Brepocitinib for Uveitis

(NEPTUNE Trial)

No longer recruiting at 22 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an oral medication called brepocitinib to determine its safety and effectiveness for treating certain types of non-infectious uveitis, an inflammation inside the eye. The study targets individuals with active intermediate, posterior, or pan uveitis, where inflammation affects specific eye parts. Participants should currently use one non-corticosteroid, non-biologic treatment and must not have isolated anterior uveitis or any infectious uveitis. The trial involves taking one of two different daily doses of brepocitinib. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that brepocitinib is generally well-tolerated by patients. Earlier studies found significant improvements by week 24 for those taking brepocitinib, indicating effective treatment without major side effects. Brepocitinib targets specific enzymes (JAK1 and TYK2) involved in inflammation. Although detailed safety information from these studies isn't available, brepocitinib's advancement to this trial stage suggests it is safe enough for further testing. Participants can remain hopeful, as brepocitinib has shown promise in earlier research. ^{1 2 3 4 5}

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

Unlike the standard treatments for uveitis, such as corticosteroids or immunosuppressants, Brepocitinib offers a new approach by targeting specific pathways linked to inflammation. Brepocitinib is a dual inhibitor, which means it blocks both the tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1) pathways, crucial in the inflammatory process. This dual action could potentially offer more effective control of inflammation with fewer side effects than current options. Researchers are excited about Brepocitinib because it represents a promising alternative that might provide improved outcomes for patients with uveitis.

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

Research shows that brepocitinib might help treat non-infectious uveitis (NIU), an eye condition. In this trial, participants will receive either Brepocitinib Dose Level 1 or Dose Level 2. Previous studies have shown that patients with active NIU experienced fewer treatment failures after 24 weeks, with greater improvement observed at higher doses. While these results are encouraging, more research is needed to confirm them. These early findings suggest brepocitinib could be a helpful option for people with NIU. ^{2 3 6 7 8}

Who Is on the Research Team?

Brendan Johnson, PhD

Principal Investigator

SVP, Early Development

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Brepocitinib Dose Level 2 by mouth (PO) once daily (QD) Experimental Treatment 1 Intervention

Group II: Brepocitinib Dose Level 1 by mouth (PO) once daily (QD) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Priovant Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

570+

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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 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]

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. 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) ...

3. 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 ...

4. synapse.patsnap.com synapse.patsnap.com/drug/a9008e10ca084f3db9d6315c6458d6f9

Brepocitinib - Drug Targets, Indications, Patents Priovant is running a phase 3 trial in noninfectious uveitis and a midphase study in cutaneous sarcoidosis. The biotech began the phase 3 trial one year ago.

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05523765?term=brepocitinib&

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- ...

7. medchemexpress.com medchemexpress.com/PF-06700841_P-Tosylate.html?srsltid=AfmBOopvbxOeNmfG2yB4Gn10XZUlVkeSB_vqc8YB2kSB-Mb5IgJsi1bw

Brepocitinib P-Tosylate (Synonyms: PF-06700841 P- ... Brepocitinib (PF-06700841) P-Tosylate is a potent dual Janus kinase 1 (JAK1) and TYK2 inhibitor with IC50s of 17 nM and 23 nM, respectively.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12141190/

Pharmacotherapy for non-infectious uveitis: spotlight on phase ... We report on design, outcome measures, and key effectiveness and safety results of these trials. We also describe selected phase III clinical trials that ...