BT-011 Pharmacokinetics of Botulism Antitoxin Heptavalent in Pediatric Patients

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 Neurotoxin

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• Margin of PK Equivalence for 90% Survival [Time frame: ideally up to 32 hours post-BAT product administration]

Secondary outcome measures (8)

• Area Under Concentration Curve From Time 0 to Last Measurable Concentration [AUC0-t] [Time frame: ideally up to 32 hours post-BAT product administration]
• Area Under Concentration Curve From Time 0 to Infinity [AUC0-inf] [Time frame: ideally up to 32 hours post-BAT product administration]
• Between Subject Variability [BSV] [Time frame: ideally up to 32 hours post-BAT product administration]
• Maximum Serum Serotype A Concentration [Cmax] [Time frame: ideally up to 32 hours post-BAT product administration]
• Systemic Clearance [CL] [Time frame: ideally up to 32 hours post-BAT product administration]
• Intercompartmental Clearance [CLd] [Time frame: ideally up to 32 hours post-BAT product administration]
• Central Volume of Distribution [Vc] [Time frame: ideally up to 32 hours post-BAT product administration]
• Peripheral Volume of Distribution [Vp] [Time frame: ideally up to 32 hours post-BAT product administration]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• 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.
• History of treatment with BabyBIG or other botulism antitoxin within the past 90 days.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

Center list to be confirmed — check the primary protocol.

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. PMID 31209461
• 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. PMID 35050996
• 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. PMID 35467014
• 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. PMID 33956777

Identifiers

NCT: NCT02051062 · BT-011

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