Fournier's Gangrene, Necrotizing Fasciitis, Necrotizing Soft Tissue Infections
Conditions
Keywords
AB103, Necrotizing fasciitis
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 (NSTI) receiving standard of care therapy.
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.
Interventions
DRUGAB103 0.5 mg/kg
OTHERNaCl 0.9%
Sponsors
Biomedical Advanced Research and Development Authority
Atox Bio Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Surgical confirmation of NSTI by attending surgeon; 2. mSOFA score ≥3 (in any one or combination of the 5 major components of SOFA score with one organ component having a score of at least 2: cardiovascular, respiratory, renal, coagulation, CNS), measured as close as possible to the first debridement; 3. IV drug administration within 6 hours from the clinical diagnosis and the decision at the study site, to have an urgent surgical exploration and debridement (drug should not be administered until surgical confirmation is established); 4. If a woman is of childbearing potential, she must consistently use an acceptable method of contraception from baseline through Day 28; 5. If a male patient's sexual partner is of childbearing potential, the male patient must acknowledge that they will consistently use an acceptable method of contraception (defined above) from baseline through Day 28. 6. Signed and dated 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
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 deep vein thrombosis (DVT) in area of NSTI as an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Achieving Necrotizing Infections Clinical Composite Endpoint (NICCE) | 28 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With One or More Adverse Events (AEs) | 28 days | 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. |
| Number of Patients With One or More Serious Adverse Events (SAEs) | 28 days | Number of Patients with One or More Serious Adverse Events (SAEs) During the Study |
| Number of Patients With One or More Secondary Infections | 28 days | Number of Patients with One or More Secondary Infections During the Study |
| Number of Patients Achieving Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Score of 0 or 1 | 14 days | 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. |
| Intensive Care Unit (ICU)-Free Days | 28 days | ICU-free days refers to the number of days a patient did not spend time in the ICU through Day 28. |
| Ventilator-free Days | 28 days | Ventilator-free days refers to the number of days a patient was not on a ventilator through Day 28. |
| Vasopressor-free Days | 28 days | Vasopressor-free days refers to the number of days a patient did not receive a vasopressor through Day 28. |
| Hospital Days | 90 days or until end of follow up | Hospital days refers to the number of days a patient spent time in the hospital. |
| Number of Patients With a More Favorable or Less Favorable Hospital Discharge Location | 90 days | 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Deaths From Day 0 Through Day 90 | 90 days | The number of deaths occurring from Study Day 0 through Study Day 90 |
| Number of Deaths After Day 14 Through Day 90 | 76 days (after Day 14 through Day 90) | Number of deaths after Study Day 14 through Study Day 90 |
| Number of Deaths From Day 0 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5 | 90 days | 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. |
| Number of Deaths After Day 14 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5 | 76 days (after Day 14 through Day 90) | 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. |
| Number of Deaths From Day 0 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock) | 90 days | Number and percentage of patients with baseline cardiovascular failure (shock) who died through Study Day 90. |
| Number of Deaths After Day 14 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock) | 76 days (after Day 14 through Day 90) | Number and percentage of patients with baseline cardiovascular failure (shock) who were alive on Study Day 14 and subsequently died through Study Day 90. |
| Number of Patients With a Screening Modified Sequential Organ Failure Assessment (mSOFA) Score of at Least 5 Who Achieved NICCE | 28 days | 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. |
| 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 | 14 days | 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. |
| Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved NICCE | 28 days | 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. |
| Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Score of 0 or 1 | 14 days | 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. |
Countries
France, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Reltecimod (AB103) 0.5 mg/kg Reltecimod 0.5 mg/kg, single IV infusion over approximately 10 minutes | 143 |
| Placebo NaCl 0.9%, single IV infusion over approximately 10 minutes | 147 |
| Total | 290 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 24 | 29 |
| Overall Study | Discontinuation | 1 | 3 |
Baseline characteristics
| Characteristic | Total | Placebo | Reltecimod (AB103) 0.5 mg/kg |
|---|---|---|---|
| Acute Kidney Injury (AKI) Presentation Any AKI at Screening | 190 Participants | 103 Participants | 87 Participants |
| Acute Kidney Injury (AKI) Presentation Stage 2 or 3 AKI at Screening | 143 Participants | 81 Participants | 62 Participants |
| Acute Physiology And Chronic Health Evaluation II (APACHE II) Score | 16.4 score on a scale STANDARD_DEVIATION 6.7 | 16.4 score on a scale STANDARD_DEVIATION 6.6 | 16.4 score on a scale STANDARD_DEVIATION 6.8 |
| Age, Continuous | 54.9 years STANDARD_DEVIATION 15.2 | 56.3 years STANDARD_DEVIATION 15 | 53.4 years STANDARD_DEVIATION 15.3 |
| Body Mass Index (BMI) | 32.5 kg/m^2 STANDARD_DEVIATION 8.4 | 33.7 kg/m^2 STANDARD_DEVIATION 8.3 | 31.4 kg/m^2 STANDARD_DEVIATION 8.3 |
| Comorbidities Alcohol Abuse | 30 Participants | 13 Participants | 17 Participants |
| Comorbidities Cardiovascular Disease | 65 Participants | 28 Participants | 37 Participants |
| Comorbidities Diabetes | 123 Participants | 59 Participants | 64 Participants |
| Comorbidities Smoker | 66 Participants | 32 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 11 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 264 Participants | 133 Participants | 131 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 3 Participants | 2 Participants |
| Modified Sequential Organ Failure Assessment (mSOFA) Score | 5.5 score on a scale STANDARD_DEVIATION 2.4 | 5.4 score on a scale STANDARD_DEVIATION 2.2 | 5.6 score on a scale STANDARD_DEVIATION 2.5 |
| Necrotizing Soft Tissue Infection (NSTI) Diagnosis Fournier's Gangrene | 83 Participants | 40 Participants | 43 Participants |
| Necrotizing Soft Tissue Infection (NSTI) Diagnosis Gas Gangrene/Myonecrosis | 5 Participants | 4 Participants | 1 Participants |
| Necrotizing Soft Tissue Infection (NSTI) Diagnosis Necrotizing Fasciitis | 191 Participants | 95 Participants | 96 Participants |
| Necrotizing Soft Tissue Infection (NSTI) Diagnosis Other NSTI | 11 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 47 Participants | 24 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants | 10 Participants | 9 Participants |
| Race (NIH/OMB) White | 216 Participants | 110 Participants | 106 Participants |
| Region of Enrollment France | 17 participants | 9 participants | 8 participants |
| Region of Enrollment United States | 273 participants | 138 participants | 135 participants |
| Sepsis Presentation Cardiovascular Organ Failure | 143 Participants | 62 Participants | 81 Participants |
| Sepsis Presentation Respiratory Organ Failure | 30 Participants | 11 Participants | 19 Participants |
| Sex: Female, Male Female | 117 Participants | 59 Participants | 58 Participants |
| Sex: Female, Male Male | 173 Participants | 88 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 24 / 143 | 29 / 147 |
| other Total, other adverse events | 24 / 143 | 25 / 147 |
| serious Total, serious adverse events | 44 / 143 | 40 / 147 |
Outcome results
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.
Time frame: 28 days
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Patients Achieving Necrotizing Infections Clinical Composite Endpoint (NICCE) | mITT Population | 69 Participants |
| Reltecimod (AB103) 0.5 mg/kg | Number of Patients Achieving Necrotizing Infections Clinical Composite Endpoint (NICCE) | US-mITT Population | 67 Participants |
| Placebo | Number of Patients Achieving Necrotizing Infections Clinical Composite Endpoint (NICCE) | mITT Population | 59 Participants |
| Placebo | Number of Patients Achieving Necrotizing Infections Clinical Composite Endpoint (NICCE) | US-mITT Population | 50 Participants |
Comparison: This analysis utilized the mITT analysis population.p-value: 0.135Chi-squared
Comparison: This analysis utilized the US-mITT analysis population.p-value: 0.025Chi-squared
Secondary
Hospital Days
Hospital days refers to the number of days a patient spent time in the hospital.
Time frame: 90 days or until end of follow up
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Hospital Days | 18.0 days |
| Placebo | Hospital Days | 19.5 days |
p-value: 0.512Wilcoxon (Mann-Whitney)
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.
Time frame: 28 days
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Intensive Care Unit (ICU)-Free Days | 20.0 days |
| Placebo | Intensive Care Unit (ICU)-Free Days | 18.0 days |
p-value: 0.401Wilcoxon (Mann-Whitney)
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.
