Phase III Efficacy and Safety Study of AB103 in the Treatment of Patients With Necrotizing Soft Tissue Infections
Condition: Necrotizing Soft Tissue Infections; Necrotizing Fasciitis; Fournier's Gangrene
MeSH terms: Infections; Communicable Diseases; Soft Tissue Infections; Fournier Gangrene; Fasciitis; Fasciitis, Necrotizing; Gangrene
Intervention: AB103 0.5 mg/kg; NaCl 0.9%
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 290.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: AB103; Necrotizing fasciitis

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.
    

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