Clinical trial NCT02145377: PXVX0200 (CVD103-HgR) vs Shanchol in Mali
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cholera
Keywords: Cholera
Vaccine
Mali
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Emergent BioSolutions
name: Shantha Biotechnics Limited
First posted: 2014-05-22
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: To elicit a significant rise in serum Inaba vibriocidal antibody after a single vaccination
timeFrame: 14 days
Secondary outcomes:
measure: To measure antibody response for a 10E8 dose and 10E9 dose of PXVX0200 oral vaccine
timeFrame: 14 days
measure: To plot the kinetics of the serum Inaba Vibriocidal antibody response
timeFrame: Baseline and post-vaccination time point.
measure: Assess fecal shedding of PXVX0200
timeFrame: Day 1-3, day 7 and day 14
measure: Compare rate of diarrhea
timeFrame: 7 days
Other outcomes:
measure: Plot seroconversion
timeFrame: Day 7, 14, 21, 28, 35 and 42
measure: Assess reactogenicity
timeFrame: For seven days after each dose of PXVX0200
Locations:
city: Bamako
country: Mali
facility: Centre pour le Développement des Vaccins, Mali (CVD-Mali)
Study officials:
affiliation: University of Maryland, College Park
name: Milagritos D Tapia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre pour le Developpement des Vaccins - Mali
name: Samba O Sow, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sow SO, Tapia MD, Chen WH, Haidara FC, Kotloff KL, Pasetti MF, Blackwelder WC, Traore A, Tamboura B, Doumbia M, Diallo F, Coulibaly F, Onwuchekwa U, Kodio M, Tennant SM, Reymann M, Lam DF, Gurwith M, Lock M, Yonker T, Smith J, Simon JK, Levine MM. Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial Comparing the Reactogenicity and Immunogenicity of a Single Standard Dose to Those of a High Dose of CVD 103-HgR Live Attenuated Oral Cholera Vaccine, with Shanchol Inactivated Oral Vaccine as an Open-Label Immunologic Comparator. Clin Vaccine Immunol. 2017 Dec 5;24(12):e00265-17. doi: 10.1128/CVI.00265-17. Print 2017 Dec.