Clinical trial NCT00790803: Pegaptanib Therapy in Non-Infectious Uveitic Cystoid Macular Edema
Official title: Vascular Endothelial Growth Factor (VEGF)Blockade With Intravitreal Pegaptnib in Non-Infectious Uveitic Cystoid Macular Edema (CME)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Uveitis
Cystoid Macular Edema
Keywords: uveitis
cystoid macular edema
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2008-11-14
Enrollment: 5
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: According to a recent estimate more than 280,000 people in the United States are affected by uveitis each year. This report, also estimated that uveitis is the reason for 30,000 new cases of blindness/year and up to 10 percent of all cases of blindness. The purpose of this trial is to determine the effectiveness of VEGF blockade with intravitreal pegaptanib in patients with uveitic CME.

Detailed description: 1. Cystoid macular edema is a common complication of uveitic intraocular inflammatory diseases and is characterized by intraretinal edema involving the outer plexiform layer. Intraocular inflammation or uveitis may be associated with non infectious or infectious etiologies. The early symptoms of CME include a decrease or blurry central vision. With long standing CME there is a substantial risk of photoreceptor degeneration and ensuing long term decrease in the quality and level of visual acuity (VA). Furthermore it has been shown that in patients with uveitis, the morphologic features of macular edema and macular thickness correlated with final VA. Current therapeutic interventions have had at best modest results in patients with CME who have had decreased VA. This may the case with systemic interventions also.
2. Vascular endothelial growth factor is a very strong inducer of blood vessel permeability and has been linked to the ocular manifestations of uveitis including CME by experienced researchers both in experimental and clinical settings. In animal tests, VEGF has been shown to be 50,000 times more potent than histamine, the molecule commonly associated with blood vessel leakage related to allergies. Also in animal tests, it has been shown that VEGF is required for the blood vessel permeability associated with neovascular AMD and diabetic retinopathy that have been shown to have an inflammatory component. In addition to its anti-angiogenic property of inhibiting abnormal blood vessel growth, pegaptanib has been shown in animal tests to inhibit blood vessels from leaking into the retina. Uveitis has been shown to be associated with ocular neovascularization both clinically and well as in the clinical studies. Thus, by preventing blood vessel leakage as well as abnormal blood vessel growth pegaptanib may be a viable approach for the treatment of CME. Although pegaptanib use has been associated with mild transient anterior segment inflammation CME itself has not been linked to its use. Besides, pegaptanib has been demonstrated to effect a sustainable decrease the macular edema in maculopathies, both age related and diabetic.
3. There is currently a need for considering alternative forms of local (ocular) therapy for CME to triamcinolone (sub tenon and intraocular). The serious adverse effects with intraocular corticosteroid use are well documented and include cataracts (nuclear and subcapsular), glaucoma, endophthalmitis (may be significantly higher than pegaptanib in patients who are treated exactly as per protocol) as well as sterile inflammatory reactions.

Eligibility criteria: Inclusion Criteria:

1. Male and female adults (\>18 years of age) with non infectious uveitis.
2. Demonstrable (FA and/or OCT) bilateral or unilateral CME associated with uveitis of greater than 3 months but less than 1 years duration that is documented by two independent qualified observers.
3. Best corrected VA between 20/40 and 20/200 as measured by the ETDRS chart attributable to CME in the study eye.
4. Patients may be receiving systemic therapy for the treatment of their intraocular inflammation or cystoid macular edema, or may have been treated for the cystoid macular edema in the past.
5. Anterior chamber inflammation equal to or greater than 1+ and vitreous inflammation equal to or greater than 1+ cell and 1+ haze as per the 'Standardization of Uveitis' working group definition.
6. Females of child bearing potential must agree to utilize effective contraception during the study and two months after the last dose of study medication.
7. Male study patients will agree to use effective contraception.
8. Ability to give informed consent.

Exclusion Criteria:

1. Allergy to pegaptanib or any of its components
2. Diabetic retinopathy, macular degeneration or any other ocular condition affecting the study eye that may cause vision loss or in the opinion of the study investigator would interfere with the evaluation of the efficacy of Macugen for the treatment of uveitis associated CME.
3. Refusal to try the therapeutic alternative pegaptanib
4. Lack of understanding of the consent or protocol
5. Suspicion/proved history or current diagnosis, (clinical or otherwise) of infectious uveitis.
6. Need for intraocular surgery within 30 weeks of study duration.
7. Periocular steroids to the study eye less than 6 weeks prior to study enrollment
8. History of any prior intravitreal injections in study eye
9. Systemic immunomodulatory agent(s) added or increased in dosage (\>20%) within the last two months prior to study enrollment, or potential need for any increase during the study.
10. Requirement for systemic corticosteroids in the equivalent of oral prednisone \> 30mg/day
11. Topical prostaglandin analog use
12. Severe debilitating disease or medical problems that make consistent follow-up over the treatment period unlikely (e.g. liver impairment, stroke, severe myocardial infarction, terminal cancer).
13. History of hypersensitivity to fluorescein or multiple drug allergies that may increase the chance of a drug reaction to Macugen.
14. Unclear media that precludes assessment of cystoid macular edema in eligible eye(s), such as a cataract or vitreal opacity.
15. Evidence of a macular hole in the study eye.
16. Prior or current retinal detachment in the study eye.
17. Concurrent treatment with any new investigational drug.
18. Pregnant or lactating women (Pregnant and lactating women are excluded since pregnancy may have some effect on CME).
19. Inability to comply with the study requirements.

Primary outcomes:
measure: Improvement in VA ETDRS >/= 15 Letters
timeFrame: 32 weeks
Secondary outcomes:
measure: Proportion of Patients Experiencing > 0 Letter Vision Gain and a < 15 Loss
timeFrame: 32 weeks
measure: Decrease in CME as Evidenced by Imaging (Fluorescein Angiography and 50 Micron Change in OCT)
timeFrame: 32 weeks
measure: A Decrease in Anterior Chamber Cells or Vitreous Cells or Haze in Injected Eye
timeFrame: 32 weeks
measure: Change in Immunomodulatory Medications (Topical, Periocular or Systemic) After the Initiation of Macugen Therapy
timeFrame: 32 weeks
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Eye Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Eye Center
name: Shree Kurup, MD
role: PRINCIPAL_INVESTIGATOR
References:
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