BT-011 Pharmacokinetics of Botulism Antitoxin Heptavalent in Pediatric Patients

Study Description

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Brief Summary:

The purpose of this study is to verify the pediatric dosing recommendations for BAT® in pediatric patients that are treated with BAT® due to a confirmed or suspected case of botulism. One 5 mL blood sample will be obtained within 24 hours post BAT® administration. Study BT-011 will be run concurrently with the BAT patient registry (BT-010).

Condition or disease	Intervention/treatment	Phase
Botulism	Biological: One 5 mL of blood will be collected.	Phase 4

Detailed Description:

Objectives: The purpose of this study is to collect one serum sample from pediatric patients in order to analyze the pharmacokinetics of BAT® to verify the currently approved pediatric dosing recommendations.

Protocol Design: This is a single arm, multi-site Pharmacokinetics study in pediatric patients treated with BAT®. The study begins once participation in the study is confirmed by the physician and informed consent/assent is obtained from the patient and/or guardian. Concurrent participation in the BAT patient registry (BT-010) by the treating physician/facility is encouraged to collect safety and clinical outcome data.

Assessments: One 5 mL of blood collected to yield 2 mL serum sample will be collected post-BAT® administration. The blood sample should be collected no later than 24 hours post BAT® administration. To ensure sufficient detectable circulating levels of BAT® for pharmacokinetic analysis the target window of time for collection should be between 6 and 24 hours post-BAT® administration.

Pharmacokinetic or Efficacy Parameters: The BAT® serum concentration(s) obtained will be modeled using a population pharmacokinetic approach based on a previously developed model for BAT® in healthy adult human subjects for toxin serotypes A-G.

Individual Bayesian Pharmacokinetics parameters (i.e. clearance (CL), volume of distribution (Vc), volume of distribution of the central and the peripheral compartments (Vp)) and corresponding exposure metrics will be derived from the population analysis.

Primary Endpoints: The primary endpoint is the dosage level at which pharmacokinetic equivalence is reached i.e. the dosage at which BAT® is most effective against the symptoms of botulism. Following the estimation of exposure in pediatric patients, and similar to what was done for adult subjects, the margin of efficacy for 90% survival will be estimated in order to verify the appropriateness of the administered pediatric dose.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	3 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Pharmacokinetics of Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) - (Equine) (BAT™) in Pediatric Patients With a Confirmed or Suspected Exposure to Botulinum Toxin.
Actual Study Start Date :	October 2014
Actual Primary Completion Date :	July 2017
Actual Study Completion Date :	July 2017

Arms and Interventions

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Arm

Intervention/treatment

Experimental: One 5 mL blood sample will be collected; A single 5 mL blood sample will be collected from pediatric patients treated with BAT®. The blood sample should be collected no later than 24 hours post BAT® administration. To ensure sufficient detectable circulating levels of BAT® for pharmacokinetic analysis the target window of time for collection should be between 6 and 24 hours post-BAT® administration.

Biological: One 5 mL of blood will be collected.; The blood sample should be collected no later than 24 hours post BAT® administration. To ensure sufficient detectable circulating levels of BAT® for pharmacokinetic analysis the target window of time for collection should be between 6 and 24 hours post-BAT® administration.

Outcome Measures

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Primary Outcome Measures :

1. Area Under the Concentration-Time Curve (AUC 0-24h) [ Time Frame: 24 hours ]

   One 5 mL of blood collected to yield 2 mL serum sample will be collected post-BAT® administration.

   The blood sample should be collected no later than 24 hours post BAT® administration. To ensure sufficient detectable circulating levels of BAT® for Pharmacokinetic analysis the target window of time for collection should be between 6 and 24 hours post-BAT® administration.

   The BAT® serum concentration(s) obtained will be modeled using a population pharmacokinetic approach based on a previously developed model for BAT® in healthy adult human subjects for toxin serotypes A-G.

Eligibility Criteria

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Ages Eligible for Study:	up to 16 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Informed consent/assent (as applicable) is required for provision of a serum sample to Cangene.
• Pediatric patients [age category: pediatric—preterm and term newborn infants (0 to 27 days), infants and toddlers (28 days to 23 months), children (2 to 11-years), and adolescents (12 to 16-years)]
• Confirmed or suspected exposure to botulinum toxin.
• Treatment with BAT® deployed from the Strategic National Stockpile or state stockpiles.

Exclusion Criteria:

• If a blood sample cannot be collected from the pediatric subject within 24 hours of BAT® administration then the subject is excluded from the study.
• The 5 mL blood sample volume is deemed to be unsafe based on patient weight.

Contacts and Locations

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Sponsors and Collaborators

Cangene Corporation

Investigators

Study Chair:	Jason S Richardson, PhD	Clinical Research Scientist for Cangene Corporation (doing business as Emergent Biosolutions)
Study Chair:	Matt Cromie, MSc	Clinical Research Senior Manager for Cangene Corporation (doing business as Emergent Biosolutions)
Study Chair:	Christine Hall, PhD	Director Clinical Research for Cangene Corporation (doing business as Emergent Biosolutions)

More Information

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Additional Information:

Center for Disease Control and Prevention. Investigational heptavalent botulinum antitoxin to replace licensed botulinum antitoxin AB and investigational botulinum antitoxin E. Morbidity and Mortality Weekly Report. 2010;59(10):299. 

Guidance for industry and FDA staff. Best practices for conducting and reporting pharmacoepidemiologic safety studies using electronic health care data sets (draft guidance). United States Department of Health and Human 

BAT United States Prescribing Information, 03/201. 

Publications:

Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Hauer J, Layton M, Lillibridge S, Osterholm MT, O'Toole T, Parker G, Perl TM, Russell PK, Swerdlow DL, Tonat K; Working Group on Civilian Biodefense. Botulinum toxin as a biological weapon: medical and public health management. JAMA. 2001 Feb 28;285(8):1059-70. Review. Erratum in: JAMA 2001 Apr 25;285(16):2081.

Gangarosa EJ, Donadio JA, Armstrong RW, Meyer KF, Brachman PS, Dowell VR. Botulism in the United States, 1899-1969. Am J Epidemiol. 1971 Feb;93(2):93-101.

Lack JA, Stuart-Taylor ME. Calculation of drug dosage and body surface area of children. Br J Anaesth. 1997 May;78(5):601-5. Erratum in: Br J Anaesth 1997 Aug;79(2):268.

Shapiro RL, Hatheway C, Swerdlow DL. Botulism in the United States: a clinical and epidemiologic review. Ann Intern Med. 1998 Aug 1;129(3):221-8. Review.

Responsible Party:	Cangene Corporation
ClinicalTrials.gov Identifier:	NCT02051062 History of Changes
Other Study ID Numbers:	BT-011
First Posted:	January 31, 2014
Last Update Posted:	January 26, 2018
Last Verified:	January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Cangene Corporation:

Pharmacokinetics; BAT; Pediatric

Additional relevant MeSH terms:

Botulism; Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Neuromuscular Junction Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurotoxicity Syndromes	Foodborne Diseases; Poisoning; Chemically-Induced Disorders; Antitoxins; Botulinum Antitoxin; Immunologic Factors; Physiological Effects of Drugs