A study to evaluate the safety and pharmacokinetics profile of different doses of AB103 administered to patients diagnosed with Necrotizing Soft Tissue Infections that are scheduled for an urgent surgical intervention as part of their standard of care.
A study to evaluate the safety and pharmacokinetics profile of different doses of AB103 administered to patients diagnosed with Necrotizing Soft Tissue Infections that are scheduled for an urgent surgical intervention as part of their standard of care. The primary study hypothesis is that AB-103 can be administered safely to the patients presenting with Necrotizing Soft Tissue Infections. Secondary endpoints are efficacy by exploratory descriptive analyses of specific efficacy endpoints from three outcome domains to demonstrate treatment benefit of AB103 in comparison to placebo in patients with Necrotizing Soft Tissue Infections. The efficacy domains are: 1. Clinical status domain 2. Pharmacoeconomics domain 3. Systemic and local inflammatory biomarker domain
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
43
University of Southern California Los Angeles
Los Angeles, California, United States
San Francisco General Hospital
San Francisco, California, United States
University of Florida
Gainesville, Florida, United States
University of Maryland Medical Center
Baltimore, Maryland, United States
Number of Subjects With One or More Adverse Events (AEs) During the Treatment Period
An AE is any untoward medical occurrence in a subject administered study drug and that does not necessarily have a causal relationship with the study drug. An AE could therefore be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug.
Time frame: 7 days
Number of Subjects With One or More Serious Adverse Events (SAEs)
A serious adverse event (SAE) is an AE occurring during any study phase and at any dose of the study drug (AB103 or placebo) that fulfills one or more of the following criteria: * Results in death * Is life-threatening (i.e., the subject was, in the opinion of the Investigator, at immediate risk of death from the event as it occurred) * Requires or prolongs hospitalization * Results in persistent or significant disability or incapacity (i.e., the event causes a substantial disruption of a person's ability to conduct normal life functions) * Is a congenital anomaly or birth defect, or * Is an important and significant medical event.
Time frame: 28 days
Alanine Aminotransferase (ALT)
Screening ALT results, Day 7 ALT results, and change in ALT from screening to Day 7
Time frame: Screening and Day 7
Aspartate Aminotransferase (AST)
Screening AST results, Day 7 AST results, and change in AST from screening to Day 7
Time frame: Screening and Day 7
Alkaline Phosphatase (ALP)
Screening ALP results, Day 7 ALP results, and change in ALP from screening to Day 7
Time frame: Screening and Day 7
Total Bilirubin (Tbili)
Screening Tbili results, Day 7 Tbili results, and change in Tbili from screening to Day 7
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Oregon Health and Science University
Portland, Oregon, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Harborview Medical Center
Seattle, Washington, United States
Time frame: Screening and Day 7
Serum Creatinine (sCr)
Screening sCr results, Day 7 sCr results, and change in sCr from screening to Day 7
Time frame: Screening and Day 7
Albumin (Alb)
Screening Alb results, Day 7 Alb results, and change in Alb from screening to Day 7
Time frame: Screening and Day 7
Hemoglobin (Hgb)
Screening Hgb results, Day 7 Hgb results, and change in Hgb from screening to Day 7
Time frame: Screening and Day 7
Total White Blood Cell (WBC) Count
Screening WBC results, Day 7 WBC results, and change in WBC from screening to Day 7
Time frame: Screening and Day 7
Platelet (PLT) Count
Screening PLT results, Day 7 PLT results, and change in PLT from screening to Day 7
Time frame: Screening and Day 7
International Normalized Ratio (INR)
Screening INR results, Day 7 INR results, and change in INR from screening to Day 7. In general, the higher the INR value, the longer it takes for blood to form a clot.
Time frame: Screening and Day 7
QT Interval With Fridericia's Correction (QTcF)
Pre-dose QTcF, post-dose QTcF, change in QTcF from pre-dose to post-dose
Time frame: Pre-dose and up to 24 hours post-dose
Categorical Change in QTcF
Number and percentage of patients with a change in QTcF of \> 30 msec; number and percentage of patients with a change in QTcF of \> 60 msec
Time frame: Pre-dose and up to 24 hours post-dose
Area Under the Plasma Concentration Versus Time Curve (AUC)
Area under the plasma concentration versus time curve (AUC) from time zero to infinity following a single dose of study drug, obtained by noncompartmental methods. It is an integrated measure of study drug plasma exposure.
Time frame: Prior to infusion, at mid infusion time, end of infusion, and at 2, 5, 10, 20, 30, 60 min and 120 minutes after completion of the IV infusion of study drug.
Maximum Plasma Concentration (Cmax)
Maximum plasma concentration (observed)
Time frame: Prior to infusion, at mid infusion time, end of infusion, and at 2, 5, 10, 20, 30, 60 min and 120 minutes after completion of the IV infusion of study drug.
Apparent Terminal Plasma Half-life (T1/2)
Apparent terminal plasma half-life (T1/2) is the amount of time for plasma concentrations to decline by 50%.
Time frame: Prior to infusion, at mid infusion time, end of infusion, and at 2, 5, 10, 20, 30, 60 min and 120 minutes after completion of the IV infusion of study drug.
Clearance (CL)
Clearance (CL) is the volume of plasma completely cleared of drug per unit of time.
Time frame: Prior to infusion, at mid infusion time, end of infusion, and at 2, 5, 10, 20, 30, 60 min and 120 minutes after completion of the IV infusion of study drug.
Apparent Volume of Distribution Under Steady State Conditions (Vss)
Apparent volume of distribution under steady state conditions (Vss) based on drug concentration in plasma
Time frame: Prior to infusion, at mid infusion time, end of infusion, and at 2, 5, 10, 20, 30, 60 min and 120 minutes after completion of the IV infusion of study drug.
C-reactive Protein (CRP)
Screening CRP results, Day 7 CRP results, and change in CRP from screening to Day 7
Time frame: Screening and Day 7
Day 14 Sequential Organ Failure Assessment (SOFA) Score
Day 14 SOFA score is the sum of individual SOFA score components at Day 14. Results include last observation carried forward (LOCF) imputation for missing values. SOFA total scores range from 0 to 24, with higher scores reflecting a worse clinical status or outcome. A SOFA total score of 0 or 1 reflects resolution of organ dysfunction/failure.
Time frame: 14 days
Day 14 Sequential Organ Failure Assessment (SOFA) Score Less Than or Equal to 1
Number and percentage of patients with Day 14 Sequential Organ Failure Assessment (SOFA) score less than or equal to 1. SOFA total scores range from 0 to 24, with higher scores reflecting a worse clinical status or outcome. A SOFA total score of 0 or 1 reflects resolution of organ dysfunction/failure.
Time frame: 14 days
Hospital Length of Stay (LOS)
The duration of hospital stay over the 28-day study period.
Time frame: 28 days
Intensive Care Unit-free Days (ICU-free Days)
The number of intensive care unit-free days (ICU-free days)
Time frame: 28 days
Ventilator-free Days
The number of ventilator-free days (days without ventilator use)
Time frame: 28 days