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CompletedNCT02469857ACCUTEUpdated Oct 5, 2021Results posted

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

A Phase 3 interventional study of AB103 0.5 mg/kg and NaCl 0.9% in Necrotizing Soft Tissue Infections, Necrotizing Fasciitis and Fournier's Gangrene, sponsored by Atox Bio Ltd. Completed at 71 sites in 2 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2021-10-05.

Sponsored by Atox Bio Ltd · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
290
Allocation
Randomized
Ages
12 Years and older
Sex
All
01

Study 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 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.

02

Conditions studied

  • Necrotizing Soft Tissue Infections
  • Necrotizing Fasciitis
  • Fournier's Gangrene

Keywords

  • AB103
  • Necrotizing fasciitis
03

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

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

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 exclusion criteria
  6. Patient with burn wounds;
  7. Current condition of: (a) Inability to maintain a mean arterial pressure > 50 mmHg and/or systolic blood pressure > 70 mmHg for at least 1 hour prior to screening despite the presence of vasopressors and IV fluids or (b) a patient with respiratory failure such that an SaO2 of 80% cannot be achieved or (c) a patient with refractory coagulopathy (INR >5) or thrombocytopenia (platelet count \<20,000) that does not partially correct with administration of appropriate factors or blood products;
  8. Chronic neurological impairment that leads to a neuro mSOFA component ≥2;
  9. Recent cerebrovascular accident in the last 3 months;
  10. Patients with cardiac arrest requiring cardiopulmonary resuscitation within the past 30 days;
  11. Patient is not expected to survive throughout 28 days of study due to underlying medical condition, such as poorly controlled neoplasm;
  12. Patient or patient's family are not committed to aggressive management of the patient's condition;

  13. Any concurrent medical condition, which in the opinion of the Investigator, may compromise the safety of the patient or the objectives of the study or the patient will not benefit from treatment such as:

    • 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;
  14. Known HIV infection with CD4 (cluster of differentiation 4) count \< 200 cells/mm3 or \< 14% of all lymphocytes;
  15. Patients with known chronic kidney disease (documented pre-illness creatinine value(s) ≥2.0) or patients receiving renal replacement therapy for chronic kidney disease;
  16. Patients that are treated with continuous hemofiltration (e.g. Continuous Veno-Venous Hemofiltration) for acute kidney dysfunction, not due to NSTI, starting prior to study drug administration;
  17. Pregnant or lactating women;
  18. Previous enrollment in a clinical trial involving investigational drug or a medical device within 30 days;
  19. Previous enrollment in this protocol, ATB-202 or the Phase 2 trial of AB103, ATB-201.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
290 participants (actual)

Study arms

  • Experimental
    AB103 0.5 mg/kg

    AB103 0.5 mg/kg, IV, single dose

    Drug: AB103 0.5 mg/kg

  • Placebo comparator
    NaCl 0.9%

    NaCl 0.9%, IV, single dose

    Other: NaCl 0.9%

Interventions

  • DrugAB103 0.5 mg/kg

    Also known as: reltecimod

  • OtherNaCl 0.9%

    Also known as: Normal saline

05

What researchers measure

Primary outcomes

  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.

    Time frame: 28 days

Secondary outcomes

  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.

    Time frame: 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

    Time frame: 28 days

  3. 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

  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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 28 days

  8. 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

  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)

    Time frame: 90 days

Other outcomes

  1. 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

  2. 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)

  3. 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

  4. 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)

  5. 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

  6. 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)

  7. 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

  8. 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

  9. 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

  10. 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

06

Results

Posted Oct 5, 2021

Participant flow

Participant flow — Overall Study
MilestoneReltecimod (AB103) 0.5 mg/kgPlacebo
Started143147
Completed118115
Not completed2532
Withdrew: Death2429
Withdrew: Discontinuation13

Outcome measures

PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of Patients Achieving Necrotizing Infections Clinical Composite Endpoint (NICCE)
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
mITT Population6959
US-mITT Population6750
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Chi-squared · p = 0.135
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Chi-squared · p = 0.025
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Patients With One or More Adverse Events (AEs)
ParticipantsAB103 0.5 mg/kgPlacebo
Number of Patients With One or More Adverse Events (AEs)10496
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Patients With One or More Serious Adverse Events (SAEs)
ParticipantsAB103 0.5 mg/kgPlacebo
Number of Patients With One or More Serious Adverse Events (SAEs)4440
SecondaryNumber of Patients With One or More Secondary Infections

