Clinical Benefit, Safety and PK of Raxibacumab in Subjects Exposed to Bacillus Anthracis

Study Overview
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Brief Summary
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This field study is designed such that it may be implemented for any individual who has been administered raxibacumab for treatment of anthrax or for post-exposure prophylaxis including sporadic cases, small anthrax incidents and/or a mass event. This study is designed to describe the clinical effectiveness (including course of illness and survival), safety profile, and raxibacumab pharmacokinetics (PK) from patients who are treated with raxibacumab as part of their clinical care following exposure to B. anthracis. Study data and samples for PK and other investigational research will be collected prospectively to the extent possible at pre-specified time points. However, because of the logistical complexities that would likely accompany a mass anthrax event, most data in this study is anticipated to be collected retrospectively. During such a mass anthrax event scavenged blood samples will be utilized where possible to maximize sample analyses for PK and other investigational parameters. Therefore, both retrospective and prospective data collection are allowed in this protocol in order to maximize the amount of information obtained in subjects who have been administered raxibacumab. This field study will be the first opportunity to collect data on B. anthracis-exposed patients treated with raxibacumab, to better understand the clinical benefit and safety of the drug and to further inform patient care and treatment choices for management of anthrax

Detailed Description
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The protocol is a post-marketing requirement from the FDA to evaluate the clinical benefit, safety and pharmacokinetic of raxibacumab administered to patients as part of their medical care following exposure to Bacillus anthracis.

Official Title
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A Phase 4, Open-label Field Study (200137) to Evaluate the Clinical Benefit, Safety and Pharmacokinetics in Subjects Treated With Raxibacumab (GSK3068483) Following Exposure to Bacillus Anthracis

Conditions
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Infections, Bacterial

