Clinical Trial Update

DRY AMD

Study: Anecorative Acetate Risk Trial (AART)

Sponsor: Alcon Research, Ltd.

Status: Enrollment is ongoing

Purpose: To demonstrate that anecortave acetate (15 mg or 30 mg) is safe and effective in arresting the progression of nonexudative AMD in patients who are at risk for progressing to exudative AMD

Design: Phase 3, double-masked, randomized, parallel group, no-treatment (sham administration), safety/efficacy study

Inclusion/Exclusion Criteria: Patients at least 50 years of age, any race and either sex, with a clinical diagnosis of exudative AMD in the nonstudy eye, and at least 5 or more intermediate (>63 microns) or larger soft drusen within 3000 microns of the foveal center and/or confluent drusen within 3000 microns of the foveal center, and hyperpigmentation within 3000 microns of the foveal center in the study eye.

Information: (866) 692-5959; http://www.alconlabs.com/us/eo/clinical studies

WET AMD

Study: Visudyne with Intravitreal Triamcinolone Acetonide (VisTA) Trial

Sponsor: LuEsther T. Mertz Retinal Research Center

Status: Recruiting

Purpose: To evaluate the effect of photodynamic therapy in conjunction with intravitreous triamcinolone acetonide in subjects with occult or minimally classic subfoveal CNV secondary to AMD

Design: Randomization 1:1:1, PDT and 0 mg of triamcinolone/PDT and 1 mg of triamcinolone/PDT and 4 mg of triamcinolone

Inclusion Criteria: 50 years or older, occult or minimally classic subfoveal CNV, presence of blood associated with the lesion, vision loss or growth of lesion objectively recorded within preceding 3 months, baseline VA score between 20/40­20/400, lesion ¾5400 microns

Exclusion Criteria: Predominantly classic CNV, additional eye disease, CNV not involving geometric center of FAZ, inability to be photographed; fluorescein allergy; photophobia; lens opacities expected to progress during study; previous treatment for CNV, other than confluent laser photocoagulation (eg, PDT, submacular surgery, radiotherapy, macular grid); participation in another clinical trial; IOP >21 mm Hg on or off meds; prior treatment with another antiangiogenic compound within 6 months of screening; inability to comply with all study-related procedures; concomitant therapy with systemic or topical Corticosteroids or NSAIDS (chronic concomitant therapy is defined as multiple doses taken daily for 3 or more consecutive days at any time during the course of the 12-month study); a low dose of ASA (up to 100 mg po qd) taken for prophylaxis of MI and/or stroke is permitted during the study; concomitant coumadin therapy

Number of Patients: 120

Information: Retina Associates of Cleveland, (216) 831-5700

Study: Preservative-free Triamcinolone Acetonide (PFTA)

Sponsor: QLT Inc., National Eye Institute

Status: Enrolling patients

Purpose: To investigate the long-term safety and potential efficacy of PFTA in patients with wet AMD (all types) undergoing Visudyne therapy

Design: Phase 3, randomized, prospective

Number of Patients: 300

Information: (301) 496-5248

Study: Combretastatin A-4 phosphate (CA4P) in patients with neovascular AMD (FBO-206)

Sponsor: Oxigene

Status: Enrolling patients

Purpose: Assess the safety and tolerability of combretastatin administered intravenously in patients with all forms of neovascular AMD (classic and occult)

Design: Phase 1/2, open label, safety and tolerability study. The study cycle consists of a prestudy evaluation period (2­4 weeks), a 22-day treatment period, and an 8-week post-treatment evaluation period

Number of Patients: 15­20

Site(s): 1, Wilmer Eye Institute, Baltimore, Md

Inclusion/Exclusion Criteria: 50 or older, study eye BCVA of 20/40 or less, fellow eye better or equal to 20/800 ETDRS, no history of previous subfoveal thermal laser therapy

Information: (781) 547-5912

Study: ANCHOR

Sponsor: Genentech

Status: Ongoing

Purpose: Evaluate the safety and efficacy of ranibizumab (Lucentis) compared with verteporfin photodynamic therapy in preventing vision loss associated with AMD

Design: Phase 3, randomized, double-blind, active control, parallel assignment. Three treatment arms: PDT and sham injection, sham PDT and Lucentis dose A, sham PDT and Lucentis dose B

Inclusion/Exclusion Criteria: 50 or older; predominantly classic; subfoveal CNV due to AMD; study eye BCVA equal to or worse than 20/40, but no worse than 20/320; lesion eligible for PDT per labeling; no prior laser treatment involving the center of the fovea; no prior PDT; no prior experimental treatments for AMD

Number of Patients: 426

Site(s): 100

Information: (888) 662-6728

Study: MARINA

Sponsor: Genentech

Status: Ongoing

Purpose: Evaluate safety, efficacy, and tolerability of 24 monthly intravitreal injections of ranibizumab (Lucentis) in preventing vision loss in patients with AMD

Design: