AB103 Peptide Antagonist in Healthy Volunteers
Condition: Healthy Volunteer Safety Study
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary objective of this study is to establish the safety profile and maximum tolerated
      dose (MTD) of AB103 given as a single intravenous (IV) infusion in healthy volunteers.
    

Detailed description: 
      After consent and establishing eligibility for the study, each subject received a single IV
      infusion of escalating doses of AB103 (7.5, 37.5, 150, 450 μg/kg in 5 subjects at each dose)
      or placebo (n=5). Screening blood chemistry, hematology, coagulation, urinalysis, vital
      signs, and electrocardiogram (ECG) were used to assure medical fitness to participate in the
      study. These measures were repeated during and after treatment with AB103 to monitor for
      adverse events (AEs). ECG and pulse oximetry was monitored continuously starting 15 minutes
      before the infusion and for 2 hours after each infusion. Vital signs (sitting blood pressure,
      temperature, heart rate, respiratory rate, and pulse oximetry) and ECG measurements were
      recorded every 15 minutes for the first two hours starting from the beginning of the infusion
      and then approximately 24 hours later. Blood chemistry, hematology, coagulation, and
      urinalysis, were repeated one day and one week after infusions. AEs either observed by the
      investigator or reported spontaneously by the subjects were recorded at each study visit.
      Subjects kept a 7-day diary starting on the day of infusion to record any AEs. The primary
      basis on which escalation was based was dose limiting toxicities (DLTs) defined as the
      emergence of one or more selected AEs that reached a threshold which justified stopping the
      trial. After safety monitoring committee review of safety data, progression to the next
      cohort was to occur as follows:

        1. If none of the 5 AB103 subjects in a cohort experienced a non-extreme DLT, escalation to
           the next dose cohort was to occur.

        2. If 1 of 5 subjects receiving AB103 in a cohort experienced a non-extreme DLT, then a
           total of 8 subjects (6 active: 2 placebo) were to be enrolled in that cohort before
           escalating to the next dose (escalation will only occur if no additional subjects (2
           total) have a non-extreme DLT).

        3. If there were 0/6 or 1/6 active subjects with a non-extreme DLT at the highest dose, the
           highest dose was to be considered the MTD. If there were 2/6 active subjects with a
           non-extreme DLT in a cohort, then the next lowest dose was to be considered the MTD.

        4. If an extreme DLT occurred, the study was to be halted immediately.

      Subjects in Cohorts #1 to #3 had a blood sample (40 milliliters, mL) drawn pre-infusion, 24
      hours after the infusion (Day 2), and a final sample at the Day 6-8 clinic visit (total of
      120 mL) for leukocyte phenotyping by flow cytometry. Subjects in Cohort #4 had a blood sample
      (40 mL) drawn pre-infusion, 1 hour after the infusion, and a final sample at the Day 6-8
      clinic visit (total of 120 mL) for leukocyte phenotyping by flow cytometry.

      For the pharmacokinetic (PK) analysis, blood was collected at the mid-point of the infusion
      and 1, 2, 5, 10, 20, 30, and 60 minutes and approximately 24 hours post-infusion, and plasma
      was isolated for quantitation of AB103 peptide concentrations.
    

Intervention name(s): AB103; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Single intravenous infusion at doses of 7.5 µg/kg, 37.5 µg/kg, 150 µg/kg, or 450 µg/kg administered over approximately 10 minutes; Single intravenous infusion of normal saline (0.9% sodium chloride) administered over approximately 10 minutes
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: sepsis; septic shock