Clinical trial NCT02051062: 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE4
Conditions: Botulism
Keywords: Pharmacokinetics
BAT
Pediatric
Lead sponsor: Emergent BioSolutions
Sponsor class: INDUSTRY
First posted: 2014-01-31
Enrollment: 10
Sex: ALL
Minimum age (years): 1
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Margin of PK Equivalence for 90% Survival
timeFrame: ideally up to 32 hours post-BAT product administration
Secondary outcomes:
measure: Area Under Concentration Curve From Time 0 to Last Measurable Concentration [AUC0-t]
timeFrame: ideally up to 32 hours post-BAT product administration
measure: Area Under Concentration Curve From Time 0 to Infinity [AUC0-inf]
timeFrame: ideally up to 32 hours post-BAT product administration
measure: Between Subject Variability [BSV]
timeFrame: ideally up to 32 hours post-BAT product administration
measure: Maximum Serum Serotype A Concentration [Cmax]
timeFrame: ideally up to 32 hours post-BAT product administration
measure: Systemic Clearance [CL]
timeFrame: ideally up to 32 hours post-BAT product administration
measure: Intercompartmental Clearance [CLd]
timeFrame: ideally up to 32 hours post-BAT product administration
measure: Central Volume of Distribution [Vc]
timeFrame: ideally up to 32 hours post-BAT product administration
measure: Peripheral Volume of Distribution [Vp]
timeFrame: ideally up to 32 hours post-BAT product administration
Other outcomes:
measure: Safety: AEs
timeFrame: Day 1 to Day 30
measure: Safety: SAEs
timeFrame: Day 1 to Day 30
measure: Safety: AESI
timeFrame: Day 1 to Day 30
Locations:
Study officials:
affiliation: Emergent BioSolutions
name: Clinical Development Representative
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.