Observational Study Evaluating Clinical Benefit and Safety of AIGIV (ANTHRASIL®) in Patients With Systemic Anthrax

An Observational Clinical Study of AIGIV Use in Sporadic Cases of Systemic Anthrax

This study will evaluate safety and clinical benefit of AIGIV used for treatment of patients with systemic anthrax. The study is designed to collect information on safety, clinical benefit (such as extent of anthrax illness and survival) and serum concentrations of AIGIV (for AIGIV pharmacokinetics) and anthrax toxins from sporadic cases of systemic anthrax patients treated with AIGIV.

Study Overview

• Status: Not yet recruiting
• Conditions: Anthrax
• Intervention / Treatment: Drug: AIGIV

Detailed Description

This study is a post-marketing requirement from the FDA to evaluate safety and clinical benefit of AIGIV administered to systemic anthrax patients as part of their medical care after exposure to Bacillus anthracis (anthrax exposure can be via inhalation, ingestion, injection). Study information (i.e. data on safety and clinical benefit evaluation of AIGIV up to Day 30 following administration) and patient samples (for assessment of AIGIV pharmacokinetics and anthrax toxin levels) will be collected (up to Day 7 following AIGIV administration) prospectively to the extent possible; however, in some cases data may be collected retrospectively (including scavenged patient samples for assessment of serum AIGIV concentration and anthrax toxin levels). Therefore, both prospective and retrospective data collection are allowed in this study to maximize the amount of information obtained from systemic anthrax patients who have been treated with AIGIV.

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

• Study Contact: Name: Gideon Akintunde, MD; Phone Number: 204 275 4060; Email: AkintundG@ebsi.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Anthrax patients who have received AIGIV.

Description

Inclusion Criteria:

• Confirmed or suspected systemic anthrax patients in the USA or other jurisdictions (if feasible) treated with AIGIV provided by the Centers for Disease Control and Prevention (CDC).
• Systemic anthrax defined as a clinically compatible case of gastrointestinal, injectional, or inhalational anthrax; anthrax meningitis or bacteremia; or cutaneous anthrax with systemic effects (i.e. tachycardia, tachypnea, hypotension, hyperthermia, hypothermia, leukocytosis) or with lesions that involve the head, neck or upper torso, or are large, bullous, multiple, or surrounded by significant edema PLUS confirmation by one of the following:

Epidemiologically linked to a documented anthrax environmental exposure. Laboratory confirmation by isolation of B. anthracis from an affected tissue or site.

Demonstration of B. anthracis antigens in tissues by immunohistochemical staining using both B. anthracis cell wall and capsule monoclonal antibodies.

Evidence of B. anthracis DNA; for example, by polymerase chain reaction (PCR) in specimens collected from a normally sterile site (such as blood or cerebrospinal fluid (CSF)) or lesion of other affected tissue(s) (skin, pulmonary, reticuloendothelial, or gastrointestinal).

QuickELISA™ Anthrax-PA kit manufactured by Immunetics, Inc. for detection of anti-PA antibodies in serum, plasma, and pleural/ascitic fluid.

RedLine Alert™ test manufactured by Tetracore, Inc., for identification of B. anthracis colonies.

• Informed consent/assent (as applicable).

Exclusion Criteria:

• There are no exclusion criteria for subjects enrolling in this study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
AIGIV; Anthrax patients who have been administered AIGIV (ANTHRASIL®) as per licensed US prescribing information.	Drug: AIGIV; Anthrax Immune Globulin Intravenous (Human); Other Names: ANTHRASIL®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of AIGIV clinical benefit by overall mortality rate	Mortality rate (incidence of death) in patients with confirmed diagnosis of systemic anthrax treated with AIGIV	Up to Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of AIGIV safety by incidence of serious adverse drug reactions and serious suspected adverse drug reactions	Combined incidence of serious adverse drug reactions (i.e. serious adverse events related to AIGIV administration) and serious suspected adverse drug reactions (i.e. serious adverse events that occur during or within 24 hours following AIGIV administration) in individuals treated with AIGIV	Up to Day 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cause-specific mortality rate	Number of deaths assigned to a specific cause in patients with confirmed diagnosis of systemic anthrax treated with AIGIV	Up to Day 30
Mortality rate stratified by number of AIGIV doses administered	Number of deaths stratified by number of AIGIV doses (single versus multiple doses) in patients with confirmed diagnosis of systemic anthrax treated with AIGIV	Up to Day 30
Mortality rate stratified by AIGIV treatment time from symptom onset	Number of deaths stratified by AIGIV treatment time from symptom onset (early versus late onset of symptoms) in patients with confirmed diagnosis of systemic anthrax	Up to Day 30
Mortality rate stratified by acute physiologic assessment and chronic health evaluation (APACHE) II score at baseline	Number of deaths stratified by APACHE II score at baseline in patients with confirmed diagnosis of systemic anthrax treated with AIGIV	Up to Day 30
Duration of hospitalization	Length of hospitalization in patients with confirmed diagnosis of systemic anthrax treated with AIGIV	Up to Day 30
Duration of intensive care unit (ICU) hospitalization	Length of ICU stay in patients with confirmed diagnosis of systemic anthrax treated with AIGIV	Up to Day 30
Incidence of ICU hospitalization	Number of patients with confirmed diagnosis of systemic anthrax treated with AIGIV admitted to ICU	Up to Day 30
Duration of mechanical ventilation	Length of mechanical ventilation in patients with confirmed diagnosis of systemic anthrax treated with AIGIV	Up to Day 30
Evaluation of sequential organ failure assessment (SOFA) score	Increase in sequential organ failure assessment (SOFA) score from baseline in patients with confirmed diagnosis of systemic anthrax treated with AIGIV. Total SOFA score can range from 0 to 24; increase in total SOFA score suggests worse clinical outcome prediction.	Up to Day 14
Assessment of AIGIV pharmacokinetics	Serum concentration of AIGIV over time in patients with confirmed diagnosis of systemic anthrax treated with AIGIV to determine pharmacokinetic parameters such as maximum serum concentration, area under the concentration versus time (i.e. level of AIGIV circulating over time) and clearance	Up to Day 7
Assessment of anthrax toxin levels (protective antigen and lethal factor)	Levels of anthrax toxins (protective antigen and lethal factor) over time in patients with confirmed diagnosis of systemic anthrax treated with AIGIV	Up to Day 7

Collaborators and Investigators

• Sponsor: Emergent BioSolutions
• Collaborators: Department of Health and Human Services; Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Brandon Essink, MD

Study record dates

Study Major Dates

• Study Start (Estimated): February 11, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: June 15, 2018
• First Submitted That Met QC Criteria: June 15, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Bacterial infection; Anthrax; Bacillus anthracis; AIGIV; Anthrax immune globulin; Anti toxin; Polyclonal antibodies
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Bacillaceae Infections; Anthrax
• Other Study ID Numbers: AX-003B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No