Evaluation of Safety, PK and Immunomodulatory Effects of AB103 in Necrotizing Soft Tissue Infections Patients

NCT ID: NCT01417780

Last Updated: 2021-08-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2012-09-30

Brief 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.

Detailed Description

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. The primary study hypothesis is that AB-103 can be administered safely to the patients presenting with Necrotizing Soft Tissue Infections.

Secondary endpoints are efficacy by exploratory descriptive analyses of specific efficacy endpoints from three outcome domains to demonstrate treatment benefit of AB103 in comparison to placebo in patients with Necrotizing Soft Tissue Infections. The efficacy domains are:

1. Clinical status domain

2. Pharmacoeconomics domain

3. Systemic and local inflammatory biomarker domain

Conditions

Necrotizing Soft Tissue Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

AB103 0.25 mg/kg

Group Type: ACTIVE_COMPARATOR

AB103

Intervention Type: DRUG

AB103 0.25 mg/kg or 0.5 mg/kg administered as a single IV infusion

AB103 0.5 mg/kg

Group Type: ACTIVE_COMPARATOR

AB103

Intervention Type: DRUG

AB103 0.25 mg/kg or 0.5 mg/kg administered as a single IV infusion

Placebo

Normal saline (0.9% sodium chloride)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Normal saline (0.9% sodium chloride) administered as a single IV infusion

Interventions

AB103

AB103 0.25 mg/kg or 0.5 mg/kg administered as a single IV infusion

Intervention Type: DRUG

Placebo

Normal saline (0.9% sodium chloride) administered as a single IV infusion

Intervention Type: DRUG

Other Intervention Names

p2TA

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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Atox Bio Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Southern California Los Angeles

Los Angeles, California, United States

San Francisco General Hospital

San Francisco, California, United States

University of Florida

Gainesville, Florida, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Harborview Medical Center

Seattle, Washington, United States

Countries

United States

References

Bulger EM, Maier RV, Sperry J, Joshi M, Henry S, Moore FA, Moldawer LL, Demetriades D, Talving P, Schreiber M, Ham B, Cohen M, Opal S, Segalovich I, Maislin G, Kaempfer R, Shirvan A. A Novel Drug for Treatment of Necrotizing Soft-Tissue Infections: A Randomized Clinical Trial. JAMA Surg. 2014 Jun;149(6):528-36. doi: 10.1001/jamasurg.2013.4841.

Reference Type: RESULT

PMID: 24740134 (View on PubMed)

Bulger EM, Maislin G, Dankner W, May A, Edgar R, Shirvan A. Critical Care Medicine, January 2018,46(1):327. Abstract 682: Early Plasma Cytokine Levels Correlate With Outcome in Necrotizing Soft Tissue Infections. https://journals.lww.com/ccmjournal/Citation/2018/01001/682

Reference Type: RESULT

Other Identifiers

ATB-201

Identifier Type: -

Identifier Source: org_study_id