Baricitinib for Pediatric COVID-19

(COV-BARRIER Trial)

Recruiting at 29 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug baricitinib (also known as Olumiant) is safe and effective for treating hospitalized children with COVID-19. Taken as a pill, baricitinib may help alleviate breathing problems caused by the virus. The trial seeks participants who are currently hospitalized with COVID-19, require supplemental oxygen, and have confirmed lung issues from the virus. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that baricitinib is likely to be safe for pediatric COVID-19 patients?

Research shows that baricitinib is generally safe for children in the hospital with severe COVID-19. In earlier studies, most children handled the treatment well. Rarely, the treatment was stopped early due to unusual lab results.

Baricitinib is already approved for adults with COVID-19, indicating a well-understood safety profile. However, researchers are still learning about its effects on children, particularly how their bodies process the drug. Overall, current evidence suggests that baricitinib is well-tolerated, but careful monitoring remains important with any treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for COVID-19?

Baricitinib is unique because it targets the Janus kinase (JAK) pathway, which plays a key role in inflammation and immune response. Most treatments for pediatric COVID-19 focus on antiviral effects or symptom management, but baricitinib works differently by directly modulating the immune system to reduce inflammation. Researchers are excited about baricitinib's potential to offer a more targeted approach, potentially leading to faster and more effective relief for young patients battling severe COVID-19 symptoms.

What evidence suggests that baricitinib might be an effective treatment for pediatric COVID-19?

Research has shown that baricitinib may help treat COVID-19 in hospitalized patients. In adults, studies have found that adding baricitinib to regular care can shorten recovery time and improve health outcomes. Although less information exists about its use in children, early findings suggest that baricitinib is safe for children with severe COVID-19. It reduces inflammation, a major issue in severe COVID-19 cases. This approach has proven effective in adults and is being tested in this trial to determine if it can help children similarly. ^{1 2 4 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40204287/

Safety Data for Baricitinib Use in Children With Severe ... Conclusions: Baricitinib appears safe in children hospitalized for severe COVID-19. Most early baricitinib discontinuation for abnormal ...

2. fda.gov fda.gov/media/143823/download

Baricitinib EUA Fact Sheet for HCP There are limited clinical data available for baricitinib in pediatric patients 2 to less than 18 years of age hospitalized with COVID-19 requiring ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05074420?term=baricitinib&rank=8

A Study of Baricitinib (LY3009104) in Children With COVID ... The purpose for this study is to determine if the study drug baricitinib is effective and safe in hospitalized pediatric participants with Coronavirus disease ...

4. trials.lilly.com trials.lilly.com/en-US/trial/306960

A Study of Baricitinib (LY3009104) in Children With COVID-19 ... The purpose for this study is to determine if the study drug Baricitinib is effective and safe in hospitalized pediatric participants with Coronavirus disease ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04421027

NCT04421027 | A Study of Baricitinib (LY3009104) in ... The reason for this study is to see if the study drug baricitinib is effective in hospitalized participants with COVID-19. Official Title. A Randomized ...

6. publications.aap.org publications.aap.org/hospitalpediatrics/article-pdf/15/5/e203/1797153/hosppeds.2024008245.pdf

Safety Data for Baricitinib Use in Children With Severe ... The objective of this study is to describe the safety and outcomes following the use of baricitinib for children with severe COVID-19. METHODS. Setting, ...

7. olumiant.lilly.com olumiant.lilly.com/hcp/covid-19

About Olumiant® for use in COVID-19 A multicenter, adaptive, randomized blinded controlled trial of the safety and efficacy of investigational therapeutics for the treatment of Covid-19 in ...