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Phase III Efficacy and Safety Study of AB103 in the Treatment of Patients With Necrotizing Soft Tissue Infections (ACCUTE)

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ClinicalTrials.gov Identifier: NCT02469857
Recruitment Status : Recruiting
First Posted : June 12, 2015
Last Update Posted : May 2, 2019
Sponsor:
Collaborator:
Biomedical Advanced Research and Development Authority
Information provided by (Responsible Party):
Atox Bio Ltd

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Necrotizing Soft Tissue Infections Necrotizing Fasciitis Fournier's Gangrene Drug: AB103 0.5 mg/kg Other: NaCl 0.9% Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 290 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Study of AB103 as Compared to Placebo in Patients With Necrotizing Soft Tissue Infections. ACCUTE (AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections)
Study Start Date : September 2015
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AB103 0.5 mg/kg
AB103 0.5 mg/kg, IV, single dose
Drug: AB103 0.5 mg/kg
Other Name: p2TA

Placebo Comparator: NaCl 0.9%
NaCl 0.9%, IV, single dose
Other: NaCl 0.9%
Other Name: Normal saline




Primary Outcome Measures :
  1. NICCE: Clinical composite success end point [ Time Frame: 28 days ]
    Success is defined as meeting all 5 components of the composite score: Alive until Day 28, (ii) Day 14 debridements ≤3 (iii) No amputation done after the first debridement (iv) Day 14 mSOFA score ≤1 (v) Reduction of ≥3 score points between Baseline and Day 14 mSOFA score

  2. Modified clinical composite endpoint: [ Time Frame: 28 days ]
    Success is defined as meeting all 3 components of the composite score: Alive until Day 28, (ii) Day 14 debridements ≤3 (iii) No amputation done after the first debridement


Secondary Outcome Measures :
  1. Safety measures Adverse Events [ Time Frame: 28 days ]
    Measures throughout Day 28: Adverse Events (includes Serious Adverse Events (SAEs).

  2. Safety measures Clinical safety laboratory [ Time Frame: 28 days ]
    Measures throughout Day 14: Clinical safety laboratory

  3. Safety measures Secondary infections [ Time Frame: 28 days ]
    Measures throughout Day 28: Secondary infections

  4. Recovery from acute kidney injury [ Time Frame: 28 days ]
  5. Time to resolution of mSOFA score to ≤ 1 [ Time Frame: 14 days ]
  6. Critical care and hospital stay parameters ICU days [ Time Frame: 28 days ]
    ICU days

  7. Critical care and hospital stay parameters Ventilator days [ Time Frame: 28 days ]
    Ventilator days

  8. Critical care and hospital stay parameters Hospital length of stay [ Time Frame: 28 days ]
    Hospital length of stay



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

    • CHF {NYHA class III-IV}
    • Severe COPD
    • Liver dysfunction {Childs-Pugh class C}
    • Immunosuppression (see Appendix F, Section 15.6 for list of excluded immunosuppressive medications)
    • Neutropenia < 1,000 cells/mm3not due to the underlying infection
    • Idiopathic Thrombocytopenia Purpura
    • Receiving or about to receive chemotherapy or biologic anti-cancer treatment although hormonal manipulation therapies for breast and prostate malignancies are permitted
    • Hematological and lymphatic malignancies in the last 5 years;
  14. Known HIV infection with CD4 count < 200 cells/mm3 or < 14% of all lymphocytes;
  15. Patients with known chronic kidney disease (documented pre-illness creatinine value(s) ≥2.0) or patients receiving renal replacement therapy for chronic kidney disease;
  16. 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;
  17. Pregnant or lactating women;
  18. Previous enrollment in a clinical trial involving investigational drug or a medical device within 30 days;
  19. Previous enrollment in this protocol, ATB-202 or the Phase 2 trial of AB103, ATB-201.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02469857


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

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Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Principal Investigator: Ross M Vander Noot, MD         
United States, Arizona
Maricopa Medical Center Recruiting
Phoenix, Arizona, United States, 85008
Principal Investigator: Kevin Foster, MD         
Banner University Medical Center Recruiting
Tucson, Arizona, United States, 24857
Principal Investigator: Gary Vercruysse, MD         
United States, Arkansas
University of Arkansas for Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72205
Principal Investigator: Kevin Sexton, MD         
United States, California
Loma Linda University Medical Center Recruiting
Loma Linda, California, United States, 92354
Principal Investigator: Richard Catalano, MD         
Keck Hospital of USC Withdrawn
Los Angeles, California, United States, 90033
University of Southern California-LAC+USC Medical Center Withdrawn
Los Angeles, California, United States, 90033
Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center Recruiting
Los Angeles, California, United States, 90502
Principal Investigator: Dennis Kim, MD         
University of California, Irvine Medical Center Withdrawn
Orange, California, United States, 92868
University of California, Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Principal Investigator: Christine S Cocanour, MD         
UCSD Medical Center Recruiting
San Diego, California, United States, 92103
Principal Investigator: Leslie Kobayashi, MD         
United States, Colorado
UCH-Memorial Health System Recruiting
Colorado Springs, Colorado, United States, 80909
Principal Investigator: Thomas Schroeppel, MD         
University of Colorado Hospital Recruiting
Denver, Colorado, United States, 80045
Principal Investigator: Robert McIntyre, MD         
Denver Health Medical Center Withdrawn
Denver, Colorado, United States, 80204
United States, Connecticut
Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06520
Principal Investigator: Adrian Maung, MD         
United States, Delaware
Christiana Care Health System Withdrawn
Newark, Delaware, United States, 19718
United States, District of Columbia
Washington Hospital Center Recruiting
Washington, District of Columbia, United States, 20010
Principal Investigator: Jack A Sava, MD         
United States, Florida
UF Health Shands Hospital Recruiting
Gainesville, Florida, United States, 32610
Principal Investigator: Scott Brakenridge, MD         
Ryder Trauma Center/Jackson Memorial Hospital Completed
Miami, Florida, United States, 33136
United States, Georgia
Emory University at Grady Memorial Hospital Recruiting
Atlanta, Georgia, United States, 30303
Principal Investigator: Rondi Gelbard, MD         
Joseph M. Still Burn Center at Doctors Hospital Withdrawn
Augusta, Georgia, United States, 30909
Augusta University Health Recruiting
Augusta, Georgia, United States, 30912
Principal Investigator: Lester Young, MD         
United States, Illinois
Loyola University Medical Center Withdrawn
Maywood, Illinois, United States, 60153
United States, Indiana
Indiana University Health Methodist Hospital Withdrawn
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Hospital and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Principal Investigator: Kent Choi, MD         
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Principal Investigator: Andrew Bernard, MD         
University of Louisville Withdrawn
Louisville, Kentucky, United States, 40202
United States, Louisiana
Our Lady of the Lake Regional Medical Center Recruiting
Baton Rouge, Louisiana, United States, 70808
Principal Investigator: Hollis O'Neal, MD         
Baton Rouge General Hospital Recruiting
Baton Rouge, Louisiana, United States, 70809
Principal Investigator: Hollis O'Neal, MD         
LSU Health Science Center Recruiting
New Orleans, Louisiana, United States, 70112
Principal Investigator: Patrick Greiffenstein, MD         
United States, Maine
Maine Medical Center Recruiting
Portland, Maine, United States, 04102
Principal Investigator: Joseph Rappold, MD         
United States, Maryland
University of Maryland R Adams Cowley Shock Trauma Center Recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Sharon Henry, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Peter Fagenholz, MD         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Reza Askari, MD         
Boston Medical Center Withdrawn
Boston, Massachusetts, United States, 02118
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Principal Investigator: Pauline Park, MD         
Wayne State University-Detroit Receiving Hospital Recruiting
Detroit, Michigan, United States, 48201
Principal Investigator: Lawrence Diebel, MD         
Principal Investigator: Robert Sherwin, MD         
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Principal Investigator: Jeffrey Johnson, MD         
Wayne State University-Sinai Grace Hospital Recruiting
Detroit, Michigan, United States, 48235
Principal Investigator: Robert Sherwin, MD         
Principal Investigator: Lawrence Diebel, MD         
United States, Minnesota
Fairview Southdale Hospital Recruiting
Edina, Minnesota, United States, 55435
Principal Investigator: Julie Ottosen, MD         
Hennepin County Medical Center Recruiting
Minneapolis, Minnesota, United States, 55415
Principal Investigator: Frederick Endorf, MD         
University of Minnesota Medical Center-Fairview Recruiting
Minneapolis, Minnesota, United States, 55455
Principal Investigator: Julie Ottosen, MD         
HealthPartners Institute Withdrawn
Saint Paul, Minnesota, United States, 55101
United States, Missouri
University of Missouri Recruiting
Columbia, Missouri, United States, 65211
Principal Investigator: Jacob Quick, MD         
St Louis University Recruiting
Saint Louis, Missouri, United States, 63103
Principal Investigator: Carl A Freeman, MD         
United States, New Jersey
Cooper University Hospital Recruiting
Camden, New Jersey, United States, 08103
Principal Investigator: Ju Lin Wang, MD         
Capital Health System, Inc. Recruiting
Trenton, New Jersey, United States, 98638
Principal Investigator: Michael Kalina, MD         
United States, New Mexico
University of New Mexico Hospital Withdrawn
Albuquerque, New Mexico, United States, 87106
United States, New York
Albany Medical Center Recruiting
Albany, New York, United States, 12208
Principal Investigator: Marcel W Tafen, MD         
Montefiore Medical Center-Weiler Division Withdrawn
Bronx, New York, United States, 10461
Montefiore Medical Center-Moses Division Withdrawn
Bronx, New York, United States, 10467
Erie County Medical Center-Affliate of SUNYat Buffalo Recruiting
Buffalo, New York, United States, 14215
Principal Investigator: William Flynn, MD         
Staten Island University Hospital-Northwell Health Completed
Staten Island, New York, United States, 10305
United States, North Carolina
Carolinas Medical Center Recruiting
Charlotte, North Carolina, United States, 28208
Principal Investigator: John Green, MD         
East Carolina University Recruiting
Greenville, North Carolina, United States, 27834
Principal Investigator: Eric Toschlog, MD         
United States, Ohio
University of Cincinnati Medical Center (UCMC) Recruiting
Cincinnati, Ohio, United States, 45219
Principal Investigator: Timothy Pritts, MD         
The MetroHealth System Recruiting
Cleveland, Ohio, United States, 44109
Principal Investigator: Jeffrey A Claridge, MD         
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Principal Investigator: David Evans, MD         
Wright State University & Premier Health Clinical Trials Research Alliance Completed
Dayton, Ohio, United States, 45409
University of Toledo Medical Center Withdrawn
Toledo, Ohio, United States, 43614
St Elizabeth Youngstown Hospital Recruiting
Youngstown, Ohio, United States, 44501
Principal Investigator: Gregory Huang, MD         
United States, Oklahoma
Oklahoma University Health Science Center Withdrawn
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Legacy Emanuel Hospital Completed
Portland, Oregon, United States, 97227
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Principal Investigator: Martin Schreiber, MD         
United States, Pennsylvania
St. Luke's University Health Network Recruiting
Bethlehem, Pennsylvania, United States, 18015
Principal Investigator: John Lukaszczyk, MD         
The Pennsylvania State University and The Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
Principal Investigator: Melissa Boltz, MD         
The Trauma Center at PENN Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Niels Martin, MD         
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Principal Investigator: Joshua Marks, MD         
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Principal Investigator: Jason Sperry, MD         
United States, Tennessee
Vanderbilt University Medical Center Completed
Nashville, Tennessee, United States, 37232
United States, Texas
UT Southwestern Medical Center Withdrawn
Dallas, Texas, United States, 75390
Texas Tech University Health Sciences Center at El Paso Terminated
El Paso, Texas, United States, 79905
John Peter Smith Health Network Recruiting
Fort Worth, Texas, United States, 76104
Principal Investigator: Rajesh Ghandi, MD         
Baylor College of Medicine-Ben Taub Hospital Terminated
Houston, Texas, United States, 77030
Houston Methodist Hospital Withdrawn
Houston, Texas, United States, 77030
University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229
Principal Investigator: Christopher Crane, MD         
Scott and White Medical Center Recruiting
Temple, Texas, United States, 76502
Principal Investigator: Justin Regner, MD         
United States, Virginia
Virginia Commonwealth University Withdrawn
Richmond, Virginia, United States, 23298
United States, Washington
Harborview Medical Center Recruiting
Seattle, Washington, United States, 98104
Principal Investigator: Eileen M Bulger, MD         
United States, Wisconsin
Medical College of Wisconsin-Froedtert Hospital Recruiting
Milwaukee, Wisconsin, United States, 53226
Principal Investigator: Todd Neideen, MD         
France
Hộpital Estaing-CHU de Clermont-Ferrand Recruiting
Clermont-Ferrand, France
Principal Investigator: Jean-Michel Constantin, Pr         
Hộpital Henri Mondor Recruiting
Créteil, France
Principal Investigator: Nicolas De Prost, Dr         
Hôpital Bicêtre Recruiting
Le Kremlin-Bicêtre, France
Principal Investigator: Christian Richard, Pr         
Robert Salengro Hopital-CHRU Lille Recruiting
Lille, France
Principal Investigator: Daniel Mathieu, Pr         
CHU de Limoges Recruiting
Limoges, France
Principal Investigator: Thomas Lafon, Dr         
Hôpital Edouard Herriot Recruiting
Lyon, France
Principal Investigator: Baptiste Hengy, Dr         
CHRU Nancy, Hôpital Central Recruiting
Nancy, France
Principal Investigator: Sebastien Gibot, Pr         
CHU de Nimes Recruiting
Nîmes, France
Principal Investigator: Jean-Yves LeFrant, Pr         
Hôpital de la Source, CHR Orleans Recruiting
Orléans, France
Principal Investigator: Thierry Boulain, Dr         
CHRU Bretonneau Recruiting
Tours, France
Principal Investigator: Emmanuelle Mercier, Dr         
Sponsors and Collaborators
Atox Bio Ltd
Biomedical Advanced Research and Development Authority
Investigators
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Study Director: Wayne M Dankner, MD Atox Bio Ltd
Principal Investigator: Eileen M Bulger, MD Harborview Injury Prevention and Research Center

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Responsible Party: Atox Bio Ltd
ClinicalTrials.gov Identifier: NCT02469857     History of Changes
Other Study ID Numbers: ATB-202
First Posted: June 12, 2015    Key Record Dates
Last Update Posted: May 2, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Atox Bio Ltd:
AB103
Necrotizing fasciitis

Additional relevant MeSH terms:
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Fasciitis
Fasciitis, Necrotizing
Infection
Communicable Diseases
Soft Tissue Infections
Gangrene
Fournier Gangrene
Musculoskeletal Diseases
Necrosis
Pathologic Processes
Skin Diseases, Bacterial
Bacterial Infections
Genital Diseases, Male