Safety and Efficacy of Bovine Milk Immunoglobulin Against CS17 and CsbD

NCT00524004 | Completed Phase 2

• 3 other identifiers: CIR 233WIRB Approval Number 20062031W81XWH-04-1-0067
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase II, randomized, double-blind, placebo-controlled study designed to investigate whether hyperimmune bovine milk IgG products specific for CsbD and CS17, protect subjects against diarrhea upon challenge with a CS-17-ETEC strain LSN03-016011/A. The study will also evaluate safety and tolerability of these bovine milk IgG products and describe the immune responses following challenge. The primary study objectives are: 1) Assess safety of the anti-CsbD and anti-CS17 bovine milk IgG among healthy adult volunteers when orally administered three times a day over 7 days. 2) Determine efficacy of the anti-CsbD bovine milk IgG preparation against ETEC diarrhea upon challenge with CS17-ETEC, and 3)Determine efficacy of the anti-CS17 bovine milk IgG preparation against ETEC diarrhea upon challenge with CS17-ETEC. A secondary objective is to determine efficacy of the anti-CsbD and anti-CS17 bovine milk IgG preparations against moderate to severe ETEC diarrhea upon challenge with CS17-ETEC.

Conditions

Travelers' Diarrhea

Keywords

Passive immunization, Bovine Milk Immunoglobulin

Outcome Measures

Primary Outcomes (1)

• Prevention of ETEC diarrhea

  120 hours after challenge

Secondary Outcomes (1)

• Prevention of moderate to severe ETEC diarrhea

  120 hours after challenge

Study Arms (3)

Anti-CsbD Bovine IgG

EXPERIMENTAL

Anti CsbD Bovine Milk Immunoglobulin

Other: Placebo; Biological: Anti-CS17 Bovin IgG

Placebo

EXPERIMENTAL

Lacto-free milk supplement

Biological: Anti-CS17 Bovin IgG

Anti-CS17 Bovin IgG

EXPERIMENTAL

Anti-CS17 Bovin Milk Immunoglobulin

Biological: Anti-CsbD Bovine IgG; Biological: Anti-CS17 Bovin IgG

Interventions

Anti-CsbD Bovine IgG BIOLOGICAL

Three times a day for seven days

Also known as: Experimental

Anti-CS17 Bovin IgG

Placebo OTHER

Three times a day for seven days

Also known as: Lacto-Free milk supplement

Anti-CsbD Bovine IgG

Anti-CS17 Bovin IgG BIOLOGICAL

Three times a day for seven days

Also known as: Experimental

Anti-CS17 Bovin IgG; Anti-CsbD Bovine IgG; Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female between 18 and 45 years of age
• General good health, without significant medical illness, abnormal physical exam findings or clinically significant lab abnormalities, as determined by the PI
• Demonstrate comprehension of the protocol procedures and knowledge of ETEC illness by passing a written exam (pass grade ≥ 70%)
• Willing to participate after informed consent obtained
• Available for all planned follow-up visits
• Negative serum pregnancy test at screening; on the day of admission 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 unable to bear children must have this documented (e.g., tubal ligation or hysterectomy).

You may not qualify if:

• Presence of significant medical conditions such as psychiatric conditions, gastrointestinal disease (such as peptic ulcer, active gastritis or gastroesophageal reflux disease, inflammatory bowel disease), alcohol or illicit drug abuse/dependency, or lab abnormalities which in the opinion of the investigator precludes participation in the study
• Immunosuppressive illness or IgA deficiency (below the normal limits)
• Positive serology results for HIV or HCV antibodies, or HBsAg
• Significant abnormalities in screening hematology, serum chemistry, urinalysis or EKG (EKG in subjects ≥ 40 years), as determined by the PI
• Allergy to fluoroquinolones, trimethoprim-sulfamethoxazole, or ampicillin/penicillin (excluded if allergic to 2 of 3)
• Fewer than 3 stools per week or more than 3 stools per day on a regular basis.
• 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 = at least weekly)
• Use of antibiotics during the 7 days before dosing or proton pump inhibitors, H2 blockers, or antacids within 48 hours of dosing (bovine milk IgG).
• Travel to countries where ETEC or cholera infection is endemic (most of the developing world) within 2 years prior to bovine milk IgG dosing
• History of vaccination for or ingestion of ETEC, cholera, or LT toxin.
• Stool culture (collected no more than 1 week prior to admission) positive for ETEC or other bacterial enteric pathogens (including Salmonella, Shigella and Campylobacter)
• Use of any investigational drug or any investigational vaccine within 30 days preceding the first dose of test article/placebo, or planned use during the active study period
• Clinical history of lactose intolerance or allergy to milk or milk products
• Use of any medication known to affect the immune function (e.g., corticosteroids) within 30 days preceding the first dose of test article/placebo, or planned use during the active study period. (Topical and intra-articular steroids will not exclude subjects.)

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• Naval Medical Research Center: collaborator

Study Sites (2)

Center for Immunization Research

Baltimore, Maryland, 21205, United States

Location

Johns Hopkins Bayview Medicial Center, Inpatient Unit

Baltimore, Maryland, 21224, United States

Location

Related Publications (1)

• Savarino SJ, McKenzie R, Tribble DR, Porter CK, O'Dowd A, Sincock SA, Poole ST, DeNearing B, Woods CM, Kim H, Grahek SL, Brinkley C, Crabb JH, Bourgeois AL. Hyperimmune Bovine Colostral Anti-CS17 Antibodies Protect Against Enterotoxigenic Escherichia coli Diarrhea in a Randomized, Doubled-Blind, Placebo-Controlled Human Infection Model. J Infect Dis. 2019 Jul 2;220(3):505-513. doi: 10.1093/infdis/jiz135.

  PMID: 30897198 DERIVED

Study Officials

• Robin McKenzie, M.D.

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist

Study Record Dates

• First Submitted: August 31, 2007
• First Posted: September 3, 2007
• Study Start: January 30, 2007
• Primary Completion: October 26, 2007
• Study Completion: October 26, 2007
• Last Updated: April 5, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)