Brepocitinib for Uveitis

(NEPTUNE Trial)

Recruiting at 21 trial locations

Overseen By Clinical Trial Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Priovant Therapeutics, Inc.

Must be taking: Immunomodulatory therapy

Disqualifiers: Anterior uveitis, Active 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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

26 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial allows participants to be on one non-corticosteroid, non-biologic, immunomodulatory therapy, so you may need to adjust your current medications to meet this requirement.

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

Research shows that other drugs like tofacitinib and certolizumab pegol have been effective in treating uveitis, suggesting that similar treatments targeting inflammation might also be beneficial for this condition. ^{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 is a type of drug that blocks specific enzymes 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}

What is the purpose of this trial?

This trial will test the safety and effectiveness of a pill called brepocitinib in people with a type of eye inflammation that isn't caused by an infection. The pill works by calming the immune system to reduce swelling and irritation in the eye.

Research Team

Brendan Johnson, PhD

Principal Investigator

SVP, Early Development

Eligibility Criteria

Adults aged 18-74 with active non-infectious uveitis (intermediate, posterior, or panuveitis) can join. They must have certain levels of eye inflammation and may be on one non-corticosteroid treatment. Weight over 40 kg and BMI under 40 are required. Those with isolated anterior uveitis, recent cancers except some skin or localized cancers, high thrombosis risk, active infections, or herpes zoster risk cannot participate.

Inclusion Criteria

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

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

I have active inflammation in my eye, confirmed by a doctor.

Exclusion Criteria

I have inflammation in the front part of my eye.

I am at high risk for shingles reactivation.

I have a history of cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral brepocitinib for the treatment of non-infectious uveitis

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Brepocitinib

Trial Overview The trial is testing the safety and effectiveness of an oral medication called Brepocitinib for adults with specific types of eye inflammation known as intermediate, posterior, or panuveitis that isn't caused by an infection.

Participant Groups

Group I: Brepocitinib Dose Level 2 PO QD Experimental Treatment 1 Intervention

Group II: Brepocitinib Dose Level 1 PO QD Experimental Treatment 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]

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]

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]

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

Mycophenolate mofetil for the treatment of uveitis. [2022]

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

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

8. Brazil pubmed.ncbi.nlm.nih.gov

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

9. 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]