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PXVX0200 (CVD103-HgR) vs Shanchol in Mali

Primary Purpose

Cholera

Status

Completed

Phase

Phase 2

Locations

Mali

Study Type

Interventional

Intervention

PXVX0200 10E8

PXVX0200 10E9

Placebo

Shanchol

About this trial

This is an interventional prevention trial for Cholera focused on measuring Cholera, Vaccine, Mali

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Arm Label

PXVX0200 10E8 then placebo

Placebo, then PXVX0200 10E8

PXVX0200 10E9 then Placebo

Placebo then PXVX0200 10E9

Shanchol

Arm Description

PXVX0200 10E8 on day 0; Placebo on day 14

Placebo on day 0; PXVX0200 10E8 on day 14

PXVX0200 10E9 on day 0; Placebo on day 14

Placebo on day 0; PXVX0200 10E9 on day 14

Two doses of Shanchol, on day 0 and day 14

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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).

Assess fecal shedding of PXVX0200

Shedding of CVD 103-HgR in stool as determined by stool culture (whole specimen or rectal swab)

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

Full Information

NCT ID

NCT02145377

First Posted

May 20, 2014

Last Updated

September 24, 2019

Sponsor

University of Maryland, Baltimore

Collaborators

Emergent BioSolutions, Shantha Biotechnics Limited

1. Study Identification

Unique Protocol Identification Number

NCT02145377

Brief Title

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

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

July 2014 (undefined)

Primary Completion Date

March 2015 (Actual)

Study Completion Date

March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Maryland, Baltimore

Collaborators

Emergent BioSolutions, Shantha Biotechnics Limited

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cholera

Keywords

Cholera, Vaccine, Mali

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

150 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PXVX0200 10E8 then placebo

Arm Type

Experimental

Arm Description

PXVX0200 10E8 on day 0; Placebo on day 14

Arm Title

Placebo, then PXVX0200 10E8

Arm Type

Experimental

Arm Description

Placebo on day 0; PXVX0200 10E8 on day 14

Arm Title

PXVX0200 10E9 then Placebo

Arm Type

Experimental

Arm Description

PXVX0200 10E9 on day 0; Placebo on day 14

Arm Title

Placebo then PXVX0200 10E9

Arm Type

Experimental

Arm Description

Placebo on day 0; PXVX0200 10E9 on day 14

Arm Title

Shanchol

Arm Type

Active Comparator

Arm Description

Two doses of Shanchol, on day 0 and day 14

Intervention Type

Biological

Intervention Name(s)

PXVX0200 10E8

Intervention Description

Oral dose of PXVX0200 10E8

Intervention Type

Biological

Intervention Name(s)

PXVX0200 10E9

Intervention Description

Oral dose of PXVX0200 10E9

Intervention Type

Biological

Intervention Name(s)

Placebo

Intervention Description

Oral dose of sodium bicarbonate buffer

Intervention Type

Biological

Intervention Name(s)

Shanchol

Intervention Description

Licensed comparator

Primary Outcome Measure Information:

Title

To elicit a significant rise in serum Inaba vibriocidal antibody after a single vaccination

Description

Time Frame

14 days

Secondary Outcome Measure Information:

Title

To measure antibody response for a 10E8 dose and 10E9 dose of PXVX0200 oral vaccine

Description

Time Frame

14 days

Title

To plot the kinetics of the serum Inaba Vibriocidal antibody response

Description

Time Frame

Baseline and post-vaccination time point.

Title

Assess fecal shedding of PXVX0200

Description

Shedding of CVD 103-HgR in stool as determined by stool culture (whole specimen or rectal swab)

Time Frame

Day 1-3, day 7 and day 14

Title

Compare rate of diarrhea

Description

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

Time Frame

7 days

Other Pre-specified Outcome Measures:

Title

Plot seroconversion

Description

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™.

Time Frame

Day 7, 14, 21, 28, 35 and 42

Title

Assess reactogenicity

Description

Assess tiredness, vomiting, loss of appetite, abdominal pain and headache

Time Frame

For seven days after each dose of PXVX0200

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Milagritos D Tapia, MD

Organizational Affiliation

University of Maryland, College Park

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Samba O Sow, MD, MS

Organizational Affiliation

Centre pour le Developpement des Vaccins - Mali

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Bamako

Country

Mali

12. IPD Sharing Statement

Citations:

PubMed Identifier

29021299

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.

Results Reference

derived

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PXVX0200 (CVD103-HgR) vs Shanchol in Mali

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