This is a Phase III, randomized, double-blind, placebo controlled, parallel-group multicenter study to determine the efficacy and safety of AB103 as compared to placebo, in patients diagnosed with necrotizing soft tissue infections (NSTI).

Phase 1

• Conditions: ecrosis of soft tissue infections (NSTI); MedDRA version: 20.0 Level: PT Classification code 10065769 Term: Soft tissue necrosis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; MedDRA version: 20.0 Level: LLT Classification code 10017068 Term: Fournier's gangrene System Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.1 Level: PT Classification code 10028885 Term: Necrotising fasciitis System Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2018-001125-15-FR
• Lead Sponsor: Atox Bio

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-05-14
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 290

Inclusion Criteria

1. Age: =18 years
2. Surgical confirmation of NSTI by attending surgeon (e.g. presence of necrotic tissue, thrombosed vessels in the subcutaneous tissue, lack of bleeding and dishwater” (cloudy, thin, gray) fluid) due to presumed bacterial infection (necrotizing cellulitis (most commonly group A strep), necrotizing fasciitis, necrotizing myositis and myonecrosis, NSTI of the perineum, bacterial synergistic gangrene, Clostridial gas gangrene) 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).
•Patients with NSTI following intra-abdominal operation are eligible if adequate source control of intra-abdominal process has been established
3. mSOFA score =3 (in any one or combination of the 5 major components of SOFA score with any one organ component having a score of at least 2: cardiovascular, respiratory, renal, coagulation, CNS), measured as close as possible to the first debridement, (but before first debridement is performed).
4. 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).
5. If a woman is of childbearing potential, she must consistently use an acceptable method of contraception from baseline through Day 28. Acceptable birth control methods include oral contraceptive medication, an intrauterine device (IUD), an injectable contraceptive (such as Depo-Provera®), a birth control patch, a barrier method (such as condom or diaphragm with spermicide) or abstinence.
oNon-childbearing potential is defined as current tubal ligation, hysterectomy, or ovariectomy or post-menopause (1 year without menses with an appropriate clinical profile at the appropriate age e.g. >45 years).
6. 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.
7. 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 245
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

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 (patients who underwent prior diagnostic minor surgery are allowed to enter into the study);
3. Patients with overt peripheral vascular disease in the involved area - associated with ischemic wounds/ulcers or gangrene, and /or other significant symptoms of inadequate vascular supply or where limb amputation is considered likely within 7 days due to the peripheral vascular disease;
4. Diabetic patients with peripheral vascular disease who present with below the ankle infection;
5. Removed
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 (e.g. Stage III or IV cancer);
12. 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;
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:
oCHF {NYHA class III-IV}
oSevere COPD {GOLD stage III-IV. or chronic hypoxemia (PaO2 <55 mmHg) on room air, or chronic use of home ventilation, or unable to climb stairs or perform household duties due to chronic obstructive disease resulting in severe exercise restriction, or use of continuous home oxygen prior to hospital admission (sleep apnoea treated with continuous positive airway pressure or biphasic positive airway pressure oxygen during sleep is acceptable)}
oLiver dysfunction {Childs-Pugh class C}
oImmunosuppression (see Appendix F, Section 15.6 for list of excluded immunosuppressive medications)
oNeutropenia < 1,000 cells/mm3not due to the underlying infection
oIdiopathic Thrombocytopenic Purpura (ITP)
oReceiving or about to receive chemotherapy or biologic anti-cancer treatment although hormonal manipulation therapies for breast and prostate malignancies are permitted
oHematological and lymphatic malignancies in the last 5 years
14. Known HIV infection with CD4 count < 200 cells/mm3 or < 14% of all lymphocytes;
15. Patients with known chronic kidney disease (documented pre-illness creatinine value(s)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified