This is a phase 1, randomized, placebo-controlled, blinded study in up to 36 healthy adults, aged 18-45 years, challenged with Enterotoxigenic Escherichia coli, evaluating the safety, tolerability and anti-diarrheal activity of VENBETA6890, an orally administered, human monoclonal IgA.
Part A will consist of 1 sentinel dosing group of 2 subjects randomized 1:1 to receive VENBETA6890 or placebo and will evaluate VENBETA6890 at dose levels of 15 mg/kg. On Day 1, subjects will receive 15 mg/kg in the morning and a second dose of 15 mg/kg 8 - 12 h later in the outpatient clinic. On Day 2, they will receive a third dose of 15 mg/kg at approximately 8 - 12 h after the last dose on Day 1. The occurrence of local and systemic reactogenicity (solicited AEs) over the subsequent 7-days post-dosing will be collected; non-solicited non-serious AEs will be collected through 28-days post-dosing and serious adverse events (SAEs) will be collected through 2 months. An independent Safety Monitoring Committee (SMC) will review the cumulative 7-day safety data for the sentinel group and must approve for the study to proceed to Part B. Part B will consist of a single inpatient cohort of up to 34 subjects who will be randomized 1:1 to receive VENBETA6890 15 mg/kg, or placebo on Day -1 at approximately 12 h pre-challenge, Day 1 at approximately 1 h pre-challenge, and Day 1 at approximately 12 h post-challenge. All subjects will be challenged with wild-type ETEC strain H10407 and will be closely monitored on the inpatient unit for ETEC diarrheal illness. Subjects will receive the 3-day course of antibiotic therapy starting on Day 6 or earlier dependent on symptoms. Discharge from the inpatient unit is contingent upon the absence of ETEC diarrheal illness, including no diarrhea and no fever, plus two sequential negative stool cultures for ETEC separated by at least 12 hours. An SMC will review the cumulative safety data after data collected during the Day 29 visit of the inpatient challenge cohort has been compiled.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
36
Part A will consist of 1 sentinel dosing group of 2 subjects randomized 1:1 to receive VENBETA6890 and will evaluate VENBETA6890 at dose levels of 15 mg/kg. On Day 1, subjects will receive 15 mg/kg in the morning and a second dose of 15 mg/kg 8 - 12 h later in the outpatient clinic. On Day 2, they will receive a third dose of 15 mg/kg at approximately 8 - 12 h after the last dose on Day 1.
Part A Placebo (saline) will be administered at dose levels of 15 mg/kg. On Day 1, subjects will receive 15 mg/kg in the morning and a second dose of 15 mg/kg 8 - 12 h later in the outpatient clinic. On Day 2, they will receive a third dose of 15 mg/kg at approximately 8 - 12 h after the last dose on Day 1.
Pharmaron CPC
Baltimore, Maryland, United States
Number of Participants who Experience Treatment Emergent Adverse Events
The number of participants who experience treatment emergent adverse events. Severity of Treatment Emergent Adverse Events (TEAEs) are determined by changes in vital signs (VS), Physical examination (PE), and routine clinical laboratory tests.
Time frame: up to day 60
Proportion of Participants who experience treatment emergent adverse events.
Severity of Treatment Emergent Adverse Events (TEAEs) are determined by changes in vital signs (VS), Physical examination (PE), and routine clinical laboratory tests.
Time frame: up to 60 days
Number of participants experiencing diarrhea after enterotoxigenic E.coli (ETEC) challenge
This outcome is measuring the number of participants who experience diarrhea after ETEC challenge. DIARRHEA is defined as at least 1 loose stool (stool consistency of Grade 3 or higher per protocol definition) of ≥ 300 g or at least 2 loose stools totaling ≥ 200 g during any 48-hour period
Time frame: 120 hours post challenge
Proportion of participants experiencing diarrhea after ETEC challenge
This outcome is measuring the proportion of participants who experience diarrhea after ETEC challenge. DIARRHEA is defined as at least 1 loose stool (stool consistency of Grade 3 or higher per protocol definition) of ≥ 300 g or at least 2 loose stools totaling ≥ 200 g during any 48-hour period
Time frame: 120 hours post challenge
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