High-Dose Lucentis (Ranibizumab 2.0mg) for the Treatment of Nonproliferative Idiopathic Parafoveal Telangiectasia

DESCRIPTION OF THE STUDY

This is an open-label, Phase I/II study of intravitreally administered ranibizumab in subjects with nonproliferative Idiopathic Parafoveal Telangiectasia (IPT).

Consented, enrolled subjects will be randomized into two groups: observation and treatment. The observation group will be monitored monthly while the treatment group will receive three open-label intravitreal injections of 1.0 mg ranibizumab administered every 30 days for 3 months and then as needed monthly, based on defined criteria. NOTE: The original protocol had the treatment group dosed at 2.0 mg/0.05mL. However, the 2.0mg dose will become unavailable beginning January 31, 2012. Therefore, the protocol amendment submitted in December 2011 changed the 2.0mg arm to a 1.0mg/ 0.10mL arm. Please note that three patients were already treated with 2.0mg before the amendment was submitted, so they will be switched to 1.0mg if they have not completed the study when the 2.0 dose is no longer available in January 2012.

Protocol: FVF4875s Final 6/P

29MAR2010

3.2

RATIONALE FOR STUDY DESIGN

As IPT is a chronically progressive condition, the purpose of this study is to see if high-dose ranibizumab can slow or stop the leakage and growth of existing, dilated, macular vessels in cases where no co-existing neovascularization exists as defined by fluorescein angiography and Ocular Coherence Tomography (OCT). Other outcomes include stabilization of visual acuity compared to observation group (defined by best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) measurements), and changes in ultrastructural features, as defined by OCT,

3.3

OUTCOME MEASURES

3.3.1 Primary Outcome Measures

To compare the change in visual acuity from baseline to one year in patients with nonproliferative IPT who are either treated with high-dose (1.0mg) ranibizumab or observed.

3.3.2 Secondary Outcome Measures

i. To compare the change in visual acuity from baseline to 6 months and 9 months in patients with nonproliferative IPT who are either treated with high- dose (1.0mg) ranibizumab or observed.

ii. To assess OCT changes in standard Central Subfield Thickness (CST) from baseline to 6 months, 9 months and 12 months.

iii. To assess safety of administering 1.0mg ranibizumab (Lucentis) in patients with nonproliferative IPT at 6 months, 9 months and 12 months.

iv. To assess changes in angiographic leakage from baseline at 6 and 12 months.

Inclusion criteria

• Ability to provide written informed consent and comply with study assessments for the full duration of the study
• Age > 18 years
• Presence of nonproliferative IPT confirmed by fluorescein angiography and spectral-domain OCT
• Age greater than 18
• Vision equal to or worse than 20/25 and better than or equal to 20/400 by ETDRS chart, without co-existing choroidal neovascularization.
• Physical ability and reasonable expectation to maintain all follow-up appointments.

Exclusion criteria

• Pregnancy (positive pregnancy test) or lactation
• Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.
• 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 ophthalmologic investigation or trial
• Any patient with proliferative diabetic retinopathy, diabetic macular edema, uveitis, history of ocular trauma, severe glaucoma, neovascular age-related macular degeneration
• Duration of previous treatment of IPT that exceeds two years.
• Any concurrent intraocular condition in the study eye (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, could either:
• Require medical or surgical intervention during the 12-month study period to prevent or treat visual loss that might result from that condition, or
• If allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of Best Corrected Visual Acuity (BCVA) over the study period
• Prior/Concomitant Treatment:
• Previous steroids (oral) within 30 days preceding Day 0
• Previous participation in any studies of investigational drugs within 30 days preceding Day 0 (excluding vitamins and minerals)
• Prior participation in a Genentech ranibizumab clinical trial within 60 days.
• History of receiving intravitreal injections of ranibizumab, bevacizumab, pegaptanib, or any other intravitreal medication within 60 days of first injection. History of receiving intravitreal or subtenons triamcinolone within 90 days of first injection.