Lucentis for Inflammatory Macular Edema Trial

Uveitis Clinical Trial

— LIME  

Official title:

Effect of Ranibizumab on Refractory Macular Edema in Uveitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00498355
• Other study ID #: FVF3872s
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 9, 2007
• Last updated: October 24, 2017
• Start date: July 2007
• Est. completion date: December 2009

Study information

• Verified date: October 2017
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Uveitis is an inflammation (swelling and irritation) inside the eye, affecting the uvea. The uvea is the layer of the eye between the sclera and the retina and provides most of the blood supply to the retina.

Uveitis is an important cause of visual loss. There are 30,000 new cases of legal blindness each year due to uveitis in the U.S. Sight-threatening complications associated with uveitis include macular edema, which may persist even when inflammation is controlled. The only current treatment for cystoid macular edema (CME) in uveitis patients is oral or regional steroid injections. For patients who don't respond to steroids or who are unable to tolerate steroid therapy, there are no other medical treatments.

The aim of this study is to determine if ranibizumab, an FDA-approved treatment for neovascular age-related macular degeneration, is an effective treatment for those patients with uveitis-induced CME who are unable to be treated with or non-responsive to steroids.

Description:

Uveitis, an inflammation that affects the uvea (iris, ciliary body and choroid), is an important cause of visual loss. There are 30,000 new cases of legal blindness each year due to uveitis in the U.S. Sight-threatening complications associated with uveitis include macular edema, which may persist even when inflammation is controlled. The only current treatment for cystoid macular edema (CME) in uveitis patients is oral or regional steroid injections. For patients who don't respond to steroids or who are unable to tolerate steroid therapy, there are no other medical treatments.

The aim of the proposed research is to determine if ranibizumab is an effective treatment for those patients with uveitis-induced CME who are unable to be treated with or non-responsive to steroids. Ranibizumab is a recombinant, humanized monoclonal antibody antigen-binding fragment (Fab) that neutralizes all active forms of vascular endothelial growth factor (VEGF). VEGF is suspected to play a role in the loss of vascular integrity in the eye, which is thought to be involved in the pathogenesis of macular edema in the eyes of patients with uveitis. Ranibizumab was approved by the FDA for the treatment of neovascular age-related macular degeneration on June 30, 2006, and a number of published papers have shown efficacy for other causes of macular edema, including that due to diabetes mellitus.

The F. I. Proctor Foundation at UCSF will be enrolling 10 subjects 18 years of age or older with uveitis-induced CME to clinically evaluate the safety and effectiveness of ranibizumab administered monthly for three months followed by PRN monthly dosing (up to 12 months). The study will measure visual acuity, changes in foveal thickness on optical coherence tomography, and changes in cystoid macular edema by fluorescein angiography to determine the efficacy of ranibizumab treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: December 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study

• Age = 18 years

• A history of non-infectious uveitis with chronic cystoid macular edema (> 3 months duration)

• Foveal retinal thickness of = 300 µM by OCT testing

• One prior trial of oral or regional steroid treatment for CME = 30 days prior to study enrollment with persistent CME (= 300 µM foveal retinal thickness on OCT) or inability to use steroid injections due to a history of increased IOP above 30 mmHg thought to be due to topical steroid treatment or prior steroid injections

• Anterior chamber and vitreous inflammation at the trace or below level according to the standardized classification of inflammation

• BCVA at 4 m using the ETDRS chart of 20/40 to 20/400 (Snellen equivalent) in the study eye

• Media clarity, pupillary dilation and patient cooperation sufficient to allow OCT testing and retinal photography

Exclusion Criteria:

• Pregnancy (positive pregnancy test) or known to be pregnant, or premenopausal but not using adequate contraception

• Treatment for CME with oral or steroid injections, Macugen, or Avastin within 6 weeks prior to enrollment in this study. Study subjects will be allowed to continue their immunomodulatory treatment for uveitis throughout the study.

• Previous vitrectomy

• Active intraocular inflammation in the study eye (greater than trace anterior chamber or vitreous cells)

• Current vitreous hemorrhage

• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye

• Known allergy to any component of the study drug

• Intraocular pressure > 30 mm Hg despite treatment with glaucoma medications

• Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). If blood pressure is brought below 180/110 by anti-hypertensive treatment, the subject can become eligible.

• Major surgery planned during the next 6 months

• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated

• Participation in another simultaneous medical investigation or trial

• Unwilling or unable to follow or comply with all study related procedures

Related Conditions & MeSH terms

• Cytoid Macular Edema
• Edema
• Macular Edema
• Uveitis

Intervention

Drug:
• Ranibizumab
0.5 mg of ranibizumab by intravitreal injection at baseline and at monthly intervals for the following two months for a total of 3 injections. Afterwards, PRN injections for 9 months.

Locations

Country	Name	City	State
United States	Proctor Foundation, UCSF	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Mean Change at 3 Months in BSCVA From Baseline	The outcome measure was mean best spectacle-corrected visual acuity (BSCVA). In this study, BSCVA was measured after trial frame manifest refraction, using high-contrast modified Bailey-Lovie (ETDRS) charts at 4 meters. The charts were placed in a retro-illuminated light box equipped with two 20-watt fluorescent tubes. The highest attainable 4-meter visual acuity score is 100 letters.	baseline and 3 months
Secondary	The Median Change in Best Corrected Visual Acuity From 6 to12 Months		6 to 12 months
Secondary	The Mean Change in Foveal Retinal Thickness From Baseline at 7 Days, and at Months 3, 6, 9, and 12		7 days, and at months 3, 6, 9, and 12
Secondary	The Incidence of Uveitis Flares (> 2+ Cells in the Anterior Chamber or Vitreous)		Study duration
Secondary	The Incidence of Ocular and Non-ocular Adverse Events		Study duration