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Non-infectious inflammatory eye disease, such as uveitis and scleritis, is a chronic, auto-immune process that leads to vision loss. While steroids are effective in the short term, the side-effect profile of chronic steroid use necessitates the identification of effective steroid-sparing therapies. Tofacitinib is a small molecule that inhibits the signaling pathways of multiple inflammatory cytokines. The investigators plan to evaluate whether tofacitinib may have efficacy for patients with uveitis and / or scleritis.
This study is a prospective, single-site, open-label investigation of tofacitinib for refractory uveitis. The study will be for 24 weeks, with potential 1-year extension for treatment responders. The patients will self-administer the medication.
Eligible patients would be those patients with a diagnosis of uveitis who meet the following criteria:
For patients naive to oral steroid-sparing therapy (e.g., methotrexate, azathioprine, or mycophenolate), tofacitinib will be initiated as monotherapy. For patients who have failed or had only a partial response to oral steroid-sparing therapy, tofacitinib will be initiated as an add-on therapy. For patients intolerant to a conventional agent, tofacitinib will be initiated as replacement monotherapy. For patients who have failed biologic therapy (e.g. adalimumab), biologic therapy will be discontinued and tofacitinib will be initiated as replacement therapy without change to concurrent conventional steroid-sparing agents. Study visits will occur at baseline/enrollment, and weeks 4, 8, 12, 16, & 24 (+/- 2 weeks). Clinic visits may occur more frequently as determined by the treating physician. Laboratory monitoring (Table 1) will be obtained according to standard of care for drug toxicity monitoring. Clinical responses will be evaluated at 24 weeks, with the primary outcome defined as treatment failure.
All patients will undergo a predetermined oral steroid taper starting at 60mg of prednisone (or equivalent) and tapering over 14 weeks (Table 2). All patients will undergo a predetermined topical steroid drop taper starting at their current dose (Table 3).
Patients will have an ophthalmological evaluation by their treating ophthalmologist at Washington University. Steroid sparing therapy will be managed by rheumatologists or uveitis specialists at Washington University. All patients will be evaluated for an associated systemic rheumatologic condition.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tofacitinib Treatment | Experimental | 11mg extended-release tofacitinib, once daily, oral |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tofacitinib | Drug | tofacitinib extended release, 11mg, daily, oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Treatment Failure (Composite Outcome) | new inflammatory lesions relative to baseline OR 2-step increase in anterior chamber cell or vitreous haze OR worsening of visual acuity by two or more rows on ETDRS chart | 180 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lynn M Hassman, MD PhD | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University in Saint Louis | St Louis | Missouri | 63110 | United States |
Active uveitis despite at least 10mg prednisone for 2 weeks.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tofacitinib Treatment | tofacitinib: tofacitinib extended release, 11mg, daily, oral |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tofacitinib | single arm- tofacitinib 11mg daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Treatment Failure (Composite Outcome) | new inflammatory lesions relative to baseline OR 2-step increase in anterior chamber cell or vitreous haze OR worsening of visual acuity by two or more rows on ETDRS chart | Posted | Count of Participants | Participants | 180 days |
|
|
18 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tofacitinib Treatment | tofacitinib: tofacitinib extended release, 11mg, daily, oral |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| cutaneous melanoma | Skin and subcutaneous tissue disorders | Non-systematic Assessment | right upper extremity melanoma, with negative sentinel lymph nodes |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lynn Hassman, Assistant Professor and Study PI | Washington University in St. Louis | 3142730341 | lhassman@wustl.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 1, 2020 | Jan 7, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D014605 | Uveitis |
| D015423 | Scleritis |
| ID | Term |
|---|---|
| D014603 | Uveal Diseases |
| D005128 | Eye Diseases |
| D015422 | Scleral Diseases |
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| ID | Term |
|---|---|
| C479163 | tofacitinib |
| C014289 | 5-(tetradecyloxy)-2-furancarboxylic acid |
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| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| 0 |
| 5 |
| 2 |
| 5 |
| 0 |
| 5 |
|
| squamous cell carcinoma | Skin and subcutaneous tissue disorders | Non-systematic Assessment | squamous cell carcinoma on arm, fast-growing, history of multiple squamous cell carcinomas removed |
|
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