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

Time frame:
28 days
Reported as:
Count of participants · Participants
Number of Patients With One or More Secondary Infections
ParticipantsAB103 0.5 mg/kgPlacebo
Number of Patients With One or More Secondary Infections3032
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Patients Achieving Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Score of 0 or 1
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
Number of Patients Achieving Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Score of 0 or 18774
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Chi-squared · p = 0.069
SecondaryIntensive 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
Reported as:
Median · days
Intensive Care Unit (ICU)-Free Days
daysReltecimod (AB103) 0.5 mg/kgPlacebo
Intensive Care Unit (ICU)-Free Days20.0 (0 to 28)18.0 (0 to 28)
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.401
SecondaryVentilator-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
Reported as:
Median · days
Ventilator-free Days
daysReltecimod (AB103) 0.5 mg/kgPlacebo
Ventilator-free Days22.0 (0 to 28)21.0 (0 to 28)
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.195
SecondaryVasopressor-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
Reported as:
Median · days
Vasopressor-free Days
daysReltecimod (AB103) 0.5 mg/kgPlacebo
Vasopressor-free Days25.0 (0 to 28)25.0 (0 to 28)
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.596
SecondaryHospital 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
Reported as:
Median · days
Hospital Days
daysReltecimod (AB103) 0.5 mg/kgPlacebo
Hospital Days18.0 (1 to 103)19.5 (2 to 135)
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.512
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Patients With a More Favorable or Less Favorable Hospital Discharge Location
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
More Favorable Discharge Location8064
Less Favorable Discharge Location5574
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Chi-squared · p = 0.033
Other pre-specifiedNumber 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
Reported as:
Count of participants · Participants
Number of Deaths From Day 0 Through Day 90
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
Number of Deaths From Day 0 Through Day 902429
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Log Rank · p = 0.554 · Hazard ratio (hr): 0.85 · 95% CI 0.50 to 1.46
Other pre-specifiedNumber 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)
Reported as:
Count of participants · Participants
Number of Deaths After Day 14 Through Day 90
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
Number of Deaths After Day 14 Through Day 90815
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Log Rank · p = 0.148 · Hazard ratio (hr): 0.54 · 95% CI 0.23 to 1.26
Other pre-specifiedNumber 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
Reported as:
Count of participants · Participants
Number of Deaths From Day 0 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
Number of Deaths From Day 0 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 51619
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Log Rank · p = 0.736 · Hazard ratio (hr): 0.89 · 95% CI 0.46 to 1.73
Other pre-specifiedNumber 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)
Reported as:
Count of participants · Participants
Number of Deaths After Day 14 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 5
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
Number of Deaths After Day 14 Through Day 90 Among Patients With a Screening mSOFA Score of at Least 539
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Log Rank · p = 0.093 · Hazard ratio (hr): 0.34 · 95% CI 0.09 to 1.25
Other pre-specifiedNumber 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
Reported as:
Count of participants · Participants
Number of Deaths From Day 0 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock)
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
Number of Deaths From Day 0 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock)1415
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Log Rank · p = 0.352 · Hazard ratio (hr): 0.71 · 95% CI 0.35 to 1.46
Other pre-specifiedNumber 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)
Reported as:
Count of participants · Participants
Number of Deaths After Day 14 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock)
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
Number of Deaths After Day 14 Through Day 90 Among Patients With Baseline Cardiovascular Failure (Shock)27
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Log Rank · p = 0.031 · Hazard ratio (hr): 0.21 · 95% CI 0.04 to 0.99
Other pre-specifiedNumber 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
Reported as:
Count of participants · Participants
Number of Patients With a Screening Modified Sequential Organ Failure Assessment (mSOFA) Score of at Least 5 Who Achieved NICCE
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
Number of Patients With a Screening Modified Sequential Organ Failure Assessment (mSOFA) Score of at Least 5 Who Achieved NICCE3825
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Chi-squared · p = 0.024
Other pre-specifiedNumber 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
Reported as:
Count of participants · Participants
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
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
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 14529
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Chi-squared · p = 0.007
Other pre-specifiedNumber 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
Reported as:
Count of participants · Participants
Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved NICCE
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved NICCE3818
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Chi-squared · p = 0.034
Other pre-specifiedNumber 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
Reported as:
Count of participants · Participants
Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Score of 0 or 1
ParticipantsReltecimod (AB103) 0.5 mg/kgPlacebo
Number of Patients With Baseline Cardiovascular Failure (Shock) Who Achieved Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Score of 0 or 14821
Statistical analysis
  • Reltecimod (AB103) 0.5 mg/kg vs Placebo · Chi-squared · p = 0.003

