Study of the Effectiveness of Ozurdex for the Control of Uveitis

Uveitis, Posterior Clinical Trial

Official title:

Proof of Concept Study of the Effectiveness of Ozurdex in Lieu of Oral Corticosteroids for the Control of Active Intermediate and Posterior Uveitis Requiring Immunosuppressive Drug Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02049476
• Other study ID #: NA_00088146
• Status: Completed
• Phase: Phase 4
• Start date: January 2014
• Est. completion date: June 30, 2018

Study information

• Verified date: June 2019
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate whether or not the dexamethasone pellet (Ozurdex®, Allergan, Irvine, CA) can replace oral corticosteroid (e.g. prednisone) in the treatment of active sight-threatening, noninfectious intermediate and/or posterior uveitis in which immunosuppressive drug therapy is indicated.

Uveitis is an inflammation inside the eye. Uveitis can decrease patients' vision if it is not treated.

The dexamethasone pellet is an implant filled with a corticosteroid medicine. This therapy is approved by the Food and Drug Administration (FDA) for the treatment of intermediate and/or posterior uveitis.

In this study investigators want to see if using the implant together with systemic immunosuppressive drug therapy can result in lower ocular side effect profile but is effective enough to replace the use of high-dose systemic corticosteroids in the treatment of active intermediate and/or posterior uveitis. Knowing the effectiveness and safety of these treatments is important because the kinds of uveitis being studied usually need to be treated for many years. This information may help researchers understand uveitis better and may suggest ways of improving treatment.

Adult patients with intermediate and/or posterior uveitis for which immunosuppressive drug therapy with high-dose corticosteroid is planned may join.

Description:

Objectives: This is a single arm study evaluating whether or not the dexamethasone pellet (Ozurdex®, Allergan, Irvine, CA) can replace oral corticosteroid (e.g. prednisone) in the treatment of active sight-threatening, noninfectious intermediate or posterior uveitis in which immunosuppressive drug therapy is indicated.

Background: Intermediate and posterior uveitis are thought to be severe intraocular inflammation that may lead to permanent visual loss. It is estimated that these forms of uveitis comprise the fifth or sixth leading cause of blindness and tend to affect working class age patients, thus causing loss of work hours and diminished productivity and quality of life. Because the posterior segment of the eye is not adequately treated by corticosteroid drops often systemic drug therapy is used including oral corticosteroids or prednisone. Prednisone can have a myriad of side effects in approximately one-quarter to one-third of cases treated in tertiary care centers such as ours, additional medications such as immunosuppressive drugs are required to control the disease and/or to allow for appropriate tapering of oral prednisone to subsequent levels that have a low side effect profile when delivered over a long period of time. Typically, chronic prednisone therapy in doses of 7.5 mg daily or less are thought to have a low enough side effect profile to be amenable to long-term therapy. However frequently immunosuppressive drugs are required to get the dosing to this level. There are occasions when patients are intolerant of any dose of oral corticosteroids or are intolerant of the higher doses of oral corticosteroids (30 - 60 mg daily) and therefore this treatment modality is avoided due to prednisone's attendant side effects. Although periocular and intravitreal corticosteroids injections may be performed, with these modalities the standard of care is to wait until the disease reactivates before instituting such therapy and therefore a chronic suppressive dose is not obtained. The fluocinolone acetonide implant (Retisert®, Bausch and Lomb, Tampa, FL) is FDA-approved for the treatment of intermediate and posterior uveitis and it is equally effective in controlling uveitis as high-dose oral corticosteroids but avoids the systemic side effects associated with the use of high doses of oral corticosteroids. However, this form of local therapy has high rates of ocular side effects, including ocular hypertension causing glaucoma and/or requiring glaucoma surgery and cataracts. Furthermore, every two and half to three years the implant is exhausted of corticosteroid and therefore repeat surgical insertion of another implant may be required. A useful potential therapy for the treatment of these patients would be a shorter-acting local corticosteroid that could be delivered in conjunction with systemic immunosuppressive drug therapy that would have a lower ocular side effect profile but still would be effective enough to replace the use of high-dose systemic corticosteroids in the treatment of active intermediate or posterior uveitis. It is possible that the dexamethasone pellet could fill this unique role in the treatment of uveitis. Investigators propose this study to evaluate dexamethasone pellet for this specific use among patients with active intermediate and posterior uveitis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 30, 2018
• Est. primary completion date: June 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Active sight-threatening intermediate or posterior uveitis for which immunosuppressive drug therapy is planned and the physician is considering treatment with high-dose corticosteroid to control the uveitis whilst immunosuppressive drugs are being instituted or adjusted. Note: it is acceptable for the patient to already be on an immunosuppressive drug as long as high dose corticosteroids are indicated.

• Patients must be age 18 years or older (the dexamethasone pellet is not FDA-approved for pediatric use) and sign an informed consent.

• The ocular media must be clear enough to obtain optical coherence photography (OCT) and fundus photographs.

• No elective intraocular surgery should be planned for the first 3 months after enrollment.

Exclusion Criteria:

• Infectious uveitis

• History of scleritis

• Active or suspected viral infection of the cornea or conjunctiva

• History of mycobacterial or fungal disease

• HIV positivity

• Age <18 years old

• Allergy to dexamethasone

• Uncontrolled intraocular pressure (IOP)

• Advanced glaucoma

• Aphakia with rupture of the posterior lens capsule

• Anterior chamber IntraOcualr Lens (ACIOL) with rupture of the posterior lens capsule

• Media opacity that would preclude evaluation of the posterior pole via fundus photography or OCT assessment

• Planned elective ocular surgery within 3 months of enrollment

• Any systemic disease requiring systemic corticosteroids.

Related Conditions & MeSH terms

• Uveitis
• Uveitis, Intermediate
• Uveitis, Posterior

Intervention

Drug:
• Dexamethasone pellet
Dexamethasone pellet placement occurs within 14 days of baseline examination; for patients with bilaterally active uveitis, placement of a dexamethasone pellet in the second eye should occur within 14 days of the first implantation or within 30 day of the baseline examination. Repeated placement is permitted every 3 months based on the best clinical judgment of the doctor and the study protocol.

Locations

Country	Name	City	State
United States	The Wilmer Eye Institute, Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Allergan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mean Intraocular Pressure (IOP)	Mean IOP (mmHg) was calculated at each visit	Baseline, 1 month, 3 months, 6 months, and 12 months visit
Other	Number of Eyes With a Need for Cataract Surgery	Number of eyes that had progression of cataract defined as any interval increase in nuclear, cortical or posterior sub capsular cataract from a previous visit that resulted in cataract surgery.	Baseline, 1 month, 3 months, 6 months, and 12 months visit
Primary	Number of Participants With Absence of Intraocular Inflammation at 6 Months	Absence of intraocular inflammation (e.g. less than trace anterior chamber (AC) cells; no vitreous haze; inactive chorioretinal lesions) is used to assess control of intraocular inflammation following treatment.	at 6-month visit
Secondary	Number of Participants With Absence of Intraocular Inflammation at 12 Months	Absence of intraocular inflammation (e.g. less than trace anterior chamber (AC) cells; no vitreous haze; inactive chorioretinal lesions) is used to assess control of intraocular inflammation following treatment.	12-month clinical visit