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Necrotizing Soft Tissue InfectionsPhase 3ACCUTENCT02469857

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

A Phase 3 study testing AB103 0.5 mg/kg and NaCl 0.9% in people with Necrotizing Soft Tissue Infections and Necrotizing Fasciitis, run by Atox Bio Ltd at 71 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 (NSTI) receiving standard of care therapy. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
AB103 0.5 mg/kg and NaCl 0.9%
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
290 participants
Where
71 sitesin 2 countries
Study dates
1 Dec 2015to 18 Oct 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Surgical confirmation of NSTI by attending surgeon;
  • 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;
  • 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);
  • If a woman is of childbearing potential, she must consistently use an acceptable method of contraception from baseline through Day 28;
  • 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.
  • Signed and dated informed consent (ICF) as defined by the Institutional Review Board (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

Who cannot join

  • BMI>51;
  • Patient who has been operated at least once for the current NSTI infection and had a curative deep tissue debridement;
  • Patients with overt peripheral vascular disease in the involved area ;
  • Diabetic patients with peripheral vascular disease who present with below the ankle infection;
  • Removed deep vein thrombosis (DVT) in area of NSTI as an exclusion criteria
  • Patient with burn wounds;
Show all 27Show fewer
  • 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;
  • Chronic neurological impairment that leads to a neuro mSOFA component ≥2;
  • Recent cerebrovascular accident in the last 3 months;
  • Patients with cardiac arrest requiring cardiopulmonary resuscitation within the past 30 days;
  • Patient is not expected to survive throughout 28 days of study due to underlying medical condition, such as poorly controlled neoplasm;
  • Patient or patient's family are not committed to aggressive management of the patient's condition;
  • 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:
  • Congestive heart failure (CHF){ New York Heart Association (NYHA) class III-IV}
  • Severe chronic pulmonary obstructive disease (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;
  • Known HIV infection with CD4 (cluster of differentiation 4) count < 200 cells/mm3 or < 14% of all lymphocytes;
  • Patients with known chronic kidney disease (documented pre-illness creatinine value(s) ≥2.0) or patients receiving renal replacement therapy for chronic kidney disease;
  • 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;
  • Pregnant or lactating women;
  • Previous enrollment in a clinical trial involving investigational drug or a medical device within 30 days;
  • Previous enrollment in this protocol, ATB-202 or the Phase 2 trial of AB103, ATB-201.

Trial locations and contacts

71 sites in 2 countries.

71 sites in 2 countries

United States61 sites

  • Albany Medical Center

    Albany, New York, 12208

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University at Grady Memorial Hospital

    Atlanta, Georgia, 30303

  • Augusta University Health

    Augusta, Georgia, 30912

  • University of Maryland R Adams Cowley Shock Trauma Center

    Baltimore, Maryland, 21201

  • Our Lady of the Lake Regional Medical Center

    Baton Rouge, Louisiana, 70808

  • Baton Rouge General Hospital

    Baton Rouge, Louisiana, 70809

  • St. Luke's University Health Network

    Bethlehem, Pennsylvania, 18015

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Erie County Medical Center-Affliate of SUNYat Buffalo

    Buffalo, New York, 14215

  • Cooper University Hospital

    Camden, New Jersey, 08103

  • Carolinas Medical Center

    Charlotte, North Carolina, 28208

  • University of Cincinnati Medical Center (UCMC)

    Cincinnati, Ohio, 45219

  • The MetroHealth System

    Cleveland, Ohio, 44109

  • UCH-Memorial Health System

    Colorado Springs, Colorado, 80909

  • University of Missouri

    Columbia, Missouri, 65211

  • The Ohio State University

    Columbus, Ohio, 43210

  • Wright State University & Premier Health Clinical Trials Research Alliance

    Dayton, Ohio, 45409

  • University of Colorado Hospital

    Denver, Colorado, 80045

  • 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

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Texas Tech University Health Sciences Center at El Paso

    El Paso, Texas, 79905

  • John Peter Smith Health Network

    Fort Worth, Texas, 76104

  • UF Health Shands Hospital

    Gainesville, Florida, 32610

  • East Carolina University

    Greenville, North Carolina, 27834

  • The Pennsylvania State University and The Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Baylor College of Medicine-Ben Taub Hospital

    Houston, Texas, 77030

  • University of Iowa Hospital and Clinics

    Iowa City, Iowa, 52242

  • University of Kentucky

    Lexington, Kentucky, 40536

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center

    Los Angeles, California, 90502

  • Ryder Trauma Center/Jackson Memorial Hospital

    Miami, Florida, 33136

  • Medical College of Wisconsin-Froedtert Hospital

    Milwaukee, Wisconsin, 53226

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • University of Minnesota Medical Center-Fairview

    Minneapolis, Minnesota, 55455

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Yale New Haven Hospital

    New Haven, Connecticut, 06520

  • LSU Health Science Center

    New Orleans, Louisiana, 70112

  • The Trauma Center at PENN

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Maricopa Medical Center

    Phoenix, Arizona, 85008

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Maine Medical Center

    Portland, Maine, 04102

  • Legacy Emanuel Hospital

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • University of California, Davis Medical Center

    Sacramento, California, 95817

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • UCSD Medical Center

    San Diego, California, 92103

  • Harborview Medical Center

    Seattle, Washington, 98104

  • St Louis University

    St Louis, Missouri, 63103

  • Staten Island University Hospital-Northwell Health

    Staten Island, New York, 10305

  • Scott and White Medical Center

    Temple, Texas, 76502

  • Capital Health System, Inc.

