMP) standards and WHO production guidelines.
 Biological: HL-OCV
Pharmaceutical company in Bangladesh is now producing HL-OCV, with technological support from MSD wellcome trust Hilleman pt. ltd, which meets international Good manufacturing practice( GMP) standards and WHO production guidelines.
Active Comparator: Shanchol
The vaccine is manufactured by Shantha Biotechnics in hyderabad, India and is prequalified by the WHO. Shanchol is available in a single dose. This vaccine is used as two dose regimen.
 Biological: Shanchol
The vaccine is manufactured by Shantha Biotechnics in hyderabad, India and is prequalified by the WHO. Shanchol is available in a single dose. This vaccine is used as two dose regimen.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Number of participants with vaccine related reactogenicity as assessed by study personnel.
[ Time Frame: Within 30 minutes after administration of vaccine ]

Number of participants having reactogenicity events will be compared between test group and comparator group
2. Number of participants with solicited adverse events as assessed by study personnel
[ Time Frame: Within 7 days after administration of vaccine ]

Number of participant having solicited adverse events observed after each dose of vaccination assessed by study personnel through home visit and will be compared between test group and comparator group.
3. Number of participants with unsolicited adverse event including serious adverse event as assessed by study personnel.
[ Time Frame: Within 14 days after administration of vaccine. ]
Secondary Outcome Measures:
1. Number of participant showing seroconversion of vibriocidal antibody against serogroup O1 Inaba
[ Time Frame: 14 days after administration of vaccine ]

Number of participants showing sero-conversion against V. cholerae O1 upon vaccination HL-OCV being tested in comparison with Shanchol TM .
2. Number of participant showing seroconversion of vibriocidal antibody against serogroup O1 Ogawa.
[ Time Frame: 14 days after administration of vaccine ]

Number of participants showing sero-conversion against V. cholerae O1 upon vaccination HL-OCV being tested in comparison with Shanchol TM .
Open or close this module Eligibility
Minimum Age: 1 Year
Maximum Age: 45 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: Yes
Criteria:

Inclusion Criteria:

  1. Age: 1years to less than 5 years for the younger children group; 5- less than18 years for older children and adolescent group and 18- 45 years (inclusive) for the adult group.
  2. Sex: Male, Female, Transgender.
  3. Consent: Informed consent from study participants and guardian in case of children along with assent in children 11-17 years (inclusive) of age.
  4. Apparently healthy.

Exclusion Criteria:

  1. Suffering from diarrhoea or abdominal pain or vomiting in the past 24 hours or diarrhoea lasting for more than 2 weeks in the past 6 months
  2. History of taking oral cholera vaccine.
  3. History of taking any other live or killed enteric vaccine in the last 8 weeks.
  4. History of anaphylaxis or serious vaccine reaction.
  5. Currently use of any immunosuppressive or immune-modifying drugs.
  6. Receipt of blood or blood products or parenteral immunoglobulin preparation in the past 3 months.
  7. Currently on antimicrobial therapy (taking antibiotics within 24 hours during screening and vaccination).
  8. Severe malnutrition defined as wt-for-ht z-score <-3.0 with or without oedema.
  9. For married females pregnancy or plans to become pregnant during the study period (as determined by verbal screening) will be excluded. In addition, pregnancy test will be done by pregnancy strip test before each day of vaccination (Day 0 and day 14) for married female.
  10. Culture positive V. cholerae, ETEC, Salmonella and Shigella in stool.
Open or close this module Contacts/Locations
Central Contact Person: Firdausi Qadri, Dr.
Telephone: 88-02-9827001-10 Ext. 2431
Email: fqadri@icddrb.org
Central Contact Backup: Fahima Chowdhury, Dr.
Telephone: 88-02-9827001-10 Ext. 3458
Email: fchowdhury@icddrb.org
Study Officials: Firdausi Qadri, Dr.
Study Director
International Centre for Diarrhoeal Disease Research, Bangladesh
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes
Data will be shared with MSD Wellcome Trust Hilleman Laboratories (P) Ltd.
Supporting Information:
Time Frame:
Access Criteria:
URL:
Open or close this module References
Citations: [Study Results] Ali M, Lopez AL, You YA, Kim YE, Sah B, Maskery B, Clemens J. The global burden of cholera. Bull World Health Organ. 2012 Mar 1;90(3):209-218A. doi: 10.2471/BLT.11.093427. Epub 2012 Jan 24. PubMed 22461716
[Study Results] Schwartz BS, Harris JB, Khan AI, Larocque RC, Sack DA, Malek MA, Faruque AS, Qadri F, Calderwood SB, Luby SP, Ryan ET. Diarrheal epidemics in Dhaka, Bangladesh, during three consecutive floods: 1988, 1998, and 2004. Am J Trop Med Hyg. 2006 Jun;74(6):1067-73. PubMed 16760521
[Study Results] Harris JB, LaRocque RC, Chowdhury F, Khan AI, Logvinenko T, Faruque AS, Ryan ET, Qadri F, Calderwood SB. Susceptibility to Vibrio cholerae infection in a cohort of household contacts of patients with cholera in Bangladesh. PLoS Negl Trop Dis. 2008 Apr 9;2(4):e221. doi: 10.1371/journal.pntd.0000221. PubMed 18398491
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