Evaluation of Safety, PK and Immunomodulatory Effects of AB103 in Necrotizing Soft Tissue Infections Patients
Condition: Necrotizing Soft Tissue Infections
MeSH terms: Infections; Communicable Diseases; Soft Tissue Infections
Intervention: AB103; Placebo
Intervention description: AB103 0.25 mg/kg or 0.5 mg/kg administered as a single IV infusion; Normal saline (0.9% sodium chloride) administered as a single IV infusion
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      A study to evaluate the safety and pharmacokinetics profile of different doses of AB103
      administered to patients diagnosed with Necrotizing Soft Tissue Infections that are scheduled
      for an urgent surgical intervention as part of their standard of care.
    

Eligibility criteria:

        Inclusion Criteria

          -  Clinical diagnosis of NSTI due to bacterial infection (Necrotizing Fasciitis, Group A
             streptococcal infection or non group A streptococcal infection, Fournier's gangrene,
             Bacterial synergistic gangrene, Synergistic Necrotizing Cellulitis, Clostridial gas
             gangrene/ myonecrosis) that may be supported by specific signs and symptoms, e.g.
             tense edema outside area of compromised skin, pain disproportionate to appearance,
             skin discoloration, ecchymosis, blisters/bullae, necrosis, tense edema, crepitus
             and/or subcutaneous gas AND a decision for urgent surgical exploration and
             debridement;

          -  Patient who did not receive the study drug prior to the surgery need to have a
             definite diagnosis of NSTI confirmed surgically (e.g. presence of necrotic tissue,
             thrombosed vessels in the subcutaneous tissue, lack of bleeding and "dishwater"
             (cloudy, thin, gray) fluid) in order to get the drug during or after operation;

          -  IV drug administration within 6 hours from the clinical diagnosis and from the
             documented decision to have an urgent surgical exploration and debridement;

          -  Signed and dated ICF as defined by the IRB and, if applicable, California Bill of
             Rights. By signing the ICF, the patient agrees to release any medical records pursuant
             to current Health Insurance Portability and Accountability Act (HIPAA) Guidelines. If
             patient is unable to comprehend or sign the ICF, patient's legally acceptable
             representative may sign the ICF;

        Exclusion Criteria

          -  Age < 18 years;

          -  Weight > 150 Kg / 330 pounds;

          -  Pregnant or lactating women; Female of childbearing potential, the patient must have a
             negative beta subunit hCG pregnancy test immediately prior to study entry (performed
             by urine or blood test, whichever is faster);

          -  Patient who has been operated at least once for the current NSTI infection and had a
             curative deep tissue debridement (diagnostic surgery is allowed to enter into the
             study);

          -  Known HIV infection with CD4 count < 200 cells/mm3 or < 14% of all lymphocytes;

          -  Diabetic patients with below ankle infection;

          -  Patients with overt peripheral vascular disease in the involved area - condition
             associated with ischemic ulcers and /or symptoms of inadequate vascular supply (e.g.
             intermittent claudication) where limb amputation is considered likely within 7 days;

          -  Current status of: a. Mean arterial pressure < 50 mmHg and/or systolic blood pressure
             < 70 mmHg despite treatment with vasopressors and/or 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 > 3) or d. thrombocytopenia (platelet count < 20,000)
             that does not partially correct with administration of appropriate factors, or e.
             likely severe neurological impairment secondary to cardiac arrest.

          -  Patients with cardiac arrest requiring cardiopulmonary resuscitation within the past
             30 days;

          -  Patient is not expected to survive 30 days because of underlying medical condition,
             such as poorly controlled neoplasm (e.g. Stage III or IV cancer);

          -  Any concurrent medical condition, which in the opinion of the investigator, may
             compromise their safety or the objectives of the study or the patient will not benefit
             from treatment, (e.g. end stage organ disease {CHF {NYHA class III-IV}, COPD {stage
             III-IV}, Liver dysfunction {Childs-Pugh class C}, Renal dysfunction {Dialysis}),
             immunosuppression, receiving or about to receive chemotherapy or known severe
             neutropenia < 1,000 cells/mm3;

          -  Patients with Necrotizing Soft Tissue Infection post intra-abdominal operation;

          -  Patient with burn wounds;

          -  Patient or patient's family are not committed to aggressive management of the
             patient's condition, or the combination of necrotizing skin infection and underlying
             illness makes it unlikely that life support will be maintained;

          -  Previous enrolment in an previous clinical trial involving investigational drug or a
             medical device within 30 days before provision of written informed consent for the
             study or within five half lives of the investigational drug, whichever is longer;