Safety and Efficacy of Bovine Milk Immunoglobulin Against CS17 and CsbD
Condition: Travelers' Diarrhea
MeSH terms: Diarrhea
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      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.

      STUDY DESIGN 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.

      Subjects (N=39) will be randomized into three groups receiving anti-CS17 bovine milk IgG,
      anti-CsbD bovine milk IgG, or a placebo control (a commercially available lactose-free infant
      formula called LactoFree® Lipil®) on study day -2. Subjects will receive three doses a day of
      the test article 15 minutes (range 10 - 25 minutes) after each of their three daily meals
      (breakfast, lunch and dinner) for a period of 7 days (i.e., from study day -2 to study day
      4). The study will be divided into two cohorts, An initial cohort of 9 subjects (3 per
      treatment group), will be admitted to the General Clinical Research Center (GCRC) of the
      Johns Hopkins Hospital for the initial testing of the bovine milk IgG products. A second
      cohort of 30 subjects will then be admitted to the Bayview inpatient facility to complete the
      prophylaxis study. Logistical considerations and/or withdrawals or disqualifications prior to
      admission or after randomization, but prior to receiving the ETEC challenge, may require a
      third cohort to be admitted to either of these facilities. Allowing for these contingencies,
      the minimum number of subjects to be challenged with ETEC is 33 total and the maximum number
      of subjects will be 42. The GCRC Project Review Committee will review the protocol prior to
      subject admission at the GCRC. A brief description of the two inpatient facilities to be used
      in this study is provided in Section 6.1.2. Unit doses of the test article powders (as
      detailed in Table 5) will be suspended in 150 mL of water containing 2 grams of sodium
      bicarbonate buffer. Doses of the test articles/placebo will be prepared by study staff under
      the supervision of the research pharmacist. The study staff involved in dose preparation will
      not be collecting clinical data on subjects. On the fourth day of the inpatient phase (study
      day 0), after their morning meal and receipt of test article/placebo, subjects will be given
      120mL of sodium bicarbonate buffer to neutralize their stomach acidity. About 1 minute later
      they will ingest a dose of CS17-ETEC strain LSN03-016011/A (5 X 109 cfu) diluted in 30 ml
      sodium bicarbonate buffer. Subjects will continue to receive three doses a day of the test
      articles/placebo until study day 4. Subjects meeting preset criteria will be treated with
      antibiotics within 24 hours of determination by the investigator and test article/placebo
      administration will be discontinued with initiation of treatment. Subjects who do not receive
      early antibiotic treatment will start antibiotic treatment on study day 5. Routine discharge
      is scheduled for day 7, when most subjects are expected to meet the discharge criteria of:
      they feel well(clinical symptoms resolved or resolving and have taken at least one dose of
      antibiotic and have 1 stool culture negative for the challenge strain. Subjects may be
      discharged earlier than day 7 on a case-by-case basis if they meet discharge criteria. The
      duration of the active study period is approximately seven months, encompassing up to 6 and
      1/2 weeks of screening/enrollment, 4 weeks of the inpatient/outpatient phase when data and
      samples will be collected, 12 weeks for immunology assays, and 2 months for analysis and
      report.
    

Intervention name(s): Anti-CsbD Bovine IgG; Placebo; Anti-CS17 Bovin IgG
Intervention type(s): Biological; Other; Biological
Intervention description(s): Three times a day for seven days; Three times a day for seven days; Three times a day for seven days
Other intervention name(s): Experimental; Lacto-Free milk supplement; Experimental
Intervention MeSH terms: Immunoglobulin G
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Passive immunization, Bovine Milk Immunoglobulin