Healthy VolunteerPhase 1NCT03040687
Efficacy of B7A BSIgG Against E. Coli Strain B7A Challenge
A Phase 1 study testing Anti CS6 BSIgG product (Lot PD1601105CS), Anti B7A BSIgG product (Lot PD1601132ET) and B7A- CS6-expressing ETEC challenge strain in people with Healthy Volunteer, run by Johns Hopkins Bloomberg School of Public Health at 1 site in United States.
Trial summary
Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea worldwide. Vaccines and therapeutics are under development to prevent ETEC disease in children and travelers. One approach is to use passive protection (antibodies) to prevent infection. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer
- What is being tested?
- Anti CS6 BSIgG product (Lot PD1601105CS), Anti B7A BSIgG product (Lot PD1601132ET) and B7A- CS6-expressing ETEC challenge strain
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to Aug 2017
- Phase
- Phase 1
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female between 18 and 50 years of age, inclusive.
- General good health, without significant medical illness, abnormal physical examination findings or clinical laboratory abnormalities as determined by principal investigator (PI) or PI in consultation with the research monitor and sponsor.
- Demonstrate comprehension of the protocol procedures and knowledge of ETEC illness by passing a written examination (pass grade ≥ 70%)
- Willing to participate after informed consent obtained.
- Available for all planned follow-up visits.
- Negative serum pregnancy test at screening and negative serum and/or urine pregnancy test on the day of admittance to the inpatient phase for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female subjects unable to bear children must have this documented (e.g., tubal ligation or hysterectomy).
Who cannot join
- General health criteria
- Presence of a significant medical condition, (e.g. psychiatric conditions or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease, alcohol or illicit drug abuse/dependency, or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study.
- Immunosuppressive illness or Immunoglobulin A (IgA) deficiency (serum IgA < 7 mg/dL or below the limit of detection of assay)
- Evidence of confirmed infection with HIV, HBsAg, or Hepatitis C Virus (HCV), with confirmatory assays.
- Use of any investigational product within 30 days preceding the receipt of the investigational products, or planned use during the active study period
- Significant abnormalities in screening lab hematology or serum chemistries, as determined by PI or PI in consultation with the research monitor and sponsor.
Show all 19Show fewer
- Lactation or breastfeeding.
- Research-related exclusions applicable to challenge
- History of microbiologically confirmed ETEC or cholera infection in last 3 years.
- Occupation involving handling of ETEC or Vibrio cholerae currently, or in the past 3 years.
- Travel to countries where ETEC or cholera infection is endemic (most of the developing world) within 3 years prior to dosing.
- Symptoms consistent with Travelers' Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within 3 years prior to dosing, OR planned travel to endemic countries during the length of the study.
- Vaccination for or ingestion of ETEC, cholera, or E coli heat labile toxin within 3 years prior to dosing.
- Any prior experimental infection with ETEC strain B7A.
- Study-specific Exclusion Criteria (potential increased risk or complicating outcome ascertainment)
- Abnormal stool pattern (fewer than 3 per week or more than 3 per day).
- History of diarrhea in the 2 weeks prior to planned inpatient phase.
- Regular use of laxatives, antacids, or other agents to lower stomach acidity (regular defined as at least weekly).
- Use of antibiotics during the 7 days before receipt of any investigational
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Center for Immunization Research
Baltimore, Maryland, 21205
About this study
Official title: Protective Efficacy of Orally Delivered Bovine Serum Immunoglobulin (BSIgG) Specific for the Colonization Factor CS6 Following Challenge With the CS6-expressing Enterotoxigenic E. Coli (ETEC) Strain B7A
Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea worldwide. Vaccines and therapeutics are under development to prevent ETEC disease in children and travelers. One approach is to use passive protection (antibodies) to prevent infection. The purpose of this study are to assess the safety of serum-derived bovine immunoglobulins in healthy adult subjects when orally administered and to estimate protective efficacy of those preparations against moderate-severe diarrhea upon challenge with the ETEC strain B7A.
Read the detailed description
Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of infectious diarrhea in children in resource limited countries, and is also a frequent cause of traveler's diarrhea in civilian and military travelers to endemic countries. ETEC strains express a variety of colonization factors (CF) that help them attach to the intestinal wall. Each colonization factor has one or more surface antigens (CS). One of the major surface antigens of ETEC is CS6 (Coli surface antigen 6).
Vaccines and treatments to prevent ETEC disease are under development. Some of these target specific enterotoxins or colonization factors. For over 40 years, we have used ETEC human challenge studies to understand the ETEC disease process, immune response, and more recently, to determine whether treatments or vaccines are protective or effective in mitigating disease. B7A is the only CS6 expressing ETEC challenge strain currently used.
