CholeraPhase 3NCT01895855

Safety and Efficacy Challenge Study of Live Oral Cholera Vaccine Candidate,PXVX0200, to Prevent Cholera

A Phase 3 study testing PXVX0200 in people with Cholera, run by Bavarian Nordic at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of the study is to determine if PXVX0200 is safe and effective in preventing cholera infection Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Cholera
What is being tested?: PXVX0200
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 197 participants
Where: 3 sitesUnited States
Study dates: Sep 2013to Nov 2014
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

healthy men or women,
age 18 to 45 years inclusive;
normal medical history and physical examination; and
no clinically significant abnormalities from:
urine dipstick for glucose, protein, and blood
complete blood count,

Show all 13Show fewer

serum hepatic transaminases,
total bilirubin (direct if abnormal),
creatinine,
electrolytes,
albumin, or
electrocardiogram.
Women must have a negative pregnancy test.

Who cannot join

travel to a cholera endemic area in the previous 5 years;
abnormal stool pattern or regular use of laxatives;
history of eating disorders (such as bulimia), anal or rectal disorders, allergy to tetracycline and/or ciprofloxacin;
history of cholera or enterotoxigenic E. coli challenge or infection;
current or recent antibiotic use;
pregnancy or nursing;

Show all 9Show fewer

positive serology for HIV, hepatitis B antigen, or hepatitis C;
any immunosuppressive medical condition;
history of hospitalization for psychiatric illness or use of specific psychiatric drugs.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

University of Maryland Baltimore
Baltimore, Maryland, 21201
University of Vermont
Burlington, Vermont, 05405
Cincinnati Children'S Hospital Medical Center
Cincinnati, Ohio, 45229

Other trials in United States

About this study

Official title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Efficacy Trial of a Single Dose Live Oral Cholera Vaccine, PXVX0200 CVD 103-HgR, in Preventing Cholera Following Challenge With Vibrio Cholerae 10 Days or 3 Months After Vaccination

The purpose of the study is to determine if PXVX0200 is safe and effective in preventing cholera infection

Read the detailed description

A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Efficacy Trial of a Single Dose of Live Oral Cholera Vaccine Candidate, PXVX0200 CVD 103-HgR Strain, in Preventing Cholera following Challenge with Vibrio cholerae O1 El Tor Inaba 10 Days or 3 Months after Vaccination in volunteers aged 18-45 years

Conditions: Cholera
Being tested: PXVX0200, placebo
Medical subject headings: Cholera

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PXVX0200Biological
Single dose; liquid suspension after reconstitution with buffer; 5x10^8
placeboBiological

Study groups in NCT01895855
Study group	Role	What they receive
PXVX0200	Experimental	Biological: PXVX0200 Single dose; liquid suspension after reconstitution with buffer; 5x10^8 CFU Receives: Biological: PXVX0200
Placebo	Placebo comparator	Biological: Placebo physiological saline Receives: Biological: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

% of Participants With Moderate to Severe Diarrhea
Determine whether a single dose of PXVX0200 provides significantly greater protection than placebo against a challenge with virulent V. cholerae O1 El Tor Inaba at 10 days after vaccination. The primary endpoint was the occurrence of moderate or severe (>/= 3 liters) diarrhea.
Measured: Ten days after vaccination
% of Participants With Moderate to Severe Diarrhea
Determine whether a single dose of PXVX0200 provides significant greater protection than placebo against a challenge with virulent V. cholerae O1 El Tor Inaba at 3 months after vaccination. The primary endpoint was the occurrence of moderate or severe (>/= 3 liters) of diarrhea.
Measured: Ninety days after vaccination

Secondary outcomes (11)

Total Weight of Diarrheal Stools Following the 10 Day Cholera Challenge
Total weight (converted to volume) per subject of diarrheal stools measured from subjects with diarrhea following the 10 day cholera challenge.
Measured: Through 10 Days following challenge
Total Weight of Diarrheal Stools Following the 90 Day Cholera Challenge
Total weight (converted to volume) per subject of diarrheal stools measured from subjects with diarrhea following the 90 day cholera challenge.
Measured: Through 10 Days following challenge
% of Participants With Diarrhea of Any Severity Following a 10 Day Cholera Challenge
Incidence of mild or worse (any severity) diarrhea following the 10 day cholera challenge.
Measured: Through 10 Days following challenge
% of Participants With Diarrhea of Any Severity Following a 90 Day Challenge
Incidence of mild or worse (any severity) diarrhea following the 90 day cholera challenge.
Measured: Through 10 Days following challenge
% of Participants With Fever Following the 10 Day Cholera Challenge
Incidence of mild or worse fever following the 10 day cholera challenge.
Measured: Through 10 Days following challenge
% of Participants With Fever Following the 90 Day Cholera Challenge
Incidence of mild or worse fever following the 90 day cholera challenge.
Measured: Through 10 Days following challenge
Number of Days With Fecal Shedding Following 10 Day Challenge
Number of days of fecal shedding of wild type V. cholerae following 10 Day Challenge.
Measured: Through 10 Days post challenge
Number of Days With Fecal Shedding Following 90 Day Challenge
Number of days of fecal shedding of wild type V. cholerae following 90 Day Challenge
Measured: Through 10 days following challenge
# of Days With Positive Stool Culture Following 10 Day Cholera Challenge
Total number of days with a positive stool culture following the 10 Day Cholera challenge.
Measured: Through 10 Days following challenge
# of Days With Positive Stool Culture Following 90 Day Cholera Challenge
Total number of days with a positive stool culture following 90 Day Cholera Challenge
Measured: Through 10 Days following challenge
% of Participants With Reactogenicity, Diarrhea, Fever or Unsolicited Adverse Events Following Vaccination
Incidence and severity of signs and symptoms of reactogenicity such as diarrhea, and fever following vaccination (through Day 8).
Incidence and severity of unsolicited adverse events following vaccination (through Day 29).
Measured: Following vaccination (Days 1 - 8) and to Day 29

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2013Nov 2014

First posted11 Jul 2013 (estimated)
Study startSep 2013
Primary completionNov 2014
Study completionNov 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for CholeraStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 197 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01895855
Sponsor's protocol ID: PXVX-VC-200-003
Status last verified: Jun 2023
First submitted: 5 Jul 2013
Last updated: 28 Jun 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Chen WH, Cohen MB, Kirkpatrick BD, Brady RC, Galloway D, Gurwith M, Hall RH, Kessler RA, Lock M, Haney D, Lyon CE, Pasetti MF, Simon JK, Szabo F, Tennant S, Levine MM. Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor. Clin Infect Dis. 2016 Jun 1;62(11):1329-1335. doi: 10.1093/cid/ciw145. Epub 2016 Mar 21.
PubMed 27001804
Haney DJ, Lock MD, Gurwith M, Simon JK, Ishioka G, Cohen MB, Kirkpatrick BD, Lyon CE, Chen WH, Sztein MB, Levine MM, Harris JB. Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera vaccine are associated with protection against Vibrio cholerae infection. Vaccine. 2018 May 11;36(20):2768-2773. doi: 10.1016/j.vaccine.2018.04.011. Epub 2018 Apr 11.
PubMed 29655627
Haney DJ, Lock MD, Simon JK, Harris J, Gurwith M. Antibody-Based Correlates of Protection Against Cholera Analysis of a Challenge Study in a Cholera-Naive Population. Clin Vaccine Immunol. 2017 May 31;24(8):e00098-17. doi: 10.1128/CVI.00098-17. Online ahead of print.
PubMed 28566334
Hossain M, Islam K, Kelly M, Mayo Smith LM, Charles RC, Weil AA, Bhuiyan TR, Kovac P, Xu P, Calderwood SB, Simon JK, Chen WH, Lock M, Lyon CE, Kirkpatrick BD, Cohen M, Levine MM, Gurwith M, Leung DT, Azman AS, Harris JB, Qadri F, Ryan ET. Immune responses to O-specific polysaccharide (OSP) in North American adults infected with Vibrio cholerae O1 Inaba. PLoS Negl Trop Dis. 2019 Nov 19;13(11):e0007874. doi: 10.1371/journal.pntd.0007874. eCollection 2019 Nov.
PubMed 31743334
Islam K, Hossain M, Kelly M, Mayo Smith LM, Charles RC, Bhuiyan TR, Kovac P, Xu P, LaRocque RC, Calderwood SB, Simon JK, Chen WH, Haney D, Lock M, Lyon CE, Kirkpatrick BD, Cohen M, Levine MM, Gurwith M, Harris JB, Qadri F, Ryan ET. Anti-O-specific polysaccharide (OSP) immune responses following vaccination with oral cholera vaccine CVD 103-HgR correlate with protection against cholera after infection with wild-type Vibrio cholerae O1 El Tor Inaba in North American volunteers. PLoS Negl Trop Dis. 2018 Apr 6;12(4):e0006376. doi: 10.1371/journal.pntd.0006376. eCollection 2018 Apr.
PubMed 29624592

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Cholera trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Efficacy Trial of a Single Dose Live Oral Cholera Vaccine, PXVX0200 CVD 103-HgR, in Preventing Cholera Following Challenge With Vibrio Cholerae 10 Days or 3 Months After Vaccination
ClinicalTrials.gov ID: NCT01895855
Acronym / sponsor ID: PXVX-VC-200-003
Conditions: Cholera
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 197 participants (actual)
Lead sponsor: Bavarian NordicIndustry (pharma, biotech, devices)
Collaborators: Emergent BioSolutions
Study start: Sep 2013
Primary completion: Nov 2014 (actual)
Study completion: Nov 2014 (actual)
First posted: 11 Jul 2013 (estimated)
Results: Posted 1 Apr 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of the study is to determine if PXVX0200 is safe and effective in preventing cholera infection

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
PXVX0200	Experimental	Biological: PXVX0200Biological: PXVX0200 Single dose; liquid suspension after reconstitution with buffer; 5x10^8 CFU
Placebo	Placebo comparator	Biological: placeboBiological: Placebo physiological saline

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (13 listed)

healthy men or women,
age 18 to 45 years inclusive;
normal medical history and physical examination; and
no clinically significant abnormalities from:
urine dipstick for glucose, protein, and blood

Key exclusion criteria (9 listed)

travel to a cholera endemic area in the previous 5 years;
abnormal stool pattern or regular use of laxatives;
history of eating disorders (such as bulimia), anal or rectal disorders, allergy to tetracycline and/or ciprofloxacin;
history of cholera or enterotoxigenic E. coli challenge or infection;
current or recent antibiotic use;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PXVX0200Single dose; liquid suspension after reconstitution with buffer; 5x10^8	Biological	PXVX0200
placebo	Biological	Placebo

Primary outcome

% of Participants With Moderate to Severe Diarrhea
Time frame: Ten days after vaccination
Determine whether a single dose of PXVX0200 provides significantly greater protection than placebo against a challenge with virulent V. cholerae O1 El Tor Inaba at 10 days after vaccination. The primary endpoint was the occurrence of moderate or severe (>/= 3 liters) diarrhea.
% of Participants With Moderate to Severe Diarrhea
Time frame: Ninety days after vaccination
Determine whether a single dose of PXVX0200 provides significant greater protection than placebo against a challenge with virulent V. cholerae O1 El Tor Inaba at 3 months after vaccination. The primary endpoint was the occurrence of moderate or severe (>/= 3 liters) of diarrhea.

11 secondary outcomes

Total Weight of Diarrheal Stools Following the 10 Day Cholera Challenge
Time frame: Through 10 Days following challenge
Total Weight of Diarrheal Stools Following the 90 Day Cholera Challenge
Time frame: Through 10 Days following challenge
% of Participants With Diarrhea of Any Severity Following a 10 Day Cholera Challenge
Time frame: Through 10 Days following challenge
% of Participants With Diarrhea of Any Severity Following a 90 Day Challenge
Time frame: Through 10 Days following challenge
% of Participants With Fever Following the 10 Day Cholera Challenge
Time frame: Through 10 Days following challenge
% of Participants With Fever Following the 90 Day Cholera Challenge
Time frame: Through 10 Days following challenge
Number of Days With Fecal Shedding Following 10 Day Challenge
Time frame: Through 10 Days post challenge
Number of Days With Fecal Shedding Following 90 Day Challenge
Time frame: Through 10 days following challenge
# of Days With Positive Stool Culture Following 10 Day Cholera Challenge
Time frame: Through 10 Days following challenge
# of Days With Positive Stool Culture Following 90 Day Cholera Challenge
Time frame: Through 10 Days following challenge
% of Participants With Reactogenicity, Diarrhea, Fever or Unsolicited Adverse Events Following Vaccination
Time frame: Following vaccination (Days 1 - 8) and to Day 29

Results and safety

Results posted to the registry on 1 Apr 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PXVX0200	95	95
Placebo	102	102

Primary outcome: % of Participants With Moderate to Severe Diarrhea

Time frame: Ten days after vaccination. Number. Unit: percentage of participants

Measure	PXVX0200 n = 35	Placebo n = 66
Value	5.7	59.1

PXVX0200 vs Placebo: Vaccine Efficacy: 90.3

Primary outcome: % of Participants With Moderate to Severe Diarrhea

Time frame: Ninety days after vaccination. Number. Unit: percentage of participants

Measure	PXVX0200 n = 33	Placebo n = 66
Value	12.1	59.1

PXVX0200 vs Placebo: Vaccine Efficacy: 79.5

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: Unsolicited adverse events were recorded for each vaccine or placebo recipient from the day of vaccination through 28 days after vaccination or 28 days after challenge, whichever was later. SAEs and medically attended AEs were recorded through the end of the follow-up period (Day 181).. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PVXV0200	0 of 95 (0%)	17 of 95 (17.9%)	0 of 95
Placebo	2 of 102 (2%)	17 of 102 (16.7%)	0 of 102

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27001804Chen WH, Cohen MB, Kirkpatrick BD, Brady RC, Galloway D, Gurwith M, Hall RH, Kessler RA, Lock M, Haney D, Lyon CE, Pasetti MF, Simon JK, Szabo F, Tennant S, Levine MM. Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor. Clin Infect Dis. 2016 Jun 1;62(11):1329-1335. doi: 10.1093/cid/ciw145. Epub 2016 Mar 21.
Results publication: PubMed 29655627Haney DJ, Lock MD, Gurwith M, Simon JK, Ishioka G, Cohen MB, Kirkpatrick BD, Lyon CE, Chen WH, Sztein MB, Levine MM, Harris JB. Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera vaccine are associated with protection against Vibrio cholerae infection. Vaccine. 2018 May 11;36(20):2768-2773. doi: 10.1016/j.vaccine.2018.04.011. Epub 2018 Apr 11.
Results publication: PubMed 28566334Haney DJ, Lock MD, Simon JK, Harris J, Gurwith M. Antibody-Based Correlates of Protection Against Cholera Analysis of a Challenge Study in a Cholera-Naive Population. Clin Vaccine Immunol. 2017 May 31;24(8):e00098-17. doi: 10.1128/CVI.00098-17. Online ahead of print.
Derived from this study: PubMed 31743334Hossain M, Islam K, Kelly M, Mayo Smith LM, Charles RC, Weil AA, Bhuiyan TR, Kovac P, Xu P, Calderwood SB, Simon JK, Chen WH, Lock M, Lyon CE, Kirkpatrick BD, Cohen M, Levine MM, Gurwith M, Leung DT, Azman AS, Harris JB, Qadri F, Ryan ET. Immune responses to O-specific polysaccharide (OSP) in North American adults infected with Vibrio cholerae O1 Inaba. PLoS Negl Trop Dis. 2019 Nov 19;13(11):e0007874. doi: 10.1371/journal.pntd.0007874. eCollection 2019 Nov.
Derived from this study: PubMed 29624592Islam K, Hossain M, Kelly M, Mayo Smith LM, Charles RC, Bhuiyan TR, Kovac P, Xu P, LaRocque RC, Calderwood SB, Simon JK, Chen WH, Haney D, Lock M, Lyon CE, Kirkpatrick BD, Cohen M, Levine MM, Gurwith M, Harris JB, Qadri F, Ryan ET. Anti-O-specific polysaccharide (OSP) immune responses following vaccination with oral cholera vaccine CVD 103-HgR correlate with protection against cholera after infection with wild-type Vibrio cholerae O1 El Tor Inaba in North American volunteers. PLoS Negl Trop Dis. 2018 Apr 6;12(4):e0006376. doi: 10.1371/journal.pntd.0006376. eCollection 2018 Apr.
Individual participant dataSharing planned: No

Related trials for Cholera

Not yet recruitingPhase 2
Ondansetron to Prevent Oral Rehydration Failure in Children With Cholera
Cholera (Disorder)
Not yet recruitingPhase 4
Study on Changes in Gut Microbiota, Inflammatory Factors, and Bowel Habits Following Oral Administration of Recombinant B-subunit/Whole Cell Cholera Vaccine in a Community Population
Bowel Habits, Gut Microbiomes
RecruitingPhase 1
Phase 1b Ascending Dose Study of PanChol in Healthy Volunteers
Cholera Vaccination Reaction
RecruitingPhase 4
CVD 38000: Study of Responses to Vaccination With Typhoid and/or Cholera
Typhoid and/or Cholera Vaccination
Enrolling by invitationPhase 4
A Post-marketing Observational Study of Oral Cholera Vaccine
Diarrhea

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

James McCarty, MD study director

Emergent BioSolutions

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing PXVX0200 in people with Cholera, run by Bavarian Nordic at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

% of Participants With Moderate to Severe Diarrhea (time frame: Ten days after vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01895855, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2023.