PXVX0200 (CVD103-HgR) vs Shanchol in Mali

Cholera Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02145377
• Other study ID #: HP-00059690
• Status: Completed
• Phase: Phase 2
• Start date: July 2014
• Est. completion date: March 2015

Study information

• Verified date: September 2019
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholera

Intervention

Biological:
• PXVX0200 10E8
Oral dose of PXVX0200 10E8
• PXVX0200 10E9
Oral dose of PXVX0200 10E9
• Placebo
Oral dose of sodium bicarbonate buffer
• Shanchol
Licensed comparator

Locations

Country	Name	City	State
Mali	Centre pour le Développement des Vaccins, Mali (CVD-Mali)	Bamako

Sponsors (3)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	PaxVax, Inc., Shantha Biotechnics Limited

Country where clinical trial is conducted

Mali, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plot seroconversion	To plot the seroconversion (= 4-fold increase over baseline), mean fold rise (comparing baseline titer with post-vaccination titer), and kinetics of serum IgG cholera antitoxin antibody following the ingestion of a single oral dose of PXVX0200 (CVD 103-HgR) containing =2 x10E8 cfu or =2 x10E9 cfu versus Shanchol™.	Day 7, 14, 21, 28, 35 and 42
Other	Assess reactogenicity	Assess tiredness, vomiting, loss of appetite, abdominal pain and headache	For seven days after each dose of PXVX0200
Primary	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	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
Secondary	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.
Secondary	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
Secondary	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