Bridging Study for Killed Oral Cholera Vaccine in Ethiopia

This study has been completed.
Sponsor:
Collaborators:
Armauer Hansen Research Institute, Ethiopia
Federal Ministry of Health, Ethiopia
Shantha Biotechnics Limited, India
Information provided by (Responsible Party):
International Vaccine Institute
ClinicalTrials.gov Identifier:
NCT01524640
First received: January 31, 2012
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

This is a randomized, double blind, placebo controlled trial to confirm the safety and determine the immune response of the killed oral cholera vaccine in healthy adults and children in Ethiopia.


Condition Intervention Phase
Vibrio Cholerae
Cholera
Biological: Killed Bivalent (O1 and O139) whole cell oral cholera vaccine
Biological: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Double-blind, Controlled Trial to Evaluate the Safety and Immunogenicity of Killed Bivalent (o1 and o139) Whole-cell Based Oral Cholera Vaccine (Shanchol®) in Healthy Individuals in Ethiopia

Resource links provided by NLM:


Further study details as provided by International Vaccine Institute:

Primary Outcome Measures:
  • Proportion of subjects given investigational product with adverse events. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    1. Immediate reactions within 30 minutes after each dose
    2. Serious Adverse Events occurring 14 days following each dose
    3. Reactogenicity: Headache, vomiting, nausea, abdominal pain/cramps, diarrhea, fever, loss of appetite within three days

    i. Diarrhea is defined as having 3 or more loose/watery stools within a 24 hour period.

    ii. Fever is defined as having an oral or axillary temperature of ≥ 38oC


  • Proportion of subjects exhibiting 4-fold or greater rises in titers of serum vibriocidal antibodies, relative to baseline, 14 days after second dose. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects exhibiting 4-fold or greater rises in titers of serum vibriocidal antibodies, relative to baseline, 14 days after the first dose. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Geometric mean serum vibriocidal titers at baseline, 14 days after each dose of the investigational product. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Severe adverse event within 28 days following each dose of investigational product. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 216
Study Start Date: December 2012
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Killed oral cholera vaccine

Killed Bivalent (O1 and O139) Whole cell oral cholera vaccine (Shanchol TM) Vaccine strain Reformulated version

V. cholerae O1 Inaba El Tor strain Phil 6973 formalin killed 600 Elisa units (EU) of lipopolysaccharide (LPS) V. cholerae O1 Ogawa classical strain Cairo 50 heat killed 300 EU LPS V. cholerae O1 Ogawa classical strain Cairo 50 formalin killed 300 EU LPS V. cholerae O1 Inaba classical strain Cairo 48 heat killed 300 EU LPS V. cholerae O139 strain 4260B formalin killed 600 EU LPS

Biological: Killed Bivalent (O1 and O139) whole cell oral cholera vaccine
1.5 ml single dose oral administration on day 0 and day 14
Other Name: Shanchol TM
Placebo Comparator: Placebo

Non biologic placebo

Ingredients Per 1.5 ml dose

  1. Starch 60mg
  2. Red color[1mg/ml] 10 µl
  3. Yellow color [1mg/ml] 5 µl
  4. Xanthum Gum (1% solution) 300 µl
  5. Water for Injection Upto 1.5 ml

All the above ingredients are of pharmaceutical grade.

Non-biological placebo of above composition has been used in 2010 for "Randomized, double-blind, placebo controlled trial to evaluate the safety and immunogenicity of orally administered, killed, bivalent whole-cell , cholera vaccine, Shanchol in Bangladeshi Adults and Children". This study involving 330 subjects was carried out at International Center for Diarrheal Disease Research Bangladesh (ICDDR,B) located in Dhaka, Bangladesh with Dr. Firdausi Qadri as Principal Investigator (NCT01042951). There were no safety concerns associated with this placebo in this study and the report of this study has been submitted to the National Regulators in Bangladesh and the World Health Organization.

Biological: Placebo
1.5 ml oral administration on day 0 and day 14
Other Name: Non biologic placebo

Detailed Description:

This study serves as a bridging trial to evaluate the safety and immunogenicity of a two dose regimen of the WC-OCV (Shanchol®) in Ethiopian population. In order to assess whether the bivalent killed oral cholera vaccine may be used safely among those who are most at risk for cholera, we need to determine the safety and immunogenicity of the killed oral cholera vaccine. The vaccine was evaluated in a large number of human subjects in India Vietnam, and Bangladesh, in which it has demonstrated safety, immunogenicity, and clinical protective efficacy. Though we do not expect the vaccine to act differently in the Ethiopian population, we aim to confirm our presumptive understanding that two doses of WC-OCV is safe and immunogenic in healthy volunteers at one year and above (exclusive of pregnant women). Findings from this study can pave the way for the possible use of the killed whole cell oral cholera vaccine in both endemic and outbreak settings at a larger scale.

  Eligibility

Ages Eligible for Study:   1 Year and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or female adults aged 18 years and above; and children aged 1 -17 years who is available for follow-up visits and specimen collection.

    • The subject should be able to continue in the study for the next 4 weeks
    • The subject (or parent/guardian) should be willing to provide 3 blood samples
  2. For females of reproductive age, non-pregnant (as determined by urine pregnancy test).
  3. Written informed consent obtained from the subjects or their parents/guardians, and written assent obtained from children aged 12 - 17 years.
  4. Healthy subjects as determined by:

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

Exclusion Criteria:

  1. Ongoing chronic recurring illness which may cause systemic symptoms as judged by the investigating physician.
  2. Ongoing acute illness.
  3. For females of reproductive age: Pregnancy (or females planning to become pregnant during the study period; as determined by verbal screening)
  4. Immunocompromising condition or on chronic systemic steroid therapy
  5. Diarrhea (3 or more loose/more watery stools within a 24-hour period) within 6 weeks prior to enrollment
  6. Intake of any anti-diarrhea medicine in the past week
  7. Abdominal pain or cramps, loss of appetite, nausea, or vomiting in the past 24 hours
  8. Temperature ≥38ºC (oral or axillary) warrants deferral of the vaccination pending recovery of the subject
  9. Previous hypersensitivity to formaldehyde.
  10. Receipt of immunoglobulin or any blood product during the past 3 months
  11. Receipt of oral cholera vaccine in the past three years
  12. Any potential subject currently participating or who will participate within the next six months in another clinical trial
  13. Positive screening urine pregnancy test for females greater than 12 years of age
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01524640

Locations
Ethiopia
Armauer Hansen Research Institute
Addis Ababa, Oromia, Ethiopia
Sponsors and Collaborators
International Vaccine Institute
Armauer Hansen Research Institute, Ethiopia
Federal Ministry of Health, Ethiopia
Shantha Biotechnics Limited, India
  More Information

No publications provided

Responsible Party: International Vaccine Institute
ClinicalTrials.gov Identifier: NCT01524640     History of Changes
Other Study ID Numbers: CR-WC-09
Study First Received: January 31, 2012
Last Updated: September 24, 2013
Health Authority: South Korea: International Vaccine Institute
Ethiopia: National Regulatory Agency
Ethiopia: Food Medicine and Administration and Control Authority
Ethiopia: Armauer Hansen Research Institute

Keywords provided by International Vaccine Institute:
oral cholera vaccine
safety and immunogenicity
bridging study
ethiopia

Additional relevant MeSH terms:
Cholera
Vibrio Infections
Gram-Negative Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on September 14, 2014