A Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab in Pediatric Patients Hospitalized with COVID-19

Phase 1

• Conditions: Coronavirus disease 2019 (COVID-19); Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2021-005332-27-FR
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-02-17
• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

- Aged less than 18 years at the time of signing Informed Consent Form or Assent (if applicable)
- Ability to comply with the study protocol, in the investigator's judgment
- Hospitalized with COVID-19 confirmed per a positive polymerase chain reaction (PCR) of any specimen and evidenced by chest X-ray or CT scan
- Receiving systemic corticosteroids at baseline
- Oxygen saturation <93% on room air, or requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) to maintain oxygen saturation >92% at screening and baseline
- For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agree to refrain from donating eggs during the treatment period and for 90 days after the final dose of TCZ
- For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, during the treatment period and for 60 days after the final dose of TCZ to avoid exposing the embryo
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

- Gestational age <37 weeks
- Known severe allergic reactions to TCZ or other monoclonal antibodies
- Active tuberculosis infection
- Uncontrolled active bacterial, fungal, viral, or other infection (besides COVID-19)
- Diagnosis or suspected diagnosis of multisystem inflammatory syndrome in children (MIS-C)
- In the opinion of the investigator, progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatments
- Have received oral anti-rejection or immunomodulatory drugs (including TCZ) within the past 3 months prior to enrollment
- Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) >10 x upper limit of normal (ULN) detected within 24 hours of screening
Platelet count <50,000/µL at screening
- Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 90 days after the final dose of TCZ
- Treatment with an investigational drug within 5 drug-elimination half-lives or 30 days, whichever is longer, of enrollment (except for anti-SARS-CoV-2 antibodies or directly acting antivirals)
- Participating in another interventional drug clinical trial (except for anti-SARS-CoV-2 antibodies or directly acting antivirals)
- Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To characterize the pharmacokinetics of tocilizumab (TCZ) through Day 28;Secondary Objective: - To characterize the pharmacodynamics of TCZ through Day 60<br>- To evaluate the safety of TCZ through Day 60<br>;Primary end point(s): 1. Serum concentrations of TCZ at specified timepoints and derived PK parameters (maximal serum concentration [Cmax], area under the concentration-time curve up to Day 28 [AUCDays 0-28], serum concentration on Day 28 [CDay28], total clearance of drug [CL], and volume of distribution);Timepoint(s) of evaluation of this end point: 1. Up to Day 28

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Duration of 90% saturation of soluble interleukin-6 receptor (sIL-6R) through Day 28<br>2. Concentrations of interleukin 6 (IL-6), sIL-6R, and C-reactive protein (CRP) at specified timepoints<br>3. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 grading scale<br>4. Incidence of serious adverse events<br>5. Change from baseline in targeted vital signs<br>6. Change from baseline in targeted clinical laboratory test results;Timepoint(s) of evaluation of this end point: 1. Up to Day 28<br>2. Up to Day 60<br>3-4. Up to approximately Day 60<br>5-6. Baseline (Day 1) to Day 60<br>