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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well abrocitinib, a daily pill, can treat moderate to severe cutaneous sarcoidosis, a condition causing skin issues due to clusters of inflammatory cells. The research aims to determine if this medication can reduce skin involvement and improve symptoms. Suitable candidates have noticeable skin problems from sarcoidosis that affect daily activities, such as obstructing vision or the nasal passage. Participants should be prepared to continue their current sarcoidosis medications and attend regular clinic visits. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that abrocitinib is likely to be safe for humans?

Research shows that abrocitinib is generally safe. Studies with this treatment have produced good results with few side effects. Although specific safety information for using abrocitinib to treat sarcoidosis is not yet available, it is currently being tested in a Phase 2 trial. Some safety information exists because the drug has already passed earlier safety-focused trials.

The FDA has approved abrocitinib for other conditions, indicating a well-understood safety profile. This approval can offer some reassurance about its safety. However, individual experiences may vary, so discussing potential risks with a healthcare provider is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Abrocitinib is unique because it targets the Janus kinase (JAK) pathway, offering a new approach to treating sarcoidosis. Unlike standard treatments, which often involve corticosteroids or immunosuppressants, abrocitinib specifically inhibits JAK1, which plays a crucial role in immune response regulation. This targeted action potentially reduces inflammation with fewer side effects, making it a promising option for patients who struggle with the side effects of current therapies. Researchers are excited about abrocitinib due to its potential for improved safety and efficacy in managing sarcoidosis symptoms.

What evidence suggests that abrocitinib might be an effective treatment for sarcoidosis?

Research has shown that Janus kinase (JAK) inhibitors, such as abrocitinib, may help reduce inflammation in conditions like sarcoidosis. One study found that a similar JAK inhibitor, tofacitinib, enabled 60% of patients with lung sarcoidosis to reduce their steroid use without worsening symptoms. Abrocitinib, which participants in this trial will receive, showed promise in a case where it was used with low-dose steroids for skin sarcoidosis, leading to significant improvement. These findings suggest that abrocitinib might also effectively treat moderate to severe skin sarcoidosis by addressing the underlying inflammation. ^{1 2 3 6 7}

Who Is on the Research Team?

William Damsky, M.D.

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05696795

NCT05696795 | Janus Kinase Inhibition in Sarcoidosis The primary outcome will be the percent change in the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) after 6 months of abrocitinib 200 mg ...

2. withpower.com withpower.com/trial/phase-2-sarcoidosis-1-2023-cfce7

Abrocitinib for Sarcoidosis · Info for Participants Another study found that Tofacitinib helped 60% of patients with lung sarcoidosis reduce their steroid use without worsening symptoms. These findings suggest ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12505053/

Systematic review and meta-analysis of the efficacy of biologic ... Data from two RCTs and two single-arm trials suggest that infliximab is efficacious in pulmonary sarcoidosis, with less support for cutaneous ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/09546634.2025.2556487

Abrocitinib combined with low-dose corticosteroids in the ... Abrocitinib combined with low-dose corticosteroids in the management of tattoo-related cutaneous sarcoidosis: a case report · Full Article · Figures & data ...

5. sigma.larvol.com sigma.larvol.com/product.php?e1=22884&tab=newstrac

Cibinqo (abrocitinib) News The patient showed significant clinical improvement following the combination therapy, with no observed treatment-related adverse events. This case suggests ...

6. ichgcp.net ichgcp.net/clinical-trials-registry/NCT05696795

Abrocitinib 200 mg in Sarcoidosis - Clinical Trials Registry The primary objective of this study is to determine whether oral abrocitinib reduces the CSAMI (a cutaneous sarcoid clinical scoring tool) in ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9014825/

Once-Daily Abrocitinib for the Treatment of Moderate-to- ... The positive results were obtained even starting from the first stages of the oral drug administration. The low frequency of side effects and ...