Brepocitinib for Uveitis

(CLARITY Trial)

Recruiting at 36 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Priovant Therapeutics, Inc.

Disqualifiers: Lymphoproliferative disorder, active malignancy, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the safety and efficacy of brepocitinib in participants with active, non-anterior (intermediate, posterior, or pan) non-infectious uveitis (NIU).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Brepocitinib for treating uveitis?

While there is no direct data on Brepocitinib for uveitis, similar treatments like tofacitinib and certolizumab pegol have shown success in treating uveitis, suggesting that Brepocitinib might also be effective. ^{1 2 3 4 5}

How is the drug Brepocitinib unique for treating uveitis?

Brepocitinib is unique because it is a janus kinase inhibitor (JAK-I), which targets specific pathways involved in inflammation, potentially offering a new approach for treating uveitis compared to traditional treatments like corticosteroids or other immunosuppressants. ^{2 6 7 8 9}

Eligibility Criteria

Adults aged 18-74 with active, non-infectious uveitis (intermediate, posterior, or panuveitis), not caused by an infection. Participants must have certain levels of eye inflammation or vitreous haze and weigh over 40 kg with a BMI under 40 kg/m2.

Inclusion Criteria

I have active inflammation in at least one of my eyes.

I weigh more than 40 kg and my BMI is less than 40.

I have been diagnosed with a type of eye inflammation that is not caused by an infection.

Exclusion Criteria

I have not had a blood clot or heart disease in the past year.

I currently have, or recently had, an infection.

I have or might have an eye infection causing inflammation.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral brepocitinib or placebo to assess safety and efficacy in treating non-infectious uveitis

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Brepocitinib (Corticosteroid)

Trial Overview The trial is testing the safety and effectiveness of Brepocitinib in reducing eye inflammation compared to a placebo. It also looks at whether Brepocitinib can help reduce the need for corticosteroids used to treat uveitis.

Participant Groups

Group I: Arm 1 Experimental Treatment 1 Intervention

Group II: Arm 2 Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Priovant Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

570+

Findings from Research

In a study of 7 patients with chronic-relapsing uveitis who had previously failed other treatments, 71.4% achieved quiescence after 10.4 months of treatment with certolizumab pegol (CZP).

Visual acuity improved significantly after 1 and 6 months of treatment, and no adverse events were reported, indicating that CZP is a safe and effective option for refractory uveitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Certolizumab Pegol, a New Anti-TNF-α in the Armamentarium against Ocular Inflammation. Llorenç, V., Mesquida, M., Sainz de la Maza, M., et al.[2022]

Tofacitinib was successfully used to treat two patients with refractory uveitis and scleritis, conditions that did not respond to multiple steroid-sparing therapies.

The treatment resulted in a durable resolution of both uveitis and scleritis, suggesting that tofacitinib could be a promising new option for managing severe inflammatory eye diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib for refractory uveitis and scleritis. Paley, MA., Karacal, H., Rao, PK., et al.[2022]

A 61-year-old woman experienced recurrent uveitis after starting treatment with the cancer drugs dabrafenib and pembrolizumab for metastatic melanoma, highlighting a potential safety concern with these therapies.

This case is notable as it documents the occurrence of acute uveitis in the same patient after sequential treatment with both a targeted therapy (dabrafenib) and an immune checkpoint inhibitor (pembrolizumab), suggesting a need for monitoring eye health in patients receiving these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of recurrent bilateral uveitis independently associated with dabrafenib and pembrolizumab therapy. Taylor, SC., Hrisomalos, F., Linette, GP., et al.[2022]

In a study of 21 patients with longstanding uveitis, treatment with golimumab (GOL) or certolizumab pegol (CZP) significantly reduced the frequency of ocular flares from 128.6 to 42.9 events per 100 patients-year, indicating their efficacy as treatment options.

