Purpose

The purpose of this study is to determine whether AB103 is safe and effective in the treatment of patients with necrotizing soft tissue infections receiving standard of care therapy.

Conditions

Eligibility

Eligible Ages
Over 12 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Surgical confirmation of NSTI by attending surgeon;
  2. mSOFA score ≥3 (in any one or combination of the 5 major components of SOFA score with one organ component having a score of at least 2: cardiovascular, respiratory, renal, coagulation, CNS), measured as close as possible to the first debridement;
  3. IV drug administration within 6 hours from the clinical diagnosis and the decision at the study site, to have an urgent surgical exploration and debridement (drug should not be administered until surgical confirmation is established);
  4. If a woman is of childbearing potential, she must consistently use an acceptable method of contraception from baseline through Day 28;
  5. If a male patient's sexual partner is of childbearing potential, the male patient must acknowledge that they will consistently use an acceptable method of contraception (defined above) from baseline through Day 28.
  6. Signed and dated ICF as defined by the IRB and, if applicable, California Bill of Rights. If patient is unable to comprehend or sign the ICF, patient's legally acceptable representative may sign the ICF

Exclusion Criteria

  1. BMI>51;
  2. Patient who has been operated at least once for the current NSTI infection and had a curative deep tissue debridement;
  3. Patients with overt peripheral vascular disease in the involved area ;
  4. Diabetic patients with peripheral vascular disease who present with below the ankle infection;
  5. Removed DVT in area of NSTI as an exclusion criteria
  6. Patient with burn wounds;
  7. Current condition of: (a) Inability to maintain a mean arterial pressure > 50 mmHg and/or systolic blood pressure > 70 mmHg for at least 1 hour prior to screening despite the presence of vasopressors and IV fluids or (b) a patient with respiratory failure such that an SaO2 of 80% cannot be achieved or (c) a patient with refractory coagulopathy (INR >5) or thrombocytopenia (platelet count <20,000) that does not partially correct with administration of appropriate factors or blood products;
  8. Chronic neurological impairment that leads to a neuro mSOFA component ≥2;
  9. Recent cerebrovascular accident in the last 3 months;
  10. Patients with cardiac arrest requiring cardiopulmonary resuscitation within the past 30 days;
  11. Patient is not expected to survive throughout 28 days of study due to underlying medical condition, such as poorly controlled neoplasm;
  12. Patient or patient's family are not committed to aggressive management of the patient's condition;
  13. Any concurrent medical condition, which in the opinion of the Investigator, may compromise the safety of the patient or the objectives of the study or the patient will not benefit from treatment such as:
  14. CHF {NYHA class III-IV}
  15. Severe COPD
  16. Liver dysfunction {Childs-Pugh class C}
  17. Immunosuppression (see Appendix F, Section 15.6 for list of excluded immunosuppressive medications)
  18. Neutropenia < 1,000 cells/mm3not due to the underlying infection
  19. Idiopathic Thrombocytopenia Purpura
  20. Receiving or about to receive chemotherapy or biologic anti-cancer treatment although hormonal manipulation therapies for breast and prostate malignancies are permitted
  21. Hematological and lymphatic malignancies in the last 5 years;
  22. Known HIV infection with CD4 count < 200 cells/mm3 or < 14% of all lymphocytes;
  23. Patients with known chronic kidney disease (documented pre-illness creatinine value(s) ≥2.0) or patients receiving renal replacement therapy for chronic kidney disease;
  24. Patients that are treated with continuous hemofiltration (e.g. Continuous Veno-Venous Hemofiltration) for acute kidney dysfunction, not due to NSTI, starting prior to study drug administration;
  25. Pregnant or lactating women;
  26. Previous enrollment in a clinical trial involving investigational drug or a medical device within 30 days;
  27. Previous enrollment in this protocol, ATB-202 or the Phase 2 trial of AB103, ATB-201.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
AB103 0.5 mg/kg
AB103 0.5 mg/kg, IV, single dose
  • Drug: AB103 0.5 mg/kg
    Other names:
    • p2TA
Placebo Comparator
NaCl 0.9%
NaCl 0.9%, IV, single dose
  • Other: NaCl 0.9%
    Other names:
    • Normal saline

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35294

Maricopa Medical Center
Phoenix, Arizona 85008

Banner University Medical Center
Tucson, Arizona 24857

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205

Loma Linda University Medical Center
Loma Linda, California 92354

Keck Hospital of USC
Los Angeles, California 90033

University of Southern California-LAC+USC Medical Center
Los Angeles, California 90033

Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center
Los Angeles, California 90502

University of California, Irvine Medical Center
Orange, California 92868

University of California, Davis Medical Center
Sacramento, California 95817

UCSD Medical Center
San Diego, California 92103

UCH-Memorial Health System
Colorado Springs, Colorado 80909

University of Colorado Hospital
Denver, Colorado 80045

Denver Health Medical Center
Denver, Colorado 80204

Yale New Haven Hospital
New Haven, Connecticut 06520

Washington Hospital Center
Washington, District of Columbia 20010

UF Health Shands Hospital
Gainesville, Florida 32610

Ryder Trauma Center/Jackson Memorial Hospital
Miami, Florida 33136

Emory University at Grady Memorial Hospital
Atlanta, Georgia 30303

University of Iowa Hospital and Clinics
Iowa City, Iowa 52242

University of Kentucky
Lexington, Kentucky 40536

Our Lady of the Lake Regional Medical Center
Baton Rouge, Louisiana 70808

Baton Rouge General Hospital
Baton Rouge, Louisiana 70809

LSU Health Science Center
New Orleans, Louisiana 70112

Maine Medical Center
Portland, Maine 04102

University of Maryland R Adams Cowley Shock Trauma Center
Baltimore, Maryland 21201

Massachusetts General Hospital
Boston, Massachusetts 02114

Brigham and Women's Hospital
Boston, Massachusetts 02115

University of Michigan
Ann Arbor, Michigan 48109

Wayne State University-Detroit Receiving Hospital
Detroit, Michigan 48201

Henry Ford Health System
Detroit, Michigan 48202

Wayne State University-Sinai Grace Hospital
Detroit, Michigan 48235

Hennepin County Medical Center
Minneapolis, Minnesota 55415

University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota 55455

HealthPartners Institute
Saint Paul, Minnesota 55101

University of Missouri
Columbia, Missouri 65211

Cooper University Hospital
Camden, New Jersey 08103

Capital Health System, Inc.
Trenton, New Jersey 98638

University of New Mexico Hospital
Albuquerque, New Mexico 87106

Erie County Medical Center-Affliate of SUNYat Buffalo
Buffalo, New York 14215

Staten Island University Hospital-Northwell Health
Staten Island, New York 10305

Carolinas Medical Center
Charlotte, North Carolina 28208

East Carolina University
Greenville, North Carolina 27834

University of Cincinnati Medical Center (UCMC)
Cincinnati, Ohio 45219

The MetroHealth System
Cleveland, Ohio 44109

The Ohio State University
Columbus, Ohio 43210

Wright State University & Premier Health Clinical Trials Research Alliance
Dayton, Ohio 45409

St Elizabeth Youngstown Hospital
Youngstown, Ohio 44501

Oregon Health and Science University
Portland, Oregon 97239

St. Luke's University Health Network
Bethlehem, Pennsylvania 18015

The Pennsylvania State University and The Milton S. Hershey Medical Center
Hershey, Pennsylvania 17033

The Trauma Center at PENN
Philadelphia, Pennsylvania 19104

Thomas Jefferson University
Philadelphia, Pennsylvania 19107

University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania 15213

UT Southwestern Medical Center
Dallas, Texas 75390

John Peter Smith Health Network
Fort Worth, Texas 76104

Houston Methodist Hospital
Houston, Texas 77030

University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229

Harborview Medical Center
Seattle, Washington 98104

Medical College of Wisconsin-Froedtert Hospital
Milwaukee, Wisconsin 53226

More Details

NCT ID
NCT02469857
Status
Recruiting
Sponsor
Atox Bio Ltd

Study Contact

Wayne M Dankner, MD
919-219-6377
wayned@atoxbio.com

Detailed Description

The primary hypothesis of this study is that in addition to standard of care treatment (which includes surgical intervention, antimicrobial therapy and critical care support for organ dysfunction or failure), AB103 will demonstrate a clinically significant treatment benefit over placebo.

This hypothesis will be addressed by measuring the effect of AB103 on a composite of clinical parameters associated with the disease course of patients with NSTI, using a responder analysis. A responding patient must meet all 5 parameters of the composite clinical success end point, while a non-responding patient can fail by not meeting any one of the parameters. These analyses are designed to demonstrate that in addition to being safe, one dose of 0.5 mg/kg of AB103 will:

Improve systemic signs of the infection by improving organ function of patients compared to placebo as measured by:

- Survival at Day 28

- Modified SOFA (mSOFA) score on Day 14 and change from baseline to Day 14 ≥ 3. A Day 14 mSOFA score of ≤1 and a change from baseline (pre-treatment) to Day 14 ≥3 will be required for a patient to achieve the primary composite clinical success endpoint (NICCE)

Improve the local signs of the infection, as measured by:

- Reduced number of debridements, counted to Day 14. No more than 3 debridements to Day 14 will be required for a patient to achieve composite clinical success

- No amputation after the first debridement (amputation on the first debridement is not considered a failure). A patient will be required to have had no amputations done after the first surgical procedure in order to achieve composite clinical success.

290 patients will be recruited into the study and randomized to receive either 0.5 mg/kg AB103 or placebo in a 1:1 ratio. Randomization will be stratified within center by the diagnosis of Fournier's Gangrene and mSOFA score category (3-4 vs >4) at screening. The study will be conducted with interim analyses for futility at 100 patients and safety monitored by an independent Data Monitoring Board at regular planned intervals.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.