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Reltecimod (AB103) 0.5 mg/kg24/143 (16.8%)44/143 (30.8%)24/143 (16.8%)
Placebo29/147 (19.7%)40/147 (27.2%)25/147 (17%)
Most frequent serious events
Showing 10 of 67
Most frequent serious events
EventReltecimod (AB103) 0.5 mg/kgPlacebo
Cardiac arrestCardiac disorders4/1434/147
Acute kidney injuryRenal and urinary disorders4/1432/147
Acute respiratory distress syndromeRespiratory, thoracic and mediastinal disorders2/1434/147
Pulseless electrical activityCardiac disorders3/1432/147
Necrotizing soft tissue infectionInfections and infestations3/1433/147
PneumoniaInfections and infestations3/1431/147
Septic shockInfections and infestations3/1432/147
Acute myocardial infarctionCardiac disorders2/1433/147
Atrial fibrillationCardiac disorders2/1433/147
Organ failureGeneral disorders2/1432/147
Most frequent other events
Most frequent other events
EventReltecimod (AB103) 0.5 mg/kgPlacebo
PneumoniaInfections and infestations5/14311/147
AnemiaBlood and lymphatic system disorders8/1436/147
Atrial fibrillationCardiac disorders7/1438/147
DiarrheaGastrointestinal disorders6/1438/147

Baseline characteristics

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.

Age, Continuous
Age, Continuous(years)Reltecimod (AB103) 0.5 mg/kgPlaceboTotal
Mean53.4 ± 15.356.3 ± 15.054.9 ± 15.2
Sex: Female, Male
Sex: Female, Male(Participants)Reltecimod (AB103) 0.5 mg/kgPlaceboTotal
Female5859117
Male8588173
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Reltecimod (AB103) 0.5 mg/kgPlaceboTotal
Hispanic or Latino101121
Not Hispanic or Latino131133264
Unknown or Not Reported235
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Reltecimod (AB103) 0.5 mg/kgPlaceboTotal
American Indian or Alaska Native325
Asian202
Native Hawaiian or Other Pacific Islander011
Black or African American232447
White106110216
More than one race000
Unknown or Not Reported91019
Region of Enrollment
Region of Enrollment(participants)Reltecimod (AB103) 0.5 mg/kgPlaceboTotal
United States135138273
France8917
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)Reltecimod (AB103) 0.5 mg/kgPlaceboTotal
Mean31.4 ± 8.333.7 ± 8.332.5 ± 8.4
Necrotizing Soft Tissue Infection (NSTI) Diagnosis
Necrotizing Soft Tissue Infection (NSTI) Diagnosis(Participants)Reltecimod (AB103) 0.5 mg/kgPlaceboTotal
Necrotizing Fasciitis9695191
Fournier's Gangrene434083
Gas Gangrene/Myonecrosis145
Other NSTI3811
Comorbidities
Comorbidities(Participants)Reltecimod (AB103) 0.5 mg/kgPlaceboTotal
Diabetes6459123
Cardiovascular Disease372865
Smoker343266
Alcohol Abuse171330

4 further baseline measures are reported on the registry.

07

Study locations

71 sites
  • University of Alabama at Birmingham
    Birmingham, Alabama 35294, United States
  • Maricopa Medical Center
    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, 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
    Saint 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
  • Hộpital 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
08

References and documents

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 ↗

Study documents

  • Study protocol · Aug 23, 2018
  • Statistical analysis plan · Sep 24, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT02469857
Lead sponsor
Atox Bio Ltd
Collaborators
Biomedical Advanced Research and Development Authority
Responsible party
Sponsor
First posted
Jun 12, 2015
Start date
Dec 1, 2015
Primary completion
Aug 18, 2019
Completion
Oct 18, 2019
Results posted
Oct 5, 2021
Last update
Oct 5, 2021

Study contacts

Wayne M Dankner, MD
study director · Atox Bio Ltd
Eileen M Bulger, MD
principal investigator · Harborview Injury Prevention and Research Center

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2021. You cannot join it, but the record below documents what was studied.

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