Time frame: 14 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Patients Achieving Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Score of 0 or 1 | 87 Participants |
| Placebo | Number of Patients Achieving Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Score of 0 or 1 | 74 Participants |
p-value: 0.069Chi-squared
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)
Time frame: 90 days
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Patients With a More Favorable or Less Favorable Hospital Discharge Location | More Favorable Discharge Location | 80 Participants |
| Reltecimod (AB103) 0.5 mg/kg | Number of Patients With a More Favorable or Less Favorable Hospital Discharge Location | Less Favorable Discharge Location | 55 Participants |
| Placebo | Number of Patients With a More Favorable or Less Favorable Hospital Discharge Location | More Favorable Discharge Location | 64 Participants |
| Placebo | Number of Patients With a More Favorable or Less Favorable Hospital Discharge Location | Less Favorable Discharge Location | 74 Participants |
p-value: 0.033Chi-squared
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.
Time frame: 28 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Patients With One or More Adverse Events (AEs) | 104 Participants |
| Placebo | Number of Patients With One or More Adverse Events (AEs) | 96 Participants |
Secondary
Number of Patients With One or More Secondary Infections
Number of Patients with One or More Secondary Infections During the Study
Time frame: 28 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Patients With One or More Secondary Infections | 30 Participants |
| Placebo | Number of Patients With One or More Secondary Infections | 32 Participants |
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
Time frame: 28 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Patients With One or More Serious Adverse Events (SAEs) | 44 Participants |
| Placebo | Number of Patients With One or More Serious Adverse Events (SAEs) | 40 Participants |
Secondary
Vasopressor-free Days
Vasopressor-free days refers to the number of days a patient did not receive a vasopressor through Day 28.
Time frame: 28 days
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Vasopressor-free Days | 25.0 days |
| Placebo | Vasopressor-free Days | 25.0 days |
p-value: 0.596Wilcoxon (Mann-Whitney)
Secondary
Ventilator-free Days
Ventilator-free days refers to the number of days a patient was not on a ventilator through Day 28.
Time frame: 28 days
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Ventilator-free Days | 22.0 days |
| Placebo | Ventilator-free Days | 21.0 days |
p-value: 0.195Wilcoxon (Mann-Whitney)
Other Pre-specified
Number of Deaths After Day 14 Through Day 90
Number of deaths after Study Day 14 through Study Day 90
Time frame: 76 days (after Day 14 through Day 90)
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Deaths After Day 14 Through Day 90 | 8 Participants |
| Placebo | Number of Deaths After Day 14 Through Day 90 | 15 Participants |
p-value: 0.14895% CI: [0.23, 1.26]Log Rank
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.
Time frame: 76 days (after Day 14 through Day 90)
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Deaths After Day 14 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5 | 3 Participants |
| Placebo | Number of Deaths After Day 14 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5 | 9 Participants |
p-value: 0.09395% CI: [0.09, 1.25]Log Rank
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.
Time frame: 76 days (after Day 14 through Day 90)
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Deaths After Day 14 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock) | 2 Participants |
| Placebo | Number of Deaths After Day 14 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock) | 7 Participants |
p-value: 0.03195% CI: [0.04, 0.99]Log Rank
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
Time frame: 90 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Deaths From Day 0 Through Day 90 | 24 Participants |
| Placebo | Number of Deaths From Day 0 Through Day 90 | 29 Participants |
p-value: 0.55495% CI: [0.5, 1.46]Log Rank
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.
Time frame: 90 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Deaths From Day 0 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5 | 16 Participants |
| Placebo | Number of Deaths From Day 0 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5 | 19 Participants |
p-value: 0.73695% CI: [0.46, 1.73]Log Rank
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.
Time frame: 90 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Deaths From Day 0 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock) | 14 Participants |
| Placebo | Number of Deaths From Day 0 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock) | 15 Participants |
p-value: 0.35295% CI: [0.35, 1.46]Log Rank
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.
Time frame: 28 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Patients With a Screening Modified Sequential Organ Failure Assessment (mSOFA) Score of at Least 5 Who Achieved NICCE | 38 Participants |
| Placebo | Number of Patients With a Screening Modified Sequential Organ Failure Assessment (mSOFA) Score of at Least 5 Who Achieved NICCE | 25 Participants |
p-value: 0.024Chi-squared
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.
Time frame: 14 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | 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 | 45 Participants |
| Placebo | 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 | 29 Participants |
p-value: 0.007Chi-squared
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.
Time frame: 14 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Score of 0 or 1 | 48 Participants |
| Placebo | Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Score of 0 or 1 | 21 Participants |
p-value: 0.003Chi-squared
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.
Time frame: 28 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reltecimod (AB103) 0.5 mg/kg | Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved NICCE | 38 Participants |
| Placebo | Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved NICCE | 18 Participants |
p-value: 0.034Chi-squared