Conditions: Healthy Volunteer Safety Study
Keywords: sepsis septic shock
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 25
Healthy volunteers: yes

Brief 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.

Arms:
arm 1: AB103 7.5 µg/kg administered as a single IV infusion arm 2: AB103 37.5 µg/kg administered as a single IV infusion arm 3: AB103 150 µg/kg administered as a single IV infusion arm 4: AB103 450 µg/kg administered as a single IV infusion arm 5: Normal saline (0.9% sodium chloride) administered as a single IV infusion

Interventions: intervention 1: AB103 intervention 2: Placebo
Intervention descriptions: intervention 1: 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 intervention 2: Single intravenous infusion of normal saline (0.9% sodium chloride) administered over approximately 10 minutes

Protocol document: