Abrocitinib for Sarcoidosis

Overseen By Yvette Strong

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must be taking: Methotrexate, Prednisone

Must not be taking: Immunosuppressants, CYP2C19 inhibitors

Disqualifiers: HIV, Hepatitis, Malignancy, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new pill called abrocitinib for patients with moderate to severe skin sarcoidosis. The pill aims to reduce inflammation by targeting a specific protein in the immune system. Researchers hope this will improve skin lesions better than current treatments.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify that you must stop all current medications. However, you must be on a stable dose of any systemic therapies for sarcoidosis for at least 3 months, with no plans to change them in the next 6 months. You can continue taking low-dose prednisone (up to 20 mg daily) or methotrexate (up to 15 mg weekly). There is a 2-week washout period for topical medications.

Will I have to stop taking my current medications?

You may need to stop some medications, but you can continue taking low-dose prednisone (up to 20 mg daily) or methotrexate (up to 15 mg weekly). There is a 2-week washout period for topical medications, but most oral medications cannot be stopped.

What data supports the idea that Abrocitinib for Sarcoidosis is an effective drug?

The available research does not provide specific data on Abrocitinib for Sarcoidosis. However, studies on a similar drug, Tofacitinib, which also targets the same pathway, show promising results. In one study, 10 patients with skin sarcoidosis treated with Tofacitinib showed improvement, with 6 experiencing complete recovery. Another study found that Tofacitinib helped 60% of patients with lung sarcoidosis reduce their steroid use without worsening symptoms. These findings suggest that drugs targeting the same pathway as Abrocitinib could be effective for Sarcoidosis, but more research is needed specifically on Abrocitinib. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Abrocitinib for treating sarcoidosis?

Research on a similar drug, tofacitinib, which also targets the JAK-STAT pathway, shows improvement in sarcoidosis symptoms, suggesting that Abrocitinib might have similar effects. ^{1 2 3 4 5}

What safety data is available for Abrocitinib in treating sarcoidosis?

The provided research does not contain specific safety data for Abrocitinib (also known as Cibinqo or PF-04965842) in the treatment of sarcoidosis. The studies mentioned focus on other treatments like infliximab, TNF antagonists, and tofacitinib for sarcoidosis, but do not provide safety information on Abrocitinib. ^{1 2 3 6 7}

Is the drug Abrocitinib a promising treatment for sarcoidosis?

Abrocitinib, like other drugs in its class, may be promising for sarcoidosis because similar drugs have shown potential in reducing symptoms and helping patients reduce their reliance on steroids. ^{1 2 3 4 8}

How does the drug Abrocitinib differ from other treatments for sarcoidosis?

Abrocitinib is a Janus kinase (JAK) inhibitor, which is a novel approach for treating sarcoidosis by targeting specific immune pathways involved in the disease. Unlike traditional treatments like glucocorticoids, which have broad effects, JAK inhibitors like Abrocitinib specifically suppress certain immune responses, potentially reducing side effects and improving outcomes. ^{1 2 3 4 8}

Research Team

William Damsky, M.D.

Principal Investigator

Yale University

Eligibility Criteria

Adults with moderate to severe cutaneous sarcoidosis, confirmed by skin biopsy, can join this trial. They must have been on stable medication doses for 3 months if using other treatments and agree to not change these during the study. Women who can get pregnant need a negative pregnancy test and must use birth control. People with certain infections, liver or kidney issues, clotting disorders, cancer (except certain skin cancers), or taking strong drug inhibitors are excluded.

Inclusion Criteria

I am willing to undergo skin biopsies, blood tests, and full body photos for the study.

I am able to become pregnant and agree to use birth control and have a negative pregnancy test before starting the medication.

My skin condition is severe and affects many areas, needing systemic treatment.

Exclusion Criteria

My skin condition's severity score is 10 or less.

I have a history of blood clots, including in my veins or lungs.

Platelets <150,000/mm3

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abrocitinib 200 mg daily for 6 months to assess its effectiveness in treating moderate to severe cutaneous sarcoidosis

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of molecular signatures and adverse events

4 weeks

Treatment Details

Interventions

• Abrocitinib

Trial Overview The trial is testing abrocitinib 200 mg daily as an oral treatment for patients with moderate to severe cutaneous sarcoidosis. The goal is to see how effective it is in reducing symptoms of the disease when taken once every day.

Participant Groups

Group I: Abrocitinib 200 mg daily Experimental Treatment 1 Intervention

6 months of treatment with abrocitinib 200 mg daily

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

Approved in European Union as Cibinqo for:

• Moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy

Approved in United States as Cibinqo for:

• Refractory, moderate-to-severe atopic dermatitis in patients 12 years of age and older whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Tofacitinib, a JAK inhibitor, led to significant clinical improvement in a patient with long-standing multiorgan sarcoidosis who did not respond to other treatments, showing remission of skin lesions and resolution of internal organ lesions after 6 months.

