Efficacy of B7A BSIgG Against E. Coli Strain B7A Challenge

NCT03040687 | Completed Phase 1 Results

• 1 other identifier: CIR 315 BSIgG
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Healthy Volunteer

Keywords

ETEC; Escherichia coli; enteritis; challenge; CS6; B7A

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  28 days

Study Arms (3)

Anti-CS6 group

EXPERIMENTAL

Anti-CS6 BSIgG and challenge strain CS6-expressing ETEC (B7A)

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)

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)

Biological: Bovine Immunoglobin Negative Control (Lot PD161071NC); Biological: B7A- CS6-expressing ETEC challenge strain

Interventions

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

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• Lactation or breastfeeding.
• 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.
• 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.

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• Naval Medical Research Center: collaborator
• United States Department of Defense: collaborator

Study Sites (1)

Johns Hopkins Center for Immunization Research

Baltimore, Maryland, 21205, United States

Location

Related Publications (3)

• 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.

  PMID: 26938983 BACKGROUND

• McKenzie 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.

  PMID: 21628659 BACKGROUND

• Freedman 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.

  PMID: 9498445 BACKGROUND

MeSH Terms

Conditions

Escherichia coli Infections; Enteritis

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Results Point of Contact

• Title: Kawsar Talaat
• Organization: Johns Hopkins University

ktalaat@jhu.edu

410-502-9627

Study Officials

• Kawsar R Talaat, MD

  Johns Hopkins Center for Immunization Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2017
• First Posted: February 2, 2017
• Study Start: January 1, 2017
• Primary Completion: April 1, 2017
• Study Completion: August 1, 2017
• Last Updated: June 14, 2019
• Results First Posted: June 14, 2019

Record last verified: 2019-03

Locations

US (1)