An Interventional Study of Upadacitinib Extended-Release Tablets in Patients With Refractory Uveitis

Phase 4Active Not RecruitingNCT07773623

Tianjin Medical University30 enrolled

Overview

Upadacitinib sustained-release tablets have not yet been approved for the treatment of uveitis. The current use falls under the category of "off-label medication", which means providing patients with potentially beneficial treatment options in the absence of formal approval. Based on existing case reports and mechanism studies, we believe that upadacitinib sustained-release tablets have potential therapeutic value for patients with uveitis who have not responded well to traditional treatment regimens or those who have not responded well to traditional treatment combined with biologics (adalimumab). Therefore, we plan to conduct this clinical study to systematically evaluate its efficacy and safety in patients with refractory uveitis and explore better treatment options for these patients.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Uveitis

Interventions

Eligibility

Sex: ALLMin age: 12 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 1.Patients voluntarily participate in the study and sign the informed consent form. 2.Male and female subjects aged 12 to 70 years (inclusive). 3.Patients with autoimmune uveitis who have been on long-term treatment with corticosteroids combined with immunosuppressants, with or without adalimumab, but have shown no remission or have had recurrent episodes. 4.Subjects (and their partners) agree to have no pregnancy plans during the entire trial period and within 1 month after the end of the study, and voluntarily take contraceptive measures. Exclusion Criteria: * 1.History or symptoms suggestive of demyelinating disease (including myelitis and optic neuritis) on neurological examination, including but not limited to optic neuritis. 2.Significant media opacities that interfere with visual acuity testing, anterior segment evaluation, or fundus examination, or inability to dilate the pupil adequately. 3.Monocular patients judged by the investigator to be unsuitable for enrollment. 4.Intravitreal antiVEGF (vascular endothelial growth factor) therapy (e.g., ranibizumab, aflibercept, or conbercept) within 90 days prior to baseline. 5.Ozurdex (dexamethasone implant) insertion within 6 months prior to baseline. 6.Intravitreal methotrexate injection within 90 days prior to baseline. 7.Subjects meeting any of the following criteria related to latent or active tuberculosis (TB) infection: 1. History of active TB within ≤ 3 years before screening (however, if \> 3 years and with documented evidence of adequate treatment, enrollment may be permitted); 2. Signs or symptoms suggestive of active TB during history taking and/or physical examination at screening; 3. Recent close contact with a person with active TB; 4. Positive T cell test for TB infection at screening. If the initial test result is indeterminate, the subject will be excluded from the study. For subjects who have already completed appropriate standard treatment for latent TB prior to screening and have no additional risk factors, imaging findings, or specific evidence supporting latent or active TB, exceptions to positive or indeterminate results may be considered, provided that the investigator consults with a qualified infectious disease specialist to assess the risk of TB (including extrapulmonary TB) and discusses with the sponsor. 8.Positive for hepatitis C antibody, or HIV antibody, or Treponema pallidum antibody at screening. 9.Presence of severe, progressive, or uncontrolled symptoms of renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiovascular, neurological, or cerebral disease. Subjects with malignancies, or any condition that, in the investigator's opinion, would place the patient at undue risk by participating in the study. 10.History of severe allergic or anaphylactic reactions to upadacitinib or any of its components

Outcomes

Primary Outcomes

Change from Baseline in Best-Corrected Visual Acuity (BCVA) at Month 3, 6, 12 and 24.

Best-corrected visual acuity (BCVA) will be recorded as ETDRS letter scores converted from Snellen charts. BCVA will be measured at baseline, Month 3, Month 6, Month 12 and Month 24. The change in letter score from baseline will be calculated at each time-point to evaluate the effect of upadacitinib on subjects' visual function.

Time frame: From enrollment to the end of treatment at 24 months

Change from Baseline in Anterior Chamber Cell Grade at Month 3, 6, 12 and 24

Anterior chamber cell grade will be assessed by slit-lamp biomicroscopy following the SUN standardized uveitis grading criteria. Assessments will be performed at baseline, Month 3, Month 6, Month 12 and Month 24. Grade changes relative to baseline will be computed at each visit for longitudinal analysis of anterior-segment intraocular inflammation over treatment.

Time frame: From enrollment to the end of treatment at 24 months

Change from Baseline in Vitreous Cell/Vitreous Haze Grade at Month 3, 6, 12 and 24.

Vitreous cell and vitreous haze will be graded by slit-lamp and indirect ophthalmoscopy using the Nussenblatt standardized scoring system. Evaluations will be conducted at baseline, Month 3, Month 6, Month 12 and Month 24. Grade changes versus baseline will be calculated at each time-point to assess the therapeutic response of vitreous inflammation to upadacitinib.

Time frame: 24 months from enrollment to treatment

Secondary Outcomes

The time for complete disappearance of all active inflammatory reactions in the eyes after treatment with upatiden sustained-release tablets

Complete resolution is defined as the absence of all active inflammatory signs in the eye, as determined by slit-lamp examination. This endpoint will be assessed at baseline, Month 3, Month 6, Month 12 and Month 24 . The time to resolution will be calculated from the date of first dose of upadacitinib to the date of the first documented absence of active inflammation

Time frame: From enrollment to the end of treatment at 24 months

Incidence of Adverse Events During 24-month Follow-up

All adverse events (including infection, haematological abnormalities, liver function abnormality, thrombosis, hypersensitivity reactions, etc.) will be documented across the 24-month study period. The count, category, severity and causal relationship to study drug will be summarized for adverse events and serious adverse events.

Time frame: From enrollment to the end of treatment at 24 months

Ocular complications after treatment with upatinib sustained-release tablets

Ocular complications will be evaluated using slit-lamp examination, optical coherence tomography (OCT), and fundus photography at baseline, Month 3, Month 6, and Month 12. The outcome will describe the occurrence, type, severity, and relationship to stud.

Time frame: From enrollment to the end of treatment at 24 months

The usage load of hormones and immunosuppressants after treatment with upatiden sustained-release tablets

This endpoint will assess the cumulative use burden of corticosteroids and immunosuppressants, including dose, duration, and/or frequency, as documented during follow-up visits at baseline, Month 3, Month 6, Month 12, and Month 24. The outcome will quantify the overall exposure to these concomitant medications over the 24-month treatment period.

Time frame: From enrollment to the end of treatment at 24 months

Occurrence of Uveitis Relapse or Exacerbation During 24-month Follow-up

Uveitis relapse/exacerbation events will be documented throughout the 24-month observation period. Relapse is defined as ≥2-grade increase in anterior-chamber cell grade, ≥2-grade increase in vitreous cell/haze grade, ≥3-line Snellen visual loss, new active retinal/choroidal lesions, new vascular leakage on fundus fluorescein angiography, or recurrent/worsening macular edema confirmed by OCT. Number, timing and frequency of relapses will be summarized.

Time frame: 24 months from enrollment to treatment

Change from Baseline in Complete Blood Count Parameters at Month 3, 6, 12 and 24.

Peripheral blood samples will be collected at baseline, Month 3, Month 6, Month 12 and Month 24 for complete blood count testing, including absolute neutrophil count (ANC, cells/mm³), lymphocyte count (cells/mm³), hemoglobin (g/dL) and platelet count (10⁹/L). Changes from baseline will be calculated for each parameter to evaluate the haematological effects of upadacitinib.

Time frame: 24 months from enrollment to treatment

Change from Baseline in Liver Enzyme Levels at Month 3, 6, 12 and 24

Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) will be measured at baseline, Month 3, Month 6, Month 12 and Month 24, expressed in U/L. Changes from baseline will be calculated at each time-point to monitor upadacitinib-associated liver function abnormalities.

Time frame: 24 months from enrollment to treatment

Change from Baseline in Lipid Profile Parameters at Month 3, 6, 12 and 24

Fasting lipid profiles, including total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), will be measured at baseline, Month 3, Month 6, Month 12 and Month 24, expressed in mmol/L. Changes from baseline will be calculated for each parameter to assess the effect of upadacitinib on lipid metabolism.

Time frame: 24 months from enrollment to treatment

An Interventional Study of Upadacitinib Extended-Release Tablets in Patients With Refractory Uveitis

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes