BT-011 Pharmacokinetics of Botulism Antitoxin Heptavalent in Pediatric Patients

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 Neurotoxin

The purpose of this study is to verify the pediatric dosing recommendations for BAT product in pediatric patients that are treated with BAT product due to a confirmed or suspected case of botulism. A minimum of one serum sample should be collected but whenever feasible additional serum samples (up to three per enrolled participant) may be collected from the participant or obtained from surplus standard of care samples, if available, within 32 hours after BAT product administration. Safety of the BAT product will also be evaluated. Emergent will follow-up with the physician by telephone after 30 days post-BAT product administration to collect AEs, SAEs, and unanticipated events.

Study Overview

• Status: Enrolling by invitation
• Conditions: Botulism
• Intervention / Treatment: Biological: Blood sample collection

Detailed Description

Primary Objective: To collect blood from pediatric participants to analyze the pharmacokinetics (PK) of BAT product to verify the current US FDA-approved pediatric dosing recommendations for BAT product.

Safety Objective: To evaluate the safety of BAT product in pediatric participants.

Protocol Design: This is a single arm, multi-site PK study in pediatric patients treated with BAT product.

Pharmacokinetic Parameters: The serum concentrations of BAT product obtained will be modeled using a population PK approach based on a previously developed model for BAT serotypes A through G in healthy adult human participants.

Safety Endpoints: The incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI) that occur within 30 days after BAT product administration. In this study hypersensitivity/allergic reactions including serum sickness, febrile reactions, and hemodynamic instability and bradycardia, as well as reports of an infectious disease transmission will be included as AESI.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Legally authorized representative is able and willing to voluntarily provide informed consent and patients to provide assent, if applicable.
2. Pediatric participants (age groups: birth to <two years, two to <six years, and six to <12 years).
3. Treatment with BAT product (initial dose only).
4. Blood sample can be collected (or standard of care sample scavenged) within 32 hours of completion of BAT product infusion.

Exclusion Criteria:

1. If the 5 mL blood sample volume is deemed, at the discretion of the investigator, to be unsafe based on patient weight or condition of health.
2. History of treatment with BabyBIG or other botulism antitoxin within the past 90 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blood sample collection; One to three 5 mL blood samples will be collected from pediatric participants treated with BAT product ideally 6-24 hours after administration, but within a maximum of 32 hours after administration.	Biological: Blood sample collection; One to three 5 mL blood samples will be collected from pediatric participants treated with BAT product ideally 6-24 hours after administration but within a maximum of 32 hours after administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Margin of PK Equivalence for 90% Survival	Margin of PK equivalence (MOE) for 90% survival relative to the healthy adult PK model, calculated to verify the appropriateness of administered pediatric dose. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window.	ideally up to 32 hours post-BAT product administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under Concentration Curve From Time 0 to Last Measurable Concentration [AUC0-t]	Pharmacokinetic Parameter: Estimated area under the serum concentration-time curve from time 0 to the last measurable serotype A concentration [AUC0-t]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window.	ideally up to 32 hours post-BAT product administration
Area Under Concentration Curve From Time 0 to Infinity [AUC0-inf]	Pharmacokinetic Parameter: Estimated area under the serum concentration-time curve from time 0 to infinity [AUC0-inf]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window.	ideally up to 32 hours post-BAT product administration
Between Subject Variability [BSV]	Pharmacokinetic Parameter: Between subject variability [BSV]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window.	ideally up to 32 hours post-BAT product administration
Maximum Serum Serotype A Concentration [Cmax]	Pharmacokinetic Parameters: Estimated maximum serum serotype A concentration [Cmax]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window.	ideally up to 32 hours post-BAT product administration
Systemic Clearance [CL]	Pharmacokinetic Parameters: Estimated systemic clearance [CL]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window.	ideally up to 32 hours post-BAT product administration
Intercompartmental Clearance [CLd]	Pharmacokinetic Parameters: Estimated intercompartmental clearance [CLd]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window.	ideally up to 32 hours post-BAT product administration
Central Volume of Distribution [Vc]	Pharmacokinetic Parameters: Estimated central volume of distribution [Vc]. All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window.	ideally up to 32 hours post-BAT product administration
Peripheral Volume of Distribution [Vp]	Pharmacokinetic Parameters: Estimated peripheral volume of distribution [Vp]). All collected samples of sufficient volume will be used provided both the BAT dosing time and sample collection time are known, even if outside the 32 hour collection window.	ideally up to 32 hours post-BAT product administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: AEs	Number of AEs that occur within 30 days after BAT product administration	Day 1 to Day 30
Safety: SAEs	Number of SAEs that occur within 30 days after BAT product administration	Day 1 to Day 30
Safety: AESI	Number of AESI that occur within 30 days after BAT product administration	Day 1 to Day 30

Collaborators and Investigators

• Sponsor: Emergent BioSolutions
• Investigators: Study Director: Bojan Drobic, PhD, Emergent BioSolutions Inc

Publications and helpful links

General Publications

• Richardson JS, Parrera GS, Astacio H, Sahota H, Anderson DM, Hall C, Babinchak T. Safety and Clinical Outcomes of an Equine-derived Heptavalent Botulinum Antitoxin Treatment for Confirmed or Suspected Botulism in the United States. Clin Infect Dis. 2020 Apr 15;70(9):1950-1957. doi: 10.1093/cid/ciz515.
• Parrera GS, Astacio H, Tunga P, Anderson DM, Hall CL, Richardson JS. Use of Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine) (BAT(R)) in Clinical Study Subjects and Patients: A 15-Year Systematic Safety Review. Toxins (Basel). 2021 Dec 27;14(1):19. doi: 10.3390/toxins14010019.
• Beliveau M, Anderson D, Barker D, Kodihalli S, Simard E, Hall C, Richardson JS. Exposure-Response Modeling and Simulation to Support Human Dosing of Botulism Antitoxin Heptavalent Product. Clin Pharmacol Ther. 2022 Jul;112(1):171-180. doi: 10.1002/cpt.2620. Epub 2022 May 16.
• Rao AK, Sobel J, Chatham-Stephens K, Luquez C. Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021. MMWR Recomm Rep. 2021 May 7;70(2):1-30. doi: 10.15585/mmwr.rr7002a1.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: January 29, 2014
• First Submitted That Met QC Criteria: January 29, 2014
• First Posted (Estimated): January 31, 2014

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Pediatric; Pharmacokinetics; BAT
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Infections; Neuromuscular Diseases; Foodborne Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Neuromuscular Junction Diseases; Clostridium Infections; Poisoning; Neurotoxicity Syndromes; Botulism
• Other Study ID Numbers: BT-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No