PXVX0200 (CVD103-HgR) vs Shanchol in Mali

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Cholera

Intervention / Treatment
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* Biological: PXVX0200 10E8
* Biological: PXVX0200 10E9
* Biological: Placebo
* Biological: Shanchol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PXVX0200 10E8 then placebo<br>PXVX0200 10E8 on day 0; Placebo on day 14 | Biological: PXVX0200 10E8<br>* Oral dose of PXVX0200 10E8<br>Biological: Placebo<br>* Oral dose of sodium bicarbonate buffer<br>|
| Experimental: Placebo, then PXVX0200 10E8<br>Placebo on day 0; PXVX0200 10E8 on day 14 | Biological: PXVX0200 10E8<br>* Oral dose of PXVX0200 10E8<br>Biological: Placebo<br>* Oral dose of sodium bicarbonate buffer<br>|
| Experimental: PXVX0200 10E9 then Placebo<br>PXVX0200 10E9 on day 0; Placebo on day 14 | Biological: PXVX0200 10E9<br>* Oral dose of PXVX0200 10E9<br>Biological: Placebo<br>* Oral dose of sodium bicarbonate buffer<br>|
| Experimental: Placebo then PXVX0200 10E9<br>Placebo on day 0; PXVX0200 10E9 on day 14 | Biological: PXVX0200 10E9<br>* Oral dose of PXVX0200 10E9<br>Biological: Placebo<br>* Oral dose of sodium bicarbonate buffer<br>|
| Active Comparator: Shanchol<br>Two doses of Shanchol, on day 0 and day 14 | Biological: Shanchol<br>* Licensed comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To elicit a significant rise in serum Inaba vibriocidal antibody after a single vaccination | A comparison of the ability of a single ≥2 x10E9 cfu oral dose versus a single ≥2 x10E8 cfu oral dose of PXVX0200 (CVD 103-HgR) versus placebo to elicit a significant (> 4-fold) rise in serum Inaba vibriocidal antibody 14 days after vaccination, compared to baseline | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure antibody response for a 10E8 dose and 10E9 dose of PXVX0200 oral vaccine | To compare the ability of a single ≥2 x108 cfu dose of PXVX0200 (CVD 103-HgR) or ≥2 x109 oral dose of PXVX0200 (CVD 103-HgR) versus Shanchol™ to elicit serum Inaba vibriocidal antibody mean fold rise (compared to baseline titer) and GMT | 14 days | 
| To plot the kinetics of the serum Inaba Vibriocidal antibody response | To plot the kinetics of the serum Inaba vibriocidal antibody response after ingestion of a single oral dose of PXVX0200 (CVD 103-HgR) containing ≥2 x10E8 cfu or ≥2 x10E9 cfu versus Shanchol™. (With GMT on the Y axis and time points on the X axis, the GMTs at baseline and at each post-vaccination time point will be connected as a line graph). | Baseline and post-vaccination time point. | 
| Assess fecal shedding of PXVX0200 | Shedding of CVD 103-HgR in stool as determined by stool culture (whole specimen or rectal swab) | Day 1-3, day 7 and day 14 | 
| Compare rate of diarrhea | To compare the rate of diarrhea (≥ 4 loose stools within 24 hours) following administration of each vaccine regimen versus placebo over 7 days of follow-up | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholera, Vaccine, Mali