Baricitinib for Cardiac Sarcoidosis

Overseen By Angie Aberia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must be taking: Steroid-sparing therapy

Must not be taking: Biologic DMARDs, JAK inhibitors

Disqualifiers: VTE history, Smoking, Renal disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you are not currently taking any immunosuppressive medications other than specific steroid-sparing medications or prednisone at a low dose. If you are on other immunosuppressive drugs, you may need to stop them at least 28 days before screening.

What data supports the effectiveness of the drug Baricitinib for treating cardiac sarcoidosis?

Baricitinib has shown effectiveness in treating other inflammatory conditions like rheumatoid arthritis and systemic lupus erythematosus by reducing disease activity. It has also been effective in a case of giant-cell arteritis, suggesting its potential in managing inflammation-related diseases. ^{1 2 3 4 5}

What is the safety profile of Baricitinib in humans?

Baricitinib has been studied for safety in conditions like rheumatoid arthritis and COVID-19. Common side effects include infections like herpes zoster (shingles) and serious infections, but these generally reflect the risks of the diseases being treated. Major cardiovascular events and other serious side effects were within expected ranges for these conditions, and no major safety concerns were noted in hospitalized COVID-19 patients. ^{6 7 8 9 10}

How does the drug Baricitinib differ from other treatments for cardiac sarcoidosis?

Baricitinib is unique because it is a Janus kinase (JAK) inhibitor, which means it works by blocking specific enzymes involved in inflammation. This mechanism is different from other treatments for cardiac sarcoidosis, which may not target these enzymes directly. ^{11 12 13 14 15}

What is the purpose of this trial?

The goal of this clinical trial is to learn if baricitinib in combination with a background steroid-sparing medication can treat active cardiac sarcoidosis in adults. The main question it aims to answer is: - In patients with active cardiac sarcoidosis, does treatment with baricitinib improve cardiac sarcoidosis disease activity as assessed by changes on cardiac FDG-PET/CT? Participants will: * Take baricitinib in combination with a steroid-sparing therapy for up to 16 weeks * Visit the clinic every two to four weeks for checkups and tests * Be asked to complete questionnaires to see how they feel on baricitinib and medication diaries to record when they take baricitinib

Research Team

Matthew C Baker, MD, MS

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults with active cardiac sarcoidosis, a condition affecting the heart. Participants must be willing to take baricitinib alongside another medication that reduces the need for steroids and commit to regular clinic visits every 2-4 weeks.

Inclusion Criteria

I have been diagnosed with heart sarcoidosis through a PET-CT scan.

I have been diagnosed with cardiac sarcoidosis confirmed by biopsy and PET-CT scans.

I have been diagnosed with cardiac sarcoidosis confirmed by a specific heart scan.

Exclusion Criteria

Blood tests at screening meeting specific criteria for hemoglobin, neutrophils, absolute lymphocyte count, and platelets

Current smoking

I do not have a serious infection right now.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive baricitinib in combination with a steroid-sparing therapy for up to 16 weeks

16 weeks

Clinic visits every two to four weeks for checkups and tests

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Follow-up visits as needed

Treatment Details

Interventions

• Baricitinib

Trial Overview The study tests if baricitinib can improve symptoms of cardiac sarcoidosis when taken with steroid-sparing therapy. It measures changes in disease activity using FDG-PET/CT scans over a period of up to 16 weeks.

Participant Groups

Group I: baricitinib + steroid-sparing drug +/- glucocorticoid taper Experimental Treatment 1 Intervention

* Participants will be treated with baricitinib 4 mg daily for up to 16 weeks in combination with a background steroid sparing medication * Participants who are on steroids at the time of enrollment will continue the steroid at a dose of prednisone (or equivalent) ≤ 20mg PO daily at Baseline and complete an 8 week taper of their steroid medication per a standardized protocol

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Eli Lilly and Company

Industry 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

Baricitinib, an oral JAK1/JAK2 inhibitor, has a safety profile that reflects the inherent risks of the diseases it treats, with higher rates of infections and serious adverse events observed in patients with rheumatic diseases compared to those with dermatological conditions.

In clinical studies, the incidence of major adverse cardiovascular events (MACE) with baricitinib was lower than that seen with tofacitinib and comparable to tumor necrosis factor inhibitors, indicating a favorable safety profile, especially in hospitalized COVID-19 patients treated for up to 14 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19. Bieber, T., Feist, E., Irvine, AD., et al.[2023]

Baricitinib, an oral JAK1/JAK2 inhibitor, demonstrated an acceptable safety profile in 514 Japanese patients with rheumatoid arthritis over a median exposure of 1.7 years, with no deaths reported and manageable adverse events.

The most notable safety concern was an increased incidence of herpes zoster, although overall safety was comparable to that of RA patients in a broader integrated database, indicating that baricitinib is an effective treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment: An integrated analysis of Phases 2 and 3 trials. Harigai, M., Takeuchi, T., Smolen, JS., et al.[2021]

In a two-year study of 44 patients with rheumatoid arthritis, both baricitinib and tofacitinib were found to be effective in reducing disease activity, with baricitinib showing slightly greater reductions in the DAS28 scale and pain levels over 12 months.

Both medications had similar safety profiles, with low rates of adverse reactions (10% for baricitinib and 12.5% for tofacitinib) and comparable treatment discontinuation rates due to loss of effectiveness, indicating they are both viable options for managing rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib and tofacitinib in patients with rheumatoid arthritis: results of regular clinical practice. González-Freire, L., Giménez-Candela, RM., Castro-Luaces, S., et al.[2021]

Acalabrutinib, a second-generation BTK inhibitor, has shown high overall response rates of 96% in treatment-naive and 93% in relapsed/refractory chronic lymphocytic leukemia (CLL) patients, indicating its efficacy as a treatment option.

The safety profile of acalabrutinib is generally favorable, with most adverse effects being mild to moderate (grade 1-2), and only limited severe toxicities reported, suggesting it may be a safer alternative to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib and its use in treatment of chronic lymphocytic leukemia. Khan, Y., O'Brien, S.[2019]

References

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

JAK Inhibitor Effectiveness in Giant-Cell Arteritis With Large-Vessel Involvement Assessed by 18F-FDG PET-CT. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy of Baricitinib in Patients with Refractory Adult-Onset Still's Disease. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy of Long-Term Treatment with Once-Daily Baricitinib 2 mg in Patients with Active Rheumatoid Arthritis: Post Hoc Analysis of Two 24-Week, Phase III, Randomized, Controlled Studies and One Long-Term Extension Study. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Does baricitinib reduce disease activity in patients with systemic lupus erythematosus? A systematic review and meta-analysis of randomized controlled trials. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Mixed results with baricitinib in biological-resistant adult-onset Still's disease and undifferentiated systemic autoinflammatory disease. [2021]

6. England pubmed.ncbi.nlm.nih.gov

A real-world disproportionality analysis of FDA Adverse Event Reporting System (FAERS) events for baricitinib. [2021]

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

A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment: An integrated analysis of Phases 2 and 3 trials. [2021]

9. Spain pubmed.ncbi.nlm.nih.gov

Baricitinib and tofacitinib in patients with rheumatoid arthritis: results of regular clinical practice. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Safety of baricitinib in East Asian patients with moderate-to-severe active rheumatoid arthritis: An integrated analysis from clinical trials. [2021]

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

Asymptomatic profound sinus bradycardia (heart rate ≤45) in non-small cell lung cancer patients treated with crizotinib. [2022]

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

Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib. [2019]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Case report: Indolent drug-related pneumonitis with alectinib therapy in the treatment of non-small cell lung cancer. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Acalabrutinib and its use in treatment of chronic lymphocytic leukemia. [2019]

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

Phase II open label study of the oral vascular endothelial growth factor-receptor inhibitor PTK787/ZK222584 (vatalanib) in adult patients with refractory or relapsed diffuse large B-cell lymphoma. [2021]