PXVX0200 (CVD103-HgR) vs Shanchol in Mali

A Phase 2 Randomized, Double-Blinded Study to Compare in Malian Adults the Immunogenicity, Clinical Acceptability and Excretion Pattern Following the Ingestion of a Single Dose of PXVX0200 (CVD 103-HgR) Live Oral Cholera Vaccine Containing Either 108 Colony Forming Units [Cfu] or 109 Cfu Using Shanchol™ Killed Whole Cell Oral Cholera Vaccine as an Immunological Comparator

To compare the ability of a single dose of PXVX0200 at two different dose levels, to placebo to elicit a significant antibody response 14 days after vaccination, compared to baseline.

To compare the ability of a single dose of PXVX0200 to a comparator vaccine Shanchol, a two dose administration, to elicit antibody response by 14 days after vaccination.

Currently there are two licensed inactivated vibrio oral vaccines (Dukoral® [Crucell; Leiden, The Netherlands] and Shanchol™ [Shantha Biotechnics; Hyderabad, India]) that are pre-qualified by the World Health Organization (WHO) for procurement by United Nations (UN) agencies. Each of these vaccines requires a two-dose regimen which is difficult to implement in the face of explosive outbreaks of cholera in unsettled situations in developing countries. For this reason there is great interest in identifying a cholera vaccine that can provide rapid onset of protection following the ingestion of just a single oral dose.

This Phase 2 randomized, observer-blinded and subject-blinded clinical trial to be conducted in Bamako, Mali will assess the immunogenicity of the 10^8 cfu versus the 10^9 cfu formulation of PaxVax-manufactured CVD 103-HgR.

Inclusion Criteria:

• Able to understand the study and give consent (either written or through a process that involves audio tapes explaining all aspects of the study and the consent form in local languages [Bambara and French] followed by making a mark and signature by a literate witness)
• Healthy men or women, age 18 to 45 years (inclusive) without significant medical history
• Women of child-bearing potential must have negative urine pregnancy test at baseline, prior to vaccination. They must also be willing to use adequate birth control for the duration of the 28-day study and have additional pregnancy tests if indicated. Effective methods of birth control for this study include abstinence, intrauterine device (IUD), oral or depot contraceptive, or barrier plus spermicide
• Willingness to remain in the study area until at least 42 days after receipt of the first vaccine dose

Exclusion Criteria:

• Health care workers who have direct contact with patients who are immune deficient, HIV-positive, or have an unstable medical condition
• Clinically significant history of immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurologic illness, psychiatric disorder requiring hospitalization, current drug or alcohol abuse
• History of an abnormal stool pattern or regular use of laxatives
• Previously received a licensed or investigational cholera vaccine
• History of cholera illness