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

NCT01417780 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ATB-201
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 7

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.

Conditions

Necrotizing Soft Tissue Infections

Outcome Measures

Primary Outcomes (19)

• Number of Subjects With One or More Adverse Events (AEs) During the Treatment Period

  An AE is any untoward medical occurrence in a subject administered study drug and that does not necessarily have a causal relationship with the study drug. An AE could therefore be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug.

  7 days

• Number of Subjects With One or More Serious Adverse Events (SAEs)

  A serious adverse event (SAE) is an AE occurring during any study phase and at any dose of the study drug (AB103 or placebo) that fulfills one or more of the following criteria: * Results in death * Is life-threatening (i.e., the subject was, in the opinion of the Investigator, at immediate risk of death from the event as it occurred) * Requires or prolongs hospitalization * Results in persistent or significant disability or incapacity (i.e., the event causes a substantial disruption of a person's ability to conduct normal life functions) * Is a congenital anomaly or birth defect, or * Is an important and significant medical event.

  28 days

• Alanine Aminotransferase (ALT)

  Screening ALT results, Day 7 ALT results, and change in ALT from screening to Day 7

  Screening and Day 7

• Aspartate Aminotransferase (AST)

  Screening AST results, Day 7 AST results, and change in AST from screening to Day 7

  Screening and Day 7

• Alkaline Phosphatase (ALP)

  Screening ALP results, Day 7 ALP results, and change in ALP from screening to Day 7

  Screening and Day 7

• Total Bilirubin (Tbili)

  Screening Tbili results, Day 7 Tbili results, and change in Tbili from screening to Day 7

  Screening and Day 7

• Serum Creatinine (sCr)

  Screening sCr results, Day 7 sCr results, and change in sCr from screening to Day 7

  Screening and Day 7

• Albumin (Alb)

  Screening Alb results, Day 7 Alb results, and change in Alb from screening to Day 7

  Screening and Day 7

• Hemoglobin (Hgb)

  Screening Hgb results, Day 7 Hgb results, and change in Hgb from screening to Day 7

  Screening and Day 7

• Total White Blood Cell (WBC) Count

  Screening WBC results, Day 7 WBC results, and change in WBC from screening to Day 7

  Screening and Day 7

• Platelet (PLT) Count

  Screening PLT results, Day 7 PLT results, and change in PLT from screening to Day 7

  Screening and Day 7

• International Normalized Ratio (INR)

  Screening INR results, Day 7 INR results, and change in INR from screening to Day 7. In general, the higher the INR value, the longer it takes for blood to form a clot.

  Screening and Day 7

• QT Interval With Fridericia's Correction (QTcF)

  Pre-dose QTcF, post-dose QTcF, change in QTcF from pre-dose to post-dose

  Pre-dose and up to 24 hours post-dose

• Categorical Change in QTcF

  Number and percentage of patients with a change in QTcF of \> 30 msec; number and percentage of patients with a change in QTcF of \> 60 msec

  Pre-dose and up to 24 hours post-dose

• Area Under the Plasma Concentration Versus Time Curve (AUC)

  Area under the plasma concentration versus time curve (AUC) from time zero to infinity following a single dose of study drug, obtained by noncompartmental methods. It is an integrated measure of study drug plasma exposure.

  Prior to infusion, at mid infusion time, end of infusion, and at 2, 5, 10, 20, 30, 60 min and 120 minutes after completion of the IV infusion of study drug.

• Maximum Plasma Concentration (Cmax)

  Maximum plasma concentration (observed)

  Prior to infusion, at mid infusion time, end of infusion, and at 2, 5, 10, 20, 30, 60 min and 120 minutes after completion of the IV infusion of study drug.

• Apparent Terminal Plasma Half-life (T1/2)

  Apparent terminal plasma half-life (T1/2) is the amount of time for plasma concentrations to decline by 50%.

  Prior to infusion, at mid infusion time, end of infusion, and at 2, 5, 10, 20, 30, 60 min and 120 minutes after completion of the IV infusion of study drug.

• Clearance (CL)

  Clearance (CL) is the volume of plasma completely cleared of drug per unit of time.

  Prior to infusion, at mid infusion time, end of infusion, and at 2, 5, 10, 20, 30, 60 min and 120 minutes after completion of the IV infusion of study drug.

• Apparent Volume of Distribution Under Steady State Conditions (Vss)

  Apparent volume of distribution under steady state conditions (Vss) based on drug concentration in plasma

  Prior to infusion, at mid infusion time, end of infusion, and at 2, 5, 10, 20, 30, 60 min and 120 minutes after completion of the IV infusion of study drug.

Secondary Outcomes (6)

• C-reactive Protein (CRP)

  Screening and Day 7

• Day 14 Sequential Organ Failure Assessment (SOFA) Score

  14 days

• Day 14 Sequential Organ Failure Assessment (SOFA) Score Less Than or Equal to 1

  14 days

• Hospital Length of Stay (LOS)

  28 days

• Intensive Care Unit-free Days (ICU-free Days)

  28 days

Study Arms (3)

AB103 0.25 mg/kg

ACTIVE COMPARATOR

Drug: AB103

AB103 0.5 mg/kg

ACTIVE COMPARATOR

Drug: AB103

Placebo

PLACEBO COMPARATOR

Normal saline (0.9% sodium chloride)

Drug: Placebo

Interventions

AB103 DRUG

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

Also known as: p2TA

AB103 0.25 mg/kg; AB103 0.5 mg/kg

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Atox Bio Ltd: lead

Study Sites (7)

University of Southern California Los Angeles

Los Angeles, California, United States

Location

San Francisco General Hospital

San Francisco, California, United States

Location

University of Florida

Gainesville, Florida, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Oregon Health and Science University

Portland, Oregon, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Related Publications (2)

• 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.

  PMID: 24740134 RESULT

• 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

  RESULT

MeSH Terms

Interventions

AB103

Results Point of Contact

• Title: Wayne M Dankner, MD, Chief Medical Officer
• Organization: Atox Bio, Ltd.

wayned@atoxbio.com

1 919-219-6377

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2011
• First Posted: August 16, 2011
• Study Start: December 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: August 18, 2021
• Results First Posted: August 18, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)