A modality that has shown some success in the prevention of diarrhea is passive, oral administration of bovine milk IgG with specific activity against viral, bacterial and parasitic enteropathogens. Passive oral administration of Bovine Serum Immunoglobulins (BSIgG) may protect against ETEC-mediated infectious diarrhea. The hypothesized mechanism of protection stems from the passive administration of bovine anti-tip adhesion or fimbriae antibodies preventing their adherence in the human small intestine (the initial step in pathogenesis), thereby preventing downstream pathogenic processes and symptomatic illness. This study will establish the foundation for evaluating BSIgG products against numerous ETEC CFs.
This study will explore if anti-B7A and anti- CS6 BSIgG provides protection against oral challenge with B7A in healthy adult volunteers. There will be two inpatient admissions of approximately 30 subjects (up to 60 total). They will receive one of three investigational products (IP) three times daily following meals beginning 2 days prior to challenge. Each volunteer will be challenged with CS6 expressing ETEC B7A on Day 0. The investigational product/placebo will be administered for a total of 7 days, or until antibiotic treatment has been administered. The investigators hypothesize that anti-CS6 BSIgG will provide protection against B7A mediated moderate to severe diarrhea upon challenge.
- Conditions
- Healthy Volunteer
- Being tested
- Anti CS6 BSIgG product (Lot PD1601105CS), Anti B7A BSIgG product (Lot PD1601132ET), Bovine Immunoglobin Negative Control (Lot PD161071NC), B7A- CS6-expressing ETEC challenge strain
- Keywords
- ETEC, Escherichia coli, enteritis, challenge, CS6, B7A
- Medical subject headings
- Escherichia coli Infections, Enteritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti CS6 BSIgG product (Lot PD1601105CS)Biological
Anti B7A BSIgG product (Lot PD1601132ET)Biological
Bovine Immunoglobin Negative Control (Lot PD161071NC)Biological
B7A- CS6-expressing ETEC challenge strainBiological
| Study group | Role | What they receive |
|---|---|---|
| Anti-CS6 group | Experimental | Anti-CS6 BSIgG and challenge strain CS6-expressing ETEC (B7A) Receives: Biological: Anti CS6 BSIgG product (Lot PD1601105CS); Biological: B7A- CS6-expressing ETEC challenge strain |
| Anti-whole cell B7A | Experimental | Anti- whole cell B7A (killed) BSIgG and challenge strain CS6-expressing ETEC (B7A) Receives: Biological: Anti B7A BSIgG product (Lot PD1601132ET); Biological: B7A- CS6-expressing ETEC challenge strain |
| control Immunoglobulin group | Experimental | Negative Control (Nonhyperimmune BSIgG placebo) and challenge strain CS6-expressing ETEC (B7A) Receives: Biological: Bovine Immunoglobin Negative Control (Lot PD161071NC); Biological: B7A- CS6-expressing ETEC challenge strain |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Serum Derived Bovine Immunoglobulins (BSIgG)
Number of Participants with adverse events in groups receiving B7A- and CS6- hyperimmune (BSIgG) compared with the group receiving the nonhyperimmune product.
Measured: 28 days
Efficacy of B7A and CS6- Hyperimmune Bovine Serum Immunoglobin to Protect Against Moderate to Severe Diarrhea After Challenge With the CS6 Expressing ETEC Strain B7A
Comparison of the number and percentage of volunteers in the arms receiving the B7A- and CS6 BSIgG vs the arm receiving the nonhyperimmune BSIgG who develop moderate to severe diarrhea.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2017 (estimated)
- Study startJan 2017
- Primary completionApr 2017
- Study completionAug 2017
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 (3)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteerStudies of the same condition, open and under way.
- More trials run by Johns Hopkins Bloomberg School of Public HealthThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins Bloomberg School of Public Health
- Sponsor type
- University, hospital or other
- Collaborators
- Naval Medical Research Center, United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Kawsar R Talaat, MD, Principal investigator, Johns Hopkins Center for Immunization Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03040687
- Sponsor's protocol ID
- CIR 315 BSIgG
- Status last verified
- Mar 2019
- First submitted
- 26 Jan 2017
- Last updated
- 14 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Porter CK, Riddle MS, Alcala AN, Sack DA, Harro C, Chakraborty S, Gutierrez RL, Savarino SJ, Darsley M, McKenzie R, DeNearing B, Steinsland H, Tribble DR, Bourgeois AL. An Evidenced-Based Scale of Disease Severity following Human Challenge with Enteroxigenic Escherichia coli. PLoS One. 2016 Mar 3;11(3):e0149358. doi: 10.1371/journal.pone.0149358. eCollection 2016.
PubMed 26938983McKenzie R, Porter CK, Cantrell JA, Denearing B, O'Dowd A, Grahek SL, Sincock SA, Woods C, Sebeny P, Sack DA, Tribble DR, Bourgeois AL, Savarino SJ. Volunteer challenge with enterotoxigenic Escherichia coli that express intestinal colonization factor fimbriae CS17 and CS19. J Infect Dis. 2011 Jul 1;204(1):60-4. doi: 10.1093/infdis/jir220.
PubMed 21628659Freedman DJ, Tacket CO, Delehanty A, Maneval DR, Nataro J, Crabb JH. Milk immunoglobulin with specific activity against purified colonization factor antigens can protect against oral challenge with enterotoxigenic Escherichia coli. J Infect Dis. 1998 Mar;177(3):662-7. doi: 10.1086/514227.
PubMed 9498445
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protective Efficacy of Orally Delivered Bovine Serum Immunoglobulin (BSIgG) Specific for the Colonization Factor CS6 Following Challenge With the CS6-expressing Enterotoxigenic E. Coli (ETEC) Strain B7A
- ClinicalTrials.gov ID
- NCT03040687
- Acronym / sponsor ID
- CIR 315 BSIgG
- Conditions
- Healthy Volunteer
- Keywords
- ETEC, Escherichia coli, enteritis, challenge, CS6, B7A
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Johns Hopkins Bloomberg School of Public HealthUniversity, hospital or other
- Collaborators
- Naval Medical Research Center, United States Department of Defense
- Study start
- Jan 2017 (actual)
- Primary completion
- Apr 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 2 Feb 2017 (estimated)
- Results
- Posted 14 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea worldwide. Vaccines and therapeutics are under development to prevent ETEC disease in children and travelers. One approach is to use passive protection (antibodies) to prevent infection. The purpose of this study are to assess the safety of serum-derived bovine immunoglobulins in healthy adult subjects when orally administered and to estimate protective efficacy of those preparations against moderate-severe diarrhea upon challenge with the ETEC strain B7A.
Detailed description
Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of infectious diarrhea in children in resource limited countries, and is also a frequent cause of traveler's diarrhea in civilian and military travelers to endemic countries. ETEC strains express a variety of colonization factors (CF) that help them attach to the intestinal wall. Each colonization factor has one or more surface antigens (CS). One of the major surface antigens of ETEC is CS6 (Coli surface antigen 6).
Vaccines and treatments to prevent ETEC disease are under development. Some of these target specific enterotoxins or colonization factors. For over 40 years, we have used ETEC human challenge studies to understand the ETEC disease process, immune response, and more recently, to determine whether treatments or vaccines are protective or effective in mitigating disease. B7A is the only CS6 expressing ETEC challenge strain currently used.
A modality that has shown some success in the prevention of diarrhea is passive, oral administration of bovine milk IgG with specific activity against viral, bacterial and parasitic enteropathogens. Passive oral administration of Bovine Serum Immunoglobulins (BSIgG) may protect against ETEC-mediated infectious diarrhea. The hypothesized mechanism of protection stems from the passive administration of bovine anti-tip adhesion or fimbriae antibodies preventing their adherence in the human small intestine (the initial step in pathogenesis), thereby preventing downstream pathogenic processes and symptomatic illness. This study will establish the foundation for evaluating BSIgG products against numerous ETEC CFs.
This study will explore if anti-B7A and anti- CS6 BSIgG provides protection against oral challenge with B7A in healthy adult volunteers. There will be two inpatient admissions of approximately 30 subjects (up to 60 total). They will receive one of three investigational products (IP) three times daily following meals beginning 2 days prior to challenge. Each volunteer will be challenged with CS6 expressing ETEC B7A on Day 0. The investigational product/placebo will be administered for a total of 7 days, or until antibiotic treatment has been administered. The investigators hypothesize that anti-CS6 BSIgG will provide protection against B7A mediated moderate to severe diarrhea upon challenge.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Anti-CS6 group | Experimental | Biological: Anti CS6 BSIgG product (Lot PD1601105CS), Biological: B7A- CS6-expressing ETEC challenge strainAnti-CS6 BSIgG and challenge strain CS6-expressing ETEC (B7A) |
| Anti-whole cell B7A | Experimental | Biological: Anti B7A BSIgG product (Lot PD1601132ET), Biological: B7A- CS6-expressing ETEC challenge strainAnti- whole cell B7A (killed) BSIgG and challenge strain CS6-expressing ETEC (B7A) |
| control Immunoglobulin group | Experimental | Biological: Bovine Immunoglobin Negative Control (Lot PD161071NC), Biological: B7A- CS6-expressing ETEC challenge strainNegative Control (Nonhyperimmune BSIgG placebo) and challenge strain CS6-expressing ETEC (B7A) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Male or female between 18 and 50 years of age, inclusive.
- General good health, without significant medical illness, abnormal physical examination findings or clinical laboratory abnormalities as determined by principal investigator (PI) or PI in consultation with the research monitor and sponsor.
- Demonstrate comprehension of the protocol procedures and knowledge of ETEC illness by passing a written examination (pass grade ≥ 70%)
- Willing to participate after informed consent obtained.
- Available for all planned follow-up visits.
Key exclusion criteria (19 listed)
- General health criteria
- Presence of a significant medical condition, (e.g. psychiatric conditions or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease, alcohol or illicit drug abuse/dependency, or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study.
- Immunosuppressive illness or Immunoglobulin A (IgA) deficiency (serum IgA < 7 mg/dL or below the limit of detection of assay)
- Evidence of confirmed infection with HIV, HBsAg, or Hepatitis C Virus (HCV), with confirmatory assays.
- Use of any investigational product within 30 days preceding the receipt of the investigational products, or planned use during the active study period
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 |
|---|---|---|
| Anti CS6 BSIgG product (Lot PD1601105CS) | Biological | Anti-CS6 group |
| Anti B7A BSIgG product (Lot PD1601132ET) | Biological | Anti-whole cell B7A |
| Bovine Immunoglobin Negative Control (Lot PD161071NC) | Biological | control Immunoglobulin group |
| B7A- CS6-expressing ETEC challenge strain | Biological | Anti-CS6 group, Anti-whole cell B7A, control Immunoglobulin group |
Primary outcome
Safety of Serum Derived Bovine Immunoglobulins (BSIgG)
Time frame: 28 days
Number of Participants with adverse events in groups receiving B7A- and CS6- hyperimmune (BSIgG) compared with the group receiving the nonhyperimmune product.
Efficacy of B7A and CS6- Hyperimmune Bovine Serum Immunoglobin to Protect Against Moderate to Severe Diarrhea After Challenge With the CS6 Expressing ETEC Strain B7A
Time frame: 28 days
Comparison of the number and percentage of volunteers in the arms receiving the B7A- and CS6 BSIgG vs the arm receiving the nonhyperimmune BSIgG who develop moderate to severe diarrhea.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26938983Porter CK, Riddle MS, Alcala AN, Sack DA, Harro C, Chakraborty S, Gutierrez RL, Savarino SJ, Darsley M, McKenzie R, DeNearing B, Steinsland H, Tribble DR, Bourgeois AL. An Evidenced-Based Scale of Disease Severity following Human Challenge with Enteroxigenic Escherichia coli. PLoS One. 2016 Mar 3;11(3):e0149358. doi: 10.1371/journal.pone.0149358. eCollection 2016.
- Background: PubMed 21628659McKenzie R, Porter CK, Cantrell JA, Denearing B, O'Dowd A, Grahek SL, Sincock SA, Woods C, Sebeny P, Sack DA, Tribble DR, Bourgeois AL, Savarino SJ. Volunteer challenge with enterotoxigenic Escherichia coli that express intestinal colonization factor fimbriae CS17 and CS19. J Infect Dis. 2011 Jul 1;204(1):60-4. doi: 10.1093/infdis/jir220.
- Background: PubMed 9498445Freedman DJ, Tacket CO, Delehanty A, Maneval DR, Nataro J, Crabb JH. Milk immunoglobulin with specific activity against purified colonization factor antigens can protect against oral challenge with enterotoxigenic Escherichia coli. J Infect Dis. 1998 Mar;177(3):662-7. doi: 10.1086/514227.
- Individual participant dataSharing planned: Undecided
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Screening Protocol
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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.
Kawsar R Talaat, MD principal investigator
Johns Hopkins Center for Immunization Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Anti CS6 BSIgG product (Lot PD1601105CS), Anti B7A BSIgG product (Lot PD1601132ET) and B7A- CS6-expressing ETEC challenge strain in people with Healthy Volunteer, run by Johns Hopkins Bloomberg School of Public Health at 1 site 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 6 inclusion and 19 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 14 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 14 Jun 2019). 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?
Safety of Serum Derived Bovine Immunoglobulins (BSIgG) (time frame: 28 days). 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 NCT03040687, which also lists 3 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 14 Jun 2019.