Intervention / Treatment
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* Biological: Collection of samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women-including pregnant and lactating women, men, and children of all ages who receive treatment with raxibacumab as part of their clinical care for anthrax infection or for post-exposure prophylaxis will be eligible to enroll in this study. Subjects willing and able to adhere to the procedures stated in the protocol Subjects or legally acceptable representative of minors and unconscious adults willing and able to give written informed consent to participate in the study. Exclusion Criteria: There are no exclusion criteria for subjects enrolling in this study.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Raxibacumab arm<br>This is an open-label, single arm study. The study will be implemented for subjects who receive FDA-approved raxibacumab as part of medical treatment of anthrax or for post-exposure prophylaxis. Intervention: Sampling of subjects or use of subjects salvaged standard of care samples may be considered for the following assessments (if available/applicable): pregnancy test, pharmacokinetics (PK) sampling, protective antigen, toxin neutralizing antibody (TNA), anti-raxibacumab antibodies. | Biological: Collection of samples<br>* Whenever possible serum samples will be collected from all subjects to determine serum raxibacumab concentrations pre-infusion, and at specific timepoints post-infusion. In the event cerebrospinal fluid (CSF), pleural, ascites, or bronchoalveolar lavage (BAL) fluid are collected for ad hoc clinical laboratory testing, any remaining excess sample will be provided to Sponsor for determination of raxibacumab concentrations. Any available serum remaining from ad hoc clinical laboratory specimen collections prior to raxibacumab administration will be provided to Sponsor for measurement of serum PA concentrations. In addition, remaining post raxibacumab dose serum specimens may also be analyzed for TNA or ADA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of clinical benefit by overall survival for cohort 1 | Overall survival of subjects treated with raxibacumab for established inhalation anthrax or systemic. | Up to Week 24 | 
| Assessment of clinical benefit by emergence rate of systemic anthrax infection for Cohort 2 | The emergence rate of systemic anthrax infection to week 24 among subjects treated with raxibacumab for post exposure prophylaxis in Cohort 2 will be summarized. | Up to Week 24 | 
| Assessment of clinical benefit by rate of resolution of edema and healing of lesion without emergence of systemic anthrax infection for cohort 3 | Rate of resolution will be assessed for subjects treated with raxibacumab for localized uncomplicated cutaneous infection (without systemic symptoms or toxemia). | Up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rate on Day 14 and Day 28 | Fourteen and 28-day survival rate will be estimated using Kaplan-Meier technique. | Up to Day 28 | 
| Length of (Intensive Care Unit) ICU stay | These continuous endpoints will be summarized in mean, standard deviation, median, minimum, maximum and 95% CI | Up to Week 24 | 
| Incidence of associated complication of anthrax (meningitis, pleural effusion) | These categorical endpoints will be summarized in frequency and percentages | Up to Day 28 | 
| Incidence of the progression of the disease clinical stage for subject in Cohort 1 | The incidence of resolution or worsening of clinical symptoms will be summarized. Resolution of symptoms defined as subject demonstrates stabilization or improvement of clinical symptoms based on clinical findings and worsening of symptoms defined as subject demonstrates worsening of symptoms such that the staging moves from a lower stage to a higher stage. | Up to Week 24 | 
| Incidence of the progression to systemic anthrax infection for subjects in Cohorts 2 and 3 | The progression to systemic anthrax infection will be summarized using Kaplan-Meier technique. | Up to Week 24 | 
| Summary of the area of wound/lesions for subjects in Cohort 3 | The area of wound/lesions will be summarized by visits in mean, standard deviation and confidence interval (if appropriate). | Up to Week 24 | 
| Summary of significant concurrent medical treatment | Significant concurrent medical treatment will be summarised in terms of antibiotics, anthrax vaccine absorbed (AVA), corticosteroids and vasopressors. | Up to Week 24 | 
| Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs will be summarized by frequency and proportion of total subjects, system organ class and preferred term. Separate summaries will be produced for all AEs, treatment-related AEs and SAEs. | Up to Week 24 | 
| Summary of ECG data | ECG data and findings (and change from baseline) will be summarized by visit. | Up to Week 24 | 
| Summary of Vital Signs | Vital signs (temperature, heart rate, systolic and diastolic blood pressure, respiration rate, oxygen saturation) will be summarized by visit. Concomitant medications, medical and anthrax history and clinical signs and symptoms of anthrax will be presented in listings. | Up to Week 24 | 
| Summary of serum raxibacumab concentrations | Serum raxibacumab concentrations will be determined by an ECL-based immunoassay. Pharmacokinetic data including Cmax, AUC and t 1/2 will be presented in graphical and/or tabular form and will be summarized descriptively. | Up to Week 24 | 
| Summary of disease markers: Protective Antigen (PA), toxin neutralizing antibody (TNA) and Anti-drug antibody (ADA) levels | If adequate specimen remains after raxibacumab analysis is complete, specimens may also be analyzed for PA concentrations, TNA titers, and presence of anti-raxibacumab antibodies. The results for these endpoints will be descriptively and/or graphically summarized as appropriate to the data. | Up to Week 24 | 
| Length of hospital stay | These continuous endpoints will be summarized in mean, standard deviation, median, minimum, maximum and 95% CI | Up to Week 24 | 
| Summary of neurological function as assessed by Glasgow Coma Scale or Adelaide Pediatric Scale | These continuous endpoints will be summarized in mean, standard deviation, median, minimum, maximum and 95% CI | Up to 24 weeks | 
| Summary of daily functionality as assessed by Katz ADL | These continuous endpoints will be summarized in mean, standard deviation, median, minimum, maximum and 95% CI | Up to 24 weeks | 
| Incidence of bacteremia | These categorical endpoints will be summarized in frequency and percentages | Up to 24 weeks | 
| Summary of clinical chemistry and hematology laboratory data | Chemistry and hematology laboratory data (absolute values and change from baseline) will be summarized by visit. The frequency of laboratory abnormalities will be tabulated. Laboratory values will be assessed for significant changes from baseline. | Up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Raxibacumab, anthrax, anti-toxin