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.

Study Overview

• Status: Completed
• Conditions: Cholera
• Intervention / Treatment: Biological: PXVX0200 10E8; Biological: Placebo; Biological: PXVX0200 10E9; Biological: Shanchol

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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mali
  • Bamako, Mali
    • Centre pour le Développement des Vaccins, Mali (CVD-Mali)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Assess reactogenicity	Assess tiredness, vomiting, loss of appetite, abdominal pain and headache	For seven days after each dose of PXVX0200

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Emergent BioSolutions; Shantha Biotechnics Limited
• Investigators: Principal Investigator: Samba O Sow, MD, MS, Centre pour le Developpement des Vaccins - Mali

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: May 20, 2014
• First Submitted That Met QC Criteria: May 21, 2014
• First Posted (Estimate): May 22, 2014

Study Record Updates

• Last Update Posted (Actual): September 26, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Vaccine; Cholera; Mali
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vibrio Infections; Cholera
• Other Study ID Numbers: HP-00059690