Brepocitinib for Uveitis

(CLARITY Trial)

Recruiting at 38 trial locations

Overseen By Clinical Trial Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Priovant Therapeutics, Inc.

Disqualifiers: Lymphoproliferative disorder, active malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests brepocitinib, a medication for individuals with active, non-infectious uveitis, an inflammation inside the eye. Researchers aim to determine if brepocitinib is safe and effective for this type of eye inflammation. Participants will receive either brepocitinib or a placebo (a harmless pill resembling the real medicine) to compare results. Individuals with ongoing uveitis in at least one eye, without an infection, might be suitable candidates. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

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.

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

Research has shown that brepocitinib has been tested in people with non-infectious uveitis, yielding positive results. In earlier studies, patients generally tolerated brepocitinib well. Some studies demonstrated significant improvements, with fewer treatment failures, indicating that the medication is effective and generally safe.

It's important to understand that this research is ongoing. The current trial phase indicates that brepocitinib has already passed initial safety tests. However, like any medication, side effects can occur, and individuals may react differently. Those considering joining a trial should discuss potential risks with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for uveitis?

Brepocitinib is unique because it targets the Janus kinase (JAK) and tyrosine kinase 2 (TYK2) pathways, which are involved in the inflammatory process of uveitis. Most current treatments for uveitis rely on corticosteroids or immunosuppressive agents that often come with significant side effects and long-term health risks. Brepocitinib's dual mechanism offers a more targeted approach, potentially reducing inflammation with fewer side effects. Researchers are excited about Brepocitinib because it could offer a more effective and safer alternative to existing therapies, improving the quality of life for patients with uveitis.

What evidence suggests that brepocitinib might be an effective treatment for uveitis?

Research has shown that brepocitinib might help treat non-infectious uveitis (NIU), which is inflammation inside the eye. In earlier studies, patients with active NIU experienced fewer treatment failures when using brepocitinib, particularly by week 24. Fewer participants saw their condition worsen during the study. The FDA has fast-tracked brepocitinib, indicating it could be a promising treatment option. Overall, these findings suggest that brepocitinib could effectively manage NIU symptoms. Participants in this trial will receive either brepocitinib or a placebo to further evaluate its effectiveness. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Brepocitinib

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

Citations

1. clinicaltrialsarena.com clinicaltrialsarena.com/analyst-comment/aao-2024-brepocitinib-neptune/

AAO 2024: Brepocitinib achieves treatment failure ... Brepocitinib showcased that active NIU patients had clinically meaningful treatment failure reductions in a dose-dependent manner by week 24.

2. clinicaltrialsarena.com clinicaltrialsarena.com/news/priovant-mulls-broad-autoimmune-indications-for-brepocitnib/

Priovant mulls broad autoimmune indications for brepocitinib Last month, the US Food and Drug Administration (FDA) granted a fast track designation to brepocitinib as a treatment for non-infectious uveitis ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06431373

NCT06431373 | A Study of Brepocitinib in Adults With ... The purpose of this study is to determine the safety and efficacy of brepocitinib in participants with active, non-anterior (intermediate, posterior, or pan) ...

4. clinicaltrials.eu clinicaltrials.eu/inn/brepocitinib-tosilate/

Brepocitinib Tosilate – Application in Therapy and Current ... This article explores a Phase 3 clinical trial investigating the efficacy and safety of Brepocitinib Tosilate, a new drug for treating dermatomyositis in adults ...

5. ophthalmologytimes.com ophthalmologytimes.com/view/roivant-announces-positive-neptune-study-results-for-brepocitinib-in-non-infectious-uveitis

Roivant announces positive NEPTUNE study results for ... Roivant and Priovant Therapeutics this week announced positive results from the Phase 2 NEPTUNE study (NCT05523765) evaluating brepocitinib ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05523765

A Study of Brepocitinib in Adults With Active Non-Infectious ... This study will evaluate the clinical safety and efficacy of oral brepocitinib in participants with active intermediate, posterior, or pan non-infectious ...

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/roivant-non-infectious-uveitis-trial/

Roivant, Priovant report positive data from non-infectious ... Roivant and Priovant have announced positive outcomes from the Phase II trial of brepocitinib in non-anterior non-infectious uveitis (NIU).