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An Open Label, Phase IV Study Evaluating the Clinical Benefit, Safety and Pharmacokinetics of Raxibacumab in Subjects Exposed to Bacillus Anthracis

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ClinicalTrials.gov Identifier: NCT02177721
Recruitment Status : Not yet recruiting
First Posted : June 30, 2014
Last Update Posted : November 27, 2017
Sponsor:
Collaborators:
Centers for Disease Control and Prevention
Department of Health and Human Services
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Infections, Bacterial Biological: Collection of samples Phase 4

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : September 28, 2018
Estimated Primary Completion Date : April 1, 2021
Estimated Study Completion Date : April 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anthrax
Drug Information available for: Raxibacumab

Arm Intervention/treatment
Experimental: Raxibacumab arm
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.
Biological: Collection of samples

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 GSK for determination of raxibacumab concentrations.

Any available serum remaining from ad hoc clinical laboratory specimen collections prior to raxibacumab administration will be provided to GSK for measurement of serum PA concentrations. In addition, remaining post raxibacumab dose serum specimens may also be analyzed for TNA or ADA. If serum, pleural fluid, ascitic fluid, CSF, and BAL sample volume remains following analyses by GSK, the remaining sample may be sent to CDC for investigational analyses. Any such analyses performed by CDC will be reported separately, by the CDC.





Primary Outcome Measures :
  1. Assessment of clinical benefit by overall survival for cohort 1 [ Time Frame: Up to Week 24 ]
    Overall survival of subjects treated with raxibacumab for established inhalation anthrax or systemic

  2. Assessment of clinical benefit by emergence rate of systemic anthrax infection for Cohort 2 [ Time Frame: Up to Week 24 ]
    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.

  3. Assessment of clinical benefit by rate of resolution of edema and healing of lesion without emergence of systemic anthrax infection for cohort 3 [ Time Frame: Up to Week 24 ]
    Rate of resolution will be assessed for subjects treated with raxibacumab for localized uncomplicated cutaneous infection (without systemic symptoms or toxemia).


Secondary Outcome Measures :
  1. Survival rate on Day 14 and Day 28 [ Time Frame: Up to Day 28 ]
    Fourteen and 28-day survival rate will be estimated using Kaplan-Meier technique.

  2. Length of (Intensive Care Unit) ICU stay [ Time Frame: Up to Week 24 ]
    These continuous endpoints will be summarized in mean, standard deviation, median, minimum, maximum and 95% CI

  3. Incidence of associated complication of anthrax (meningitis, pleural effusion) [ Time Frame: Up to Day 28 ]
    These categorical endpoints will be summarized in frequency and percentages

  4. Incidence of the progression of the disease clinical stage for subject in Cohort 1 [ Time Frame: Up to Week 24 ]
    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.

  5. Incidence of the progression to systemic anthrax infection for subjects in Cohorts 2 and 3 [ Time Frame: Up to Week 24 ]
    The progression to systemic anthrax infection will be summarized using Kaplan-Meier technique.

  6. Summary of the area of wound/lesions for subjects in Cohort 3 [ Time Frame: Up to Week 24 ]
    The area of wound/lesions will be summarized by visits in mean, standard deviation and confidence interval (if appropriate).

  7. Summary of significant concurrent medical treatment [ Time Frame: Up to Week 24 ]
    Significant concurrent medical treatment will be summarised in terms of antibiotics, anthrax vaccine absorbed (AVA), corticosteroids and vasopressors.

  8. Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 24 ]
    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.

  9. Summary of ECG data [ Time Frame: Up to Week 24 ]
    ECG data and findings (and change from baseline) will be summarized by visit.

  10. Summary of Vital Signs [ Time Frame: Up to Week 24 ]
    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.

  11. Summary of serum raxibacumab concentrations [ Time Frame: Up to Week 24 ]
    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.

  12. Summary of disease markers: Protective Antigen (PA), toxin neutralizing antibody (TNA) and Anti-drug antibody (ADA) levels [ Time Frame: Up to Week 24 ]
    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.

  13. Length of hospital stay [ Time Frame: Up to Week 24 ]
    These continuous endpoints will be summarized in mean, standard deviation, median, minimum, maximum and 95% CI

  14. Summary of neurological function as assessed by Glasgow Coma Scale or Adelaide Pediatric Scale [ Time Frame: Up to 24 weeks ]
    These continuous endpoints will be summarized in mean, standard deviation, median, minimum, maximum and 95% CI

  15. Summary of daily functionality as assessed by Katz ADL [ Time Frame: Up to 24 weeks ]
    These continuous endpoints will be summarized in mean, standard deviation, median, minimum, maximum and 95% CI

  16. Incidence of bacteremia [ Time Frame: Up to 24 weeks ]
    These categorical endpoints will be summarized in frequency and percentages

  17. Summary of clinical chemistry and hematology laboratory data [ Time Frame: Up to 24 weeks ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02177721


Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Sponsors and Collaborators
GlaxoSmithKline
Centers for Disease Control and Prevention
Department of Health and Human Services
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02177721     History of Changes
Other Study ID Numbers: 200137
First Posted: June 30, 2014    Key Record Dates
Last Update Posted: November 27, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
Raxibacumab
anthrax
anti-toxin

Additional relevant MeSH terms:
Bacterial Infections
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs