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| Name | Class |
|---|---|
| Biomedical Advanced Research and Development Authority | FED |
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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.
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:
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AB103 0.5 mg/kg | Experimental | AB103 0.5 mg/kg, IV, single dose |
|
| NaCl 0.9% | Placebo Comparator | NaCl 0.9%, IV, single dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AB103 0.5 mg/kg | Drug |
|
| |
| NaCl 0.9% |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 28 days |
| Number of Patients With One or More Serious Adverse Events (SAEs) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Deaths From Day 0 Through Day 90 | The number of deaths occurring from Study Day 0 through Study Day 90 | 90 days |
| Number of Deaths After Day 14 Through Day 90 | Number of deaths after Study Day 14 through Study Day 90 |
Inclusion Criteria:
Exclusion Criteria:
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;
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Wayne M Dankner, MD | Atox Bio Ltd | Study Director |
| Eileen M Bulger, MD | Harborview Injury Prevention and Research Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States | ||
| Maricopa Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32657946 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Reltecimod (AB103) 0.5 mg/kg | Reltecimod 0.5 mg/kg, single IV infusion over approximately 10 minutes |
| FG001 | Placebo | NaCl 0.9%, single IV infusion over approximately 10 minutes |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 23, 2018 | Aug 27, 2021 |
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| Other |
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|
Number of Patients with One or More Serious Adverse Events (SAEs) During the Study |
| 28 days |
| Number of Patients With One or More Secondary Infections | Number of Patients with One or More Secondary Infections During the Study | 28 days |
| 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. | 14 days |
| 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. | 28 days |
| Ventilator-free Days | Ventilator-free days refers to the number of days a patient was not on a ventilator through Day 28. | 28 days |
| Vasopressor-free Days | Vasopressor-free days refers to the number of days a patient did not receive a vasopressor through Day 28. | 28 days |
| Hospital Days | Hospital days refers to the number of days a patient spent time in the hospital. | 90 days or until end of follow up |
| 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) | 90 days |
| 76 days (after Day 14 through Day 90) |
| Number of Deaths From Day 0 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5 | Number and percentage of patients with a Screening mSOFA score of at least 5 who were alive on Study Day 0 and subsequently died through Study Day 90. | 90 days |
| Number of Deaths After Day 14 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5 | Number and percentage of patients with a Screening mSOFA score of at least 5 who were alive on Study Day 14 and subsequently died through Study Day 90. | 76 days (after Day 14 through Day 90) |
| Number of Deaths From Day 0 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock) | Number and percentage of patients with baseline cardiovascular failure (shock) who died through Study Day 90. | 90 days |
| Number of Deaths After Day 14 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock) | Number and percentage of patients with baseline cardiovascular failure (shock) who were alive on Study Day 14 and subsequently died through Study Day 90. | 76 days (after Day 14 through Day 90) |
| Number of Patients With a Screening Modified Sequential Organ Failure Assessment (mSOFA) Score of at Least 5 Who Achieved 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) 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. 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. | 28 days |
| Number of Patients With a Screening mSOFA Score of at Least 5 Who Achieved 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. | 14 days |
| Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved 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) 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. | 28 days |
| Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved 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. | 14 days |
| Phoenix |
| Arizona |
| 85008 |
| United States |
| Banner University Medical Center | Tucson | Arizona | 24857 | United States |
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States |
| Loma Linda University Medical Center | Loma Linda | California | 92354 | United States |
| Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center | Los Angeles | California | 90502 | United States |
| University of California, Davis Medical Center | Sacramento | California | 95817 | United States |
