Baricitinib for Pediatric COVID-19

(COV-BARRIER Trial)

Recruiting at 30 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Biologics, Immunosuppressants, OAT3 inhibitors

Disqualifiers: Active TB, Active malignancy, VTE history, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose for this study is to determine if the study drug baricitinib is effective and safe in hospitalized pediatric participants with Coronavirus disease 2019 (COVID -19) and to confirm the dose.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. If you are on biologic treatments, strong inhibitors of OAT3, or other immunosuppressants, you might need to discontinue them, as a washout period (time without taking certain medications) is required before screening.

How is the drug Baricitinib unique for treating pediatric COVID-19?

Baricitinib is unique for treating pediatric COVID-19 because it is an oral medication that works by inhibiting specific enzymes (called Janus kinases) involved in inflammation, which may help reduce the severe inflammatory response seen in COVID-19. This mechanism of action is different from other treatments that primarily target the virus itself. ^{1 2 3 4 5}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for hospitalized children aged 1 to <18 with COVID-19 who need supplemental oxygen but are not on invasive ventilation or ECMO. They should have confirmed respiratory disease from COVID-19 and be stable enough not to require hospital transfer within 72 hours. Children with severe liver issues, poor kidney function, known drug allergies, high risk of blood clots, certain infections or immunosuppression conditions are excluded.

Inclusion Criteria

I need extra oxygen and have lung issues from COVID-19 confirmed by a recent scan.

I am hospitalized with COVID-19.

I am under 18 years old.

Exclusion Criteria

I have had blood clots in my veins or am at high risk for them.

I have active TB or untreated latent TB.

My kidney function is low, with an eGFR below 40.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Baricitinib given orally to participants daily

4 weeks

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Baricitinib

Trial Overview The study tests the effectiveness and safety of Baricitinib in pediatric patients hospitalized with COVID-19. It aims to confirm the appropriate dosage for treating these young patients effectively without causing harm.

Participant Groups

Group I: Baricitinib Experimental Treatment 1 Intervention

Baricitinib given orally to participants daily

Baricitinib is already approved in United States, European Union for the following indications:

Approved in United States as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Approved in European Union as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

Crizotinib has been approved by the FDA for treating pediatric patients aged 1 year and older with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL), marking the first approval for this condition in children.

In a trial involving 26 patients aged 1-20 years, crizotinib demonstrated a high efficacy with an objective response rate of 88%, indicating its potential as an effective treatment option for this rare type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA approval summary: Crizotinib for pediatric and young adult patients with relapsed or refractory systemic anaplastic large cell lymphoma. Merino, M., Kasamon, Y., Li, H., et al.[2022]

Ceritinib, at a recommended dose of 500 mg/m2 once daily, demonstrated promising antitumor activity in pediatric patients with ALK-positive malignancies, particularly in inflammatory myofibroblastic tumors (IMT) and anaplastic large cell lymphoma (ALCL), as well as in some cases of neuroblastoma.

The safety profile of ceritinib was manageable, with 81% of patients experiencing grade 3 or 4 adverse events, primarily increases in liver enzymes, indicating that while the treatment can have serious side effects, it is consistent with what has been observed in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study. Fischer, M., Moreno, L., Ziegler, DS., et al.[2022]

The FDA approved the combination of dabrafenib and trametinib for treating pediatric patients with low-grade glioma (LGG) with a BRAFV600E mutation, marking the first systemic therapy approved for this condition.

In a clinical trial with 110 patients, the combination therapy showed a significantly higher overall response rate of 47% compared to 11% for the standard treatment of carboplatin and vincristine, along with longer progression-free survival of 20.1 months versus 7.4 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Dabrafenib in combination with trametinib for BRAF V600E mutation-positive low-grade glioma. Barbato, MI., Nashed, J., Bradford, D., et al.[2023]

Children and adolescents with Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) have shown promising results with a combination of intensive chemotherapy and the targeted drug imatinib, achieving an 88% 3-year event-free survival rate in a small trial.

The addition of tyrosine kinase inhibitors (TKIs) like imatinib to chemotherapy may become the preferred treatment for Ph(+) ALL, and this approach could potentially be adapted for other ALL subtypes to enhance efficacy while reducing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Philadelphia chromosome-positive acute lymphoblastic leukemia in children: new and emerging treatment options. Schultz, KR., Prestidge, T., Camitta, B.[2022]

The maximum-tolerated dose (MTD) of cediranib in children with recurrent CNS tumors was initially set at 32 mg/m²/day, but excessive toxicities led to concerns about its long-term tolerability.

At a lower dose of 20 mg/m²/day, cediranib still showed poor tolerability, indicating that both doses may not be suitable for extended treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors. Kieran, MW., Chi, S., Goldman, S., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

FDA approval summary: Crizotinib for pediatric and young adult patients with relapsed or refractory systemic anaplastic large cell lymphoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Dabrafenib in combination with trametinib for BRAF V600E mutation-positive low-grade glioma. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Philadelphia chromosome-positive acute lymphoblastic leukemia in children: new and emerging treatment options. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors. [2018]