Evaluation of Safety, PK and Immunomodulatory Effects of AB103 in Necrotizing Soft Tissue Infections Patients
- Registration Number
- NCT01417780
- Lead Sponsor
- Atox Bio Ltd
- Brief Summary
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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AB103 0.25 mg/kg AB103 - AB103 0.5 mg/kg AB103 - Placebo Placebo Normal saline (0.9% sodium chloride)
- Primary Outcome Measures
Name Time Method Number of Subjects With One or More Serious Adverse Events (SAEs) 28 days 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.Platelet (PLT) Count Screening and Day 7 Screening PLT results, Day 7 PLT results, and change in PLT from screening to Day 7
International Normalized Ratio (INR) Screening and Day 7 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.
QT Interval With Fridericia's Correction (QTcF) Pre-dose and up to 24 hours post-dose Pre-dose QTcF, post-dose QTcF, change in QTcF from pre-dose to post-dose
Categorical Change in QTcF Pre-dose and up to 24 hours post-dose 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
Number of Subjects With One or More Adverse Events (AEs) During the Treatment Period 7 days 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.
Alanine Aminotransferase (ALT) Screening and Day 7 Screening ALT results, Day 7 ALT results, and change in ALT from screening to Day 7
Aspartate Aminotransferase (AST) Screening and Day 7 Screening AST results, Day 7 AST results, and change in AST from screening to Day 7
Area Under the Plasma Concentration Versus Time Curve (AUC) 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. 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.
Maximum Plasma Concentration (Cmax) 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 (observed)
Alkaline Phosphatase (ALP) Screening and Day 7 Screening ALP results, Day 7 ALP results, and change in ALP from screening to Day 7
Total Bilirubin (Tbili) Screening and Day 7 Screening Tbili results, Day 7 Tbili results, and change in Tbili from screening to Day 7
Serum Creatinine (sCr) Screening and Day 7 Screening sCr results, Day 7 sCr results, and change in sCr from screening to Day 7
Albumin (Alb) Screening and Day 7 Screening Alb results, Day 7 Alb results, and change in Alb from screening to Day 7
Hemoglobin (Hgb) Screening and Day 7 Screening Hgb results, Day 7 Hgb results, and change in Hgb from screening to Day 7
Total White Blood Cell (WBC) Count Screening and Day 7 Screening WBC results, Day 7 WBC results, and change in WBC from screening to Day 7
Apparent Terminal Plasma Half-life (T1/2) 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) is the amount of time for plasma concentrations to decline by 50%.
Clearance (CL) 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) is the volume of plasma completely cleared of drug per unit of time.
Apparent Volume of Distribution Under Steady State Conditions (Vss) 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) based on drug concentration in plasma
- Secondary Outcome Measures
Name Time Method C-reactive Protein (CRP) Screening and Day 7 Screening CRP results, Day 7 CRP results, and change in CRP from screening to Day 7
Day 14 Sequential Organ Failure Assessment (SOFA) Score 14 days 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.Day 14 Sequential Organ Failure Assessment (SOFA) Score Less Than or Equal to 1 14 days 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.
Hospital Length of Stay (LOS) 28 days The duration of hospital stay over the 28-day study period.
Intensive Care Unit-free Days (ICU-free Days) 28 days The number of intensive care unit-free days (ICU-free days)
Ventilator-free Days 28 days The number of ventilator-free days (days without ventilator use)
Trial Locations
- Locations (7)
San Francisco General Hospital
🇺🇸San Francisco, California, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of Southern California Los Angeles
🇺🇸Los Angeles, California, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States