    Trenton, New Jersey, 98638

  • Banner University Medical Center

    Tucson, Arizona, 24857

  • Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • St Elizabeth Youngstown Hospital

    Youngstown, Ohio, 44501

Other trials in United States

France10 sites

  • Hộpital Estaing-CHU de Clermont-Ferrand

    Clermont-Ferrand

  • Hộpital Henri Mondor

    Créteil

  • Hôpital Bicêtre

    Le Kremlin-Bicêtre

  • Robert Salengro Hopital-CHRU Lille

    Lille

  • CHU de Limoges

    Limoges

  • Hôpital Edouard Herriot

    Lyon

  • CHRU Nancy, Hôpital Central

    Nancy

  • CHU de Nimes

    Nîmes

  • Hôpital de la Source, CHR Orleans

    Orléans

  • CHRU Bretonneau

    Tours

Other trials in France

About this study

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)

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

Read the 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.
Being tested
AB103 0.5 mg/kg, NaCl 0.9%
Keywords
AB103, Necrotizing fasciitis
Medical subject headings
Fasciitis, Necrotizing, Fournier Gangrene

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AB103 0.5 mg/kgDrug

    Also called reltecimod

  • NaCl 0.9%Other

    Also called Normal saline

Study groups in NCT02469857
Study groupRoleWhat they receive
AB103 0.5 mg/kgExperimentalAB103 0.5 mg/kg, IV, single dose
Receives: Drug: AB103 0.5 mg/kg
NaCl 0.9%Placebo comparatorNaCl 0.9%, IV, single dose
Receives: Other: NaCl 0.9%

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients Achieving Necrotizing Infections Clinical Composite Endpoint (NICCE)

    NICCE was made up of the following 5 components, all of which had to be met to successfully achieve the primary outcome measure (i.e., a "responder"): (i) Alive at Day 28, (ii) ≤ 3 debridements through Day 14, (iii) No amputation performed after the first debridement, (iv) Day 14 modified Sequential Organ Failure Assessment (mSOFA) score ≤ 1, and (v) Reduction of ≥ 3 mSOFA score points between Baseline and Day 14. This analysis compared responders in the reltecimod group versus responders in the placebo group.

    Modified Sequential Organ Failure Assessment (mSOFA) total scores range from 0 to 20, with higher scores reflecting a worse clinical status or outcome. An mSOFA total score of 0 or 1 reflects resolution of organ dysfunction/failure.

    Measured: 28 days

Secondary outcomes (9)

  1. Number of Patients With One or More Adverse Events (AEs)

    Number of Patients With One or More Adverse Events (AEs). Serious Adverse Events (SAEs) are included in this outcome measure since SAEs are a subset of AEs.

    Measured: 28 days

  2. Number of Patients With One or More Serious Adverse Events (SAEs)

    Number of Patients with One or More Serious Adverse Events (SAEs) During the Study

    Measured: 28 days

  3. Number of Patients With One or More Secondary Infections

    Number of Patients with One or More Secondary Infections During the Study

    Measured: 28 days

  4. Number of Patients Achieving Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Score of 0 or 1

    Modified Sequential Organ Failure Assessment (mSOFA) total scores range from 0 to 20, with higher scores reflecting a worse clinical status or outcome. An mSOFA total score of 0 or 1 reflects resolution of organ dysfunction/failure.

    Measured: 14 days

  5. Intensive Care Unit (ICU)-Free Days

    ICU-free days refers to the number of days a patient did not spend time in the ICU through Day 28.

    Measured: 28 days

  6. Ventilator-free Days

    Ventilator-free days refers to the number of days a patient was not on a ventilator through Day 28.

    Measured: 28 days

  7. Vasopressor-free Days

    Vasopressor-free days refers to the number of days a patient did not receive a vasopressor through Day 28.

    Measured: 28 days

  8. Hospital Days

    Hospital days refers to the number of days a patient spent time in the hospital.

    Measured: 90 days or until end of follow up

  9. Number of Patients With a More Favorable or Less Favorable Hospital Discharge Location

    Number of patients with more favorable discharge location (home or rehabilitation facility) or less favorable discharge location (skilled nursing facility, another acute care facility, death, other)

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2015 (estimated)
  2. Study start1 Dec 2015
  3. Primary completion18 Aug 2019
  4. Study completion18 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
290 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02469857
Sponsor's protocol ID
ATB-202
Acronym
ACCUTE
Status last verified
Oct 2021
First submitted
6 Jun 2015
Last updated
5 Oct 2021
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Bulger EM, May AK, Robinson BRH, Evans DC, Henry S, Green JM, Toschlog E, Sperry JL, Fagenholz P, Martin ND, Dankner WM, Maislin G, Wilfret D, Bernard AC; ACCUTE Study Investigators. A Novel Immune Modulator for Patients With Necrotizing Soft Tissue Infections (NSTI): Results of a Multicenter, Phase 3 Randomized Controlled Trial of Reltecimod (AB 103). Ann Surg. 2020 Sep 1;272(3):469-478. doi: 10.1097/SLA.0000000000004102.

    PubMed 32657946

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing AB103 0.5 mg/kg and NaCl 0.9% in people with Necrotizing Soft Tissue Infections and Necrotizing Fasciitis, run by Atox Bio Ltd at 71 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 71 sites in United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Achieving Necrotizing Infections Clinical Composite Endpoint (NICCE) (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02469857, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2021.

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