| UCSD Medical Center | San Diego | California | 92103 | United States |
| UCH-Memorial Health System | Colorado Springs | Colorado | 80909 | United States |
| University of Colorado Hospital | Denver | Colorado | 80045 | United States |
| Yale New Haven Hospital | New Haven | Connecticut | 06520 | United States |
| Washington Hospital Center | Washington D.C. | District of Columbia | 20010 | United States |
| UF Health Shands Hospital | Gainesville | Florida | 32610 | United States |
| Ryder Trauma Center/Jackson Memorial Hospital | Miami | Florida | 33136 | United States |
| Emory University at Grady Memorial Hospital | Atlanta | Georgia | 30303 | United States |
| Augusta University Health | Augusta | Georgia | 30912 | United States |
| University of Iowa Hospital and Clinics | Iowa City | Iowa | 52242 | United States |
| University of Kentucky | Lexington | Kentucky | 40536 | United States |
| Our Lady of the Lake Regional Medical Center | Baton Rouge | Louisiana | 70808 | United States |
| Baton Rouge General Hospital | Baton Rouge | Louisiana | 70809 | United States |
| LSU Health Science Center | New Orleans | Louisiana | 70112 | United States |
| Maine Medical Center | Portland | Maine | 04102 | United States |
| University of Maryland R Adams Cowley Shock Trauma Center | Baltimore | Maryland | 21201 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Wayne State University-Detroit Receiving Hospital | Detroit | Michigan | 48201 | United States |
| Henry Ford Health System | Detroit | Michigan | 48202 | United States |
| Wayne State University-Sinai Grace Hospital | Detroit | Michigan | 48235 | United States |
| Fairview Southdale Hospital | Edina | Minnesota | 55435 | United States |
| Hennepin County Medical Center | Minneapolis | Minnesota | 55415 | United States |
| University of Minnesota Medical Center-Fairview | Minneapolis | Minnesota | 55455 | United States |
| University of Missouri | Columbia | Missouri | 65211 | United States |
| St Louis University | St Louis | Missouri | 63103 | United States |
| Cooper University Hospital | Camden | New Jersey | 08103 | United States |
| Capital Health System, Inc. | Trenton | New Jersey | 98638 | United States |
| Albany Medical Center | Albany | New York | 12208 | United States |
| Erie County Medical Center-Affliate of SUNYat Buffalo | Buffalo | New York | 14215 | United States |
| Staten Island University Hospital-Northwell Health | Staten Island | New York | 10305 | United States |
| Carolinas Medical Center | Charlotte | North Carolina | 28208 | United States |
| East Carolina University | Greenville | North Carolina | 27834 | United States |
| University of Cincinnati Medical Center (UCMC) | Cincinnati | Ohio | 45219 | United States |
| The MetroHealth System | Cleveland | Ohio | 44109 | United States |
| The Ohio State University | Columbus | Ohio | 43210 | United States |
| Wright State University & Premier Health Clinical Trials Research Alliance | Dayton | Ohio | 45409 | United States |
| St Elizabeth Youngstown Hospital | Youngstown | Ohio | 44501 | United States |
| Legacy Emanuel Hospital | Portland | Oregon | 97227 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| St. Luke's University Health Network | Bethlehem | Pennsylvania | 18015 | United States |
| The Pennsylvania State University and The Milton S. Hershey Medical Center | Hershey | Pennsylvania | 17033 | United States |
| The Trauma Center at PENN | Philadelphia | Pennsylvania | 19104 | United States |
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15213 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Texas Tech University Health Sciences Center at El Paso | El Paso | Texas | 79905 | United States |
| John Peter Smith Health Network | Fort Worth | Texas | 76104 | United States |
| Baylor College of Medicine-Ben Taub Hospital | Houston | Texas | 77030 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| Scott and White Medical Center | Temple | Texas | 76502 | United States |
| Harborview Medical Center | Seattle | Washington | 98104 | United States |
| Medical College of Wisconsin-Froedtert Hospital | Milwaukee | Wisconsin | 53226 | United States |
| Há»™pital Estaing-CHU de Clermont-Ferrand | Clermont-Ferrand | France |
| Hộpital Henri Mondor | Créteil | France |
| Hôpital Bicêtre | Le Kremlin-Bicêtre | France |
| Robert Salengro Hopital-CHRU Lille | Lille | France |
| CHU de Limoges | Limoges | France |
| Hôpital Edouard Herriot | Lyon | France |
| CHRU Nancy, Hôpital Central | Nancy | France |
| CHU de Nimes | Nîmes | France |
| Hôpital de la Source, CHR Orleans | Orléans | France |
| CHRU Bretonneau | Tours | France |
|
| COMPLETED | As Treated (Safety) Analysis Set |
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| NOT COMPLETED |
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|
This analysis population (As Treated/Safety Analysis Set) included all randomized patients who were exposed to study drug (reltecimod or placebo), with patients analyzed according to the treatment actually received.
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| ID | Title | Description |
|---|---|---|
| BG000 | Reltecimod (AB103) 0.5 mg/kg | Reltecimod 0.5 mg/kg, single IV infusion over approximately 10 minutes |
| BG001 | Placebo | NaCl 0.9%, single IV infusion over approximately 10 minutes |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Instead of collecting data in the categories "More than one race" and "Unknown or Not Reported," data were collected in the categories "Other" and "Missing." Counts of participants in these latter 2 categories were summed and included in the category of "Unknown or Not Reported" in this study record. | Count of Participants | Participants |
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| Region of Enrollment | This measure represents the two countries from which patients were enrolled into this study and received study drug (i.e., United States and France). | Number | participants |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
| |||||||||||||||
| Necrotizing Soft Tissue Infection (NSTI) Diagnosis | Count of Participants | Participants |
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| Comorbidities | Count of Participants | Participants |
| ||||||||||||||||
| Modified Sequential Organ Failure Assessment (mSOFA) Score | 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. | Mean | Standard Deviation | score on a scale |
| ||||||||||||||
| Acute Physiology And Chronic Health Evaluation II (APACHE II) Score | The Acute Physiology and Chronic Health Evaluation (APACHE) Score is a severity of illness classification system. It is determined within 24 hours of admission of a patient to an intensive care unit (ICU): an integer score from 0 to 71 is computed based on several measurements (physiologic variables, age, chronic health status). Higher scores correspond to more severe disease and a greater risk of death. | Mean | Standard Deviation | score on a scale |
| ||||||||||||||
| Sepsis Presentation | Sepsis presentation is based on mSOFA cardiovascular and respiratory sub-score components equal to 3 or 4. | Count of Participants | Participants |
| |||||||||||||||
| Acute Kidney Injury (AKI) Presentation | Stages of acute kidney injury (AKI) refer to the Kidney Disease: Improving Global Outcomes (KDIGO) stages of AKI. There are 3 KDIGO stages of AKI that are based on serum creatinine or urine output. Stage 1 represents the least severity of AKI, while Stage 3 represents the greatest severity of AKI. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The primary analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. A secondary analysis of the primary outcome measure utilized the United States-modified intent-to-treat (US-mITT) analysis population which consisted only of mITT patients enrolled in the United States. | Posted | Count of Participants | Participants | 28 days |
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| Secondary | 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. | As Treated/Safety Analysis Population: all randomized patients who were exposed to study drug (active or placebo) and categorized according to the treatment actually received. | Posted | Count of Participants | Participants | 28 days |
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| Secondary | 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 | As Treated/Safety Analysis Population: all randomized patients who were exposed to study drug (active or placebo) and categorized according to the treatment actually received. | Posted | Count of Participants | Participants | 28 days |
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| Secondary | Number of Patients With One or More Secondary Infections | Number of Patients with One or More Secondary Infections During the Study | As Treated/Safety Analysis Population: all randomized patients who were exposed to study drug (active or placebo) and categorized according to the treatment actually received. | Posted | Count of Participants | Participants | 28 days |
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| Secondary | 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. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. | Posted | Count of Participants | Participants | 14 days |
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| Secondary | 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. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. | Posted | Median | Full Range | days | 28 days |
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| Secondary | Ventilator-free Days | Ventilator-free days refers to the number of days a patient was not on a ventilator through Day 28. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. | Posted | Median | Full Range | days | 28 days |
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| Secondary | Vasopressor-free Days | Vasopressor-free days refers to the number of days a patient did not receive a vasopressor through Day 28. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. | Posted | Median | Full Range | days | 28 days |
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| Secondary | Hospital Days | Hospital days refers to the number of days a patient spent time in the hospital. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. | Posted | Median | Full Range | days | 90 days or until end of follow up |
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| Secondary | 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) | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. | Posted | Count of Participants | Participants | 90 days |
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| Other Pre-specified | Number of Deaths From Day 0 Through Day 90 | The number of deaths occurring from Study Day 0 through Study Day 90 | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. | Posted | Count of Participants | Participants | 90 days |
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| Other Pre-specified | Number of Deaths After Day 14 Through Day 90 | Number of deaths after Study Day 14 through Study Day 90 | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. Data from patients in the US-mITT population alive on Day 14 (119 reltecimod patients and 124 placebo patients) were included in this analysis. | Posted | Count of Participants | Participants | 76 days (after Day 14 through Day 90) |
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| Other Pre-specified | Number of Deaths From Day 0 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5 | Number and percentage of patients with a Screening mSOFA score of at least 5 who were alive on Study Day 0 and subsequently died through Study Day 90. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. Data from patients in the US-mITT population with a Screening mSOFA score of at least 5 were included in this analysis. | Posted | Count of Participants | Participants | 90 days |
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| Other Pre-specified | Number of Deaths After Day 14 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5 | Number and percentage of patients with a Screening mSOFA score of at least 5 who were alive on Study Day 14 and subsequently died through Study Day 90. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. Data from patients in the US-mITT population with a Screening mSOFA score of at least 5 who were alive on Day 14 (64 reltecimod patients and 69 placebo patients) were included in this analysis. | Posted | Count of Participants | Participants | 76 days (after Day 14 through Day 90) |
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| Other Pre-specified | Number of Deaths From Day 0 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock) | Number and percentage of patients with baseline cardiovascular failure (shock) who died through Study Day 90. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. Data from patients in the US-mITT population with baseline cardiovascular failure (i.e., shock; 75 reltecimod patients and 56 placebo patients) were included in this analysis. | Posted | Count of Participants | Participants | 90 days |
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| Other Pre-specified | Number of Deaths After Day 14 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock) | Number and percentage of patients with baseline cardiovascular failure (shock) who were alive on Study Day 14 and subsequently died through Study Day 90. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. Data from patients in the US-mITT population with baseline cardiovascular failure (i.e., shock; 63 reltecimod patients and 48 placebo patients) were included in this analysis. | Posted | Count of Participants | Participants | 76 days (after Day 14 through Day 90) |
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| Other Pre-specified | Number of Patients With a Screening Modified Sequential Organ Failure Assessment (mSOFA) Score of at Least 5 Who Achieved 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) 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. 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. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. Data from patients in the US-mITT population with a Screening mSOFA score of at least 5 (77 reltecimod patients and 79 placebo patients) were included in this analysis. | Posted | Count of Participants | Participants | 28 days |
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| Other Pre-specified | Number of Patients With a Screening mSOFA Score of at Least 5 Who Achieved 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. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. Data from patients in the US-mITT population with a Screening mSOFA score of at least 5 (77 reltecimod patients and 79 placebo patients) were included in this analysis. | Posted | Count of Participants | Participants | 14 days |
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| Other Pre-specified | Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved 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) 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. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. Data from patients in the US-mITT population with baseline cardiovascular failure (i.e., shock; 75 reltecimod patients and 56 placebo patients) were included in this analysis. | Posted | Count of Participants | Participants | 28 days |
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| Other Pre-specified | Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved 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. | The United States modified intent-to-treat (US-mITT) population included all randomized patients in the United States who were exposed to study drug and who had a definitive diagnosis of NSTI based on surgical verification. This population does not include 17 patients randomized in France. Data from patients in the US-mITT population with baseline cardiovascular failure (i.e., shock; 75 reltecimod patients and 56 placebo patients) were included in this analysis. | Posted | Count of Participants | Participants | 14 days |
|
|
Adverse event (AE) data were collected from study drug administration through the Day 28 visit. Data associated with deaths and study drug-related serious adverse events (SAEs) were collected from study drug administration though the Day 90 visit.
Safety data obtained during study visits associated with Study Days 1, 2, 3, 7, 10, 14, 21, and 28 were systematically assessed throughout the study. In addition, data from spontaneously reported AEs were included in safety assessments. Data associated with deaths and study drug-related serious adverse events (SAEs) were collected from study drug administration though the Day 90 visit.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Reltecimod (AB103) 0.5 mg/kg | Reltecimod (AB103) 0.5 mg/kg, single IV infusion over approximately 10 minutes | 24 | 143 | 44 | 143 | 24 | 143 |
| EG001 | Placebo | NaCl 0.9%, single IV infusion over approximately 10 minutes | 29 | 147 | 40 | 147 | 25 | 147 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Coronary artery perforation | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Pulmonary valve incompetence | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Pulseless electrical activity | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Ventricular fibrillation | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Abdominal compartment syndrome | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Intestinal infarction | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Intestinal perforation | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Lower gastrointestinal hemorrhage | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Rectal hemorrhage | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Small intestinal perforation | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Upper gastrointestinal hemorrhage | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Organ failure | General disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Liver disorder | Hepatobiliary disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Bacteremia | Infections and infestations | MedDRA version 21.0 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA version 21.0 | Systematic Assessment |
| |
| Funguria | Infections and infestations | MedDRA version 21.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA version 21.0 | Systematic Assessment |
| |
| Necrotizing fasciitis | Infections and infestations | MedDRA version 21.0 | Systematic Assessment |
| |
| Necrotizing soft tissue infection | Infections and infestations | MedDRA version 21.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 21.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA version 21.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA version 21.0 | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA version 21.0 | Systematic Assessment |
| |
| Hyperkalemia | Metabolism and nutrition disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Hypoglycemic coma | Nervous system disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Nervous system disorder | Nervous system disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Device malfunction | Product Issues | MedDRA version 21.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Acute lung injury | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Bronchopleural fistula | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Pulmonary edema | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Skin discoloration | Skin and subcutaneous tissue disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Skin necrosis | Skin and subcutaneous tissue disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Leg amputation | Surgical and medical procedures | MedDRA version 21.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Extremity necrosis | Vascular disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Malignant hypertension | Vascular disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Peripheral ischemia | Vascular disorders | MedDRA version 21.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 21.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Wayne M Dankner, MD, Chief Medical Officer | Atox Bio, Ltd. | 1-919-219-6377 | wayned@atoxbio.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 24, 2019 | Aug 27, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D019115 | Fasciitis, Necrotizing |
| D018934 | Fournier Gangrene |
| ID | Term |
|---|---|
| D005208 | Fasciitis |
| D009140 | Musculoskeletal Diseases |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000597133 | AB103 |
| D012965 | Sodium Chloride |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| France |
|
| Fournier's Gangrene |
|
| Gas Gangrene/Myonecrosis |
|
| Other NSTI |
|
| Cardiovascular Disease |
|
| Smoker |
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| Alcohol Abuse |
|
| Respiratory Organ Failure |
|
| Stage 2 or 3 AKI at Screening |
|
| US-mITT Population |
|
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| 0.025 |
| Superiority |
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