Both GOL and CZP demonstrated good long-term retention rates (54.5% for CZP and 50.0% for GOL) and had an excellent safety profile, making them viable alternatives for patients who had previously not responded to other TNF-α blockers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of certolizumab pegol and golimumab in the treatment of non-infectious uveitis. Tosi, GM., Sota, J., Vitale, A., et al.[2019]

Tocilizumab (TCZ) demonstrated rapid and sustained improvement in ocular parameters for patients with refractory uveitis associated with Behçet's disease, with complete remission achieved in eight out of eleven patients studied.

While TCZ was effective for uveitis, it showed limited efficacy for extraocular manifestations of Behçet's disease, and two patients experienced severe side effects leading to treatment withdrawal, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behçet's disease: multicentre retrospective study. Atienza-Mateo, B., Calvo-Río, V., Beltrán, E., et al.[2018]

A 24-year-old female with refractory juvenile idiopathic arthritis-associated uveitis achieved clinical remission after switching to upadacitinib therapy, despite previous failures with tofacitinib.

This case indicates that changing between different Janus kinase inhibitors (JAK-Is) can be an effective strategy for treating JIAU when other treatments have not worked.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Effect of Upadacitinib in an Adult Patient with Juvenile Idiopathic Arthritis-associated Uveitis after Unsatisfactory Response to Tofacitinib: A Case Report. Baquet-Walscheid, K., Heinz, C., Rath, T., et al.[2023]

In a study of 100 patients with noninfectious uveitis, mycophenolate mofetil (MMF) demonstrated an 84.6% success rate in reducing prednisone dosage to 10 mg daily after one year, indicating its efficacy in managing inflammation.

MMF was generally well-tolerated, with a low discontinuation rate of 0.09 per patient-year due to side effects, primarily gastrointestinal issues, which aligns with findings from other studies on immunosuppressive treatments for ocular inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil for the treatment of uveitis. Teoh, SC., Hogan, AC., Dick, AD., et al.[2022]

A 54-year-old woman with melanoma developed VKH-like uveitis as a side effect of dabrafenib/trametinib therapy, highlighting a potential risk associated with these medications.

The intraocular inflammation resolved after stopping dabrafenib and using corticosteroids, emphasizing the importance of monitoring for uveitis in patients undergoing treatment with these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vogt-Kayanagi-Harada-Like Uveitis Induced by Dabrafenib/Trametinib Therapy for Cutaneous Malignant Melanoma. Kaymak, NZ., Kaplan, AT.[2023]

In a retrospective study of 16 patients with noninfectious uveitis treated with mycophenolate mofetil (MMF) for at least 6 months, 67% achieved a reduction in oral prednisone dosage to ≤10 mg/day after 1 year, and 83% after 2 years, indicating MMF's effectiveness in managing inflammation.

Complete or partial control of inflammation was achieved in 43.7% of patients after 1 year, with moderate tolerability noted, as adverse effects were relatively low, including gastrointestinal issues and infections at a rate of 0.03 patient-year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil as an immunomodulator in refractory noninfectious uveitis. Rodriguez, EE., Sakata, VM., Cavalcanti, DC., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Certolizumab Pegol, a New Anti-TNF-α in the Armamentarium against Ocular Inflammation. [2022]

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

Tofacitinib for refractory uveitis and scleritis. [2022]

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

A case of recurrent bilateral uveitis independently associated with dabrafenib and pembrolizumab therapy. [2022]

4. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and safety of certolizumab pegol and golimumab in the treatment of non-infectious uveitis. [2019]

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

Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behçet's disease: multicentre retrospective study. [2018]

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

Beneficial Effect of Upadacitinib in an Adult Patient with Juvenile Idiopathic Arthritis-associated Uveitis after Unsatisfactory Response to Tofacitinib: A Case Report. [2023]

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

Mycophenolate mofetil for the treatment of uveitis. [2022]

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

Vogt-Kayanagi-Harada-Like Uveitis Induced by Dabrafenib/Trametinib Therapy for Cutaneous Malignant Melanoma. [2023]

9. Brazil pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil as an immunomodulator in refractory noninfectious uveitis. [2022]