The treatment resulted in the resolution of granulomatous inflammation and normalization of disease biomarkers, highlighting the potential of JAK inhibition as a new therapeutic approach for difficult-to-treat sarcoidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Multiorgan Sarcoidosis With Tofacitinib. Damsky, W., Young, BD., Sloan, B., et al.[2020]

In an open-label trial involving 10 patients with cutaneous sarcoidosis, treatment with tofacitinib, a Janus kinase inhibitor, led to significant improvements in skin symptoms, with 6 patients achieving a complete response after 6 months.

Tofacitinib appears to improve sarcoidosis by inhibiting type 1 immune responses, particularly by suppressing the cytokine IFN-γ, which is linked to macrophage activation and the disease's pathogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis. Damsky, W., Wang, A., Kim, DJ., et al.[2023]

In a study of 132 patients with severe and refractory sarcoidosis, TNF antagonists showed a clinical response rate of 64%, particularly effective for symptoms involving the nervous system, heart, skin, and upper respiratory tract.

While TNF antagonists helped reduce the need for prednisone, they were associated with a high rate of adverse events (52%), including infections and allergic reactions, leading to treatment interruptions in 23% of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tumor necrosis factor antagonists in refractory sarcoidosis: A multicenter study of 132 patients. Jamilloux, Y., Cohen-Aubart, F., Chapelon-Abric, C., et al.[2018]

In a proof-of-concept study involving 5 patients with corticosteroid-dependent pulmonary sarcoidosis, 60% (3 out of 5) were able to reduce their corticosteroid dosage by at least 50% after 16 weeks of treatment with tofacitinib, a Janus kinase inhibitor.

The patients who successfully tapered their corticosteroids also experienced improved respiratory symptoms and stable lung function, suggesting that JAK-inhibitors could be a promising alternative therapy for managing pulmonary sarcoidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib as a Steroid-Sparing Therapy in Pulmonary Sarcoidosis, an Open-Label Prospective Proof-of-Concept Study. Friedman, MA., Le, B., Stevens, J., et al.[2021]

Monoclonal antibody therapies, particularly anti-TNF-α and anti-JAK-STAT inhibitors, show promise as effective treatments for refractory cutaneous sarcoidosis, with 15 out of 16 studies reporting partial to complete resolution of skin lesions within 2 weeks to 18 months.

While anti-TNF-α therapies were associated with more adverse events, including two deaths, anti-JAK-STAT therapies reported no adverse events, highlighting the need for further studies to establish safety and efficacy before these treatments can be standardized for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Clinical Studies on the Effects of Tumor Necrosis Factor-Alpha (TNF-α) and Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) Antibody Therapies in Refractory Cutaneous Sarcoidosis: A Systematic Review. Toriola, SL., Satnarine, T., Zohara, Z., et al.[2023]

In a study of 28 patients with chronic steroid-resistant sarcoidosis treated with infliximab over a period from 2003 to 2010, 88% of patients benefited from long-term treatment, showing significant clinical improvement, especially in those with extrapulmonary disease.

The treatment was found to be safe, with only one patient (6%) experiencing adverse effects that required temporary withdrawal, indicating a favorable safety profile for long-term infliximab use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term treatment with infliximab in patients with sarcoidosis. Hostettler, KE., Studler, U., Tamm, M., et al.[2015]

Sarcoidosis can present in various ways, with some patients experiencing spontaneous remission while others face severe, progressive disease that affects their survival and quality of life.

Four high-risk phenotypes of sarcoidosis—treatment-refractory pulmonary disease, cardiac sarcoidosis, neurosarcoidosis, and multiorgan sarcoidosis—have been identified as critical areas for research, highlighting the need for better understanding of their diagnosis, biomarkers, and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Presentation and Treatment of High-Risk Sarcoidosis. Perlman, DM., Sudheendra, MT., Furuya, Y., et al.[2022]

Refractory pulmonary sarcoidosis is defined by progressive disease despite at least 10 mg of prednisolone for three months, requiring additional treatments due to ineffectiveness or intolerability, and significant impairment of life due to symptoms.

For patients with refractory sarcoidosis, treatment options include second-line agents like methotrexate and infliximab, and newer anti-fibrotic drugs like pirfenidone may also be promising, with lung transplantation considered for those unresponsive to medical therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refractory pulmonary sarcoidosis - proposal of a definition and recommendations for the diagnostic and therapeutic approach. Korsten, P., Strohmayer, K., Baughman, RP., et al.[2020]

References

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

Treatment of Multiorgan Sarcoidosis With Tofacitinib. [2020]

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

Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis. [2023]

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

Efficacy and safety of tumor necrosis factor antagonists in refractory sarcoidosis: A multicenter study of 132 patients. [2018]

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

Tofacitinib as a Steroid-Sparing Therapy in Pulmonary Sarcoidosis, an Open-Label Prospective Proof-of-Concept Study. [2021]

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

Recent Clinical Studies on the Effects of Tumor Necrosis Factor-Alpha (TNF-α) and Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) Antibody Therapies in Refractory Cutaneous Sarcoidosis: A Systematic Review. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Long-term treatment with infliximab in patients with sarcoidosis. [2015]

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

Clinical Presentation and Treatment of High-Risk Sarcoidosis. [2022]

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

Refractory pulmonary sarcoidosis - proposal of a definition and recommendations for the diagnostic and therapeutic approach. [2020]