E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To characterize the pharmacokinetics (PK) of baricitinib in pediatric patients with COVID-19 |
|
E.2.2 | Secondary objectives of the trial |
- To describe the safety of baricitinib in pediatric patients with COVID-19
- To describe the effect of baricitinib on COVID-19 progression in pediatric patients
- To describe clinical outcomes in pediatric patients with COVID-19 treated with baricitinib |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patients from 1 to <18 years of age at the time of enrollment
- Hospitalized with coronavirus (SARS-CoV-2) infection, confirmed by NAAT or immunodiagnostic tests, with a positive result in a sample collected no more than 14 days prior to treatment assignment
- Require supplmental oxygen and have chest imaging findings to confirm respiratory disease due to COVID-19 within 72 hours of study entry and enrollment |
|
E.4 | Principal exclusion criteria |
- Are receiving biologic treatments (such as TNF inhibitors, interleukin inhibitors, T-cell or B-cell targeted therapies, interferons, or JAK inhibitors) for any indication at study entry; or are receiving other immunosuppressants such that, in the opinion of the investigator, participating in the study would put the participant at an unacceptable risk of immunosuppression. Note: A washout period is required prior to screening.
- Are receiving strong inhibitors of OAT3 (such as probenecid) that cannot be discontinued at study entry.
- Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening tests required)
- Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product
- Have received any live vaccine within 4 weeks before screening, or intend to receive a live vaccine during the study. Note: use of nonlive (inactivated) vaccinations is allowed for all participants
- Require invasive mechanical ventilation, including extracorporeal membrane oxygenation (ECMO) at study entry
- Current diagnosis of active malignancy that, in the opinion of the investigator, could constitute a risk when taking investigational product
- Have any history of venous thromboembolism (VTE) (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]) or are considered at high risk of VTE (DVT/PE) by the investigator
- Anticipated discharge from the hospital, or transfer to another hospital (or another unit), which is not a study site within 72 hours after study entry
- Have neutropenia (absolute neutrophil count < 1000 cells/microliters)
- Have lymphopenia (absolute lymphocyte count < 200 cells/microliters)
- Have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times AAULN
- Estimated glomerular filtration rate (eGFR) <40 milliliter/minute/1.73 meters squared |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic parameters, including AUC and Cmax of baricitinib, in pediatric patients with COVID-19 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Safety assessments, including AEs and laboratory abnormalities
2. Proportion of patients who require noninvasive ventilation/high-flow oxygen or invasive mechanical ventilation (including ECMO) by Day 28
3. Proportion of patients who die or require noninvasive ventilation/high-flow oxygen or invasive mechanical ventilation (including ECMO) by Day 28
4. Proportion of patients with at least 1-point improvement on NIAID-OS or live discharge from hospital at Day 4, Day 7, Day 10, Day 14, and Day 28
5. Number of ventilator-free days (Day 1 to Day 28)
6. Time to recovery on the NIAID-OS (Day 1 to Day 28)
7. Overall improvement on the NIAID-OS evaluated at Day 4, Day 7, Day 10, Day 14, and Day 28
8. Duration of hospitalization (Day 1 to Day 28)
9. All-cause mortality (Day 1 to Day 28 and Day 60)
10. Duration of stay in the intensive care unit (ICU) in days (Day 1 to Day 28) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary endpoints will be evaluated (Day 1 to Day 28), except: endpoint number 9 (Day 1 to Day 28 and Day 60) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Mexico |
United States |
Belgium |
Italy |
Netherlands |
Spain |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |