Clinical trial NCT02049476: Study of the Effectiveness of Ozurdex for the Control of Uveitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Uveitis, Intermediate
Uveitis, Posterior
Keywords: Uveitis, Intermediate
Uveitis, Posterior
Dexamethasone
Immunosuppressive Agents
Eye Abnormalities
Eye Diseases
Ophthalmology
Ophthalmologic Surgical Procedures
Vision Disorders
Inflammation
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2014-01-30
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Absence of Intraocular Inflammation at 6 Months
timeFrame: at 6-month visit
Secondary outcomes:
measure: Number of Participants With Absence of Intraocular Inflammation at 12 Months
timeFrame: 12-month clinical visit
Other outcomes:
measure: Mean Intraocular Pressure (IOP)
timeFrame: Baseline, 1 month, 3 months, 6 months, and 12 months visit
measure: Number of Eyes With a Need for Cataract Surgery
timeFrame: Baseline, 1 month, 3 months, 6 months, and 12 months visit
Locations:
city: Baltimore
country: United States
facility: The Wilmer Eye Institute, Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Department of Ophthalmology, Johns Hopkins School of Medicine,
name: Jennifer E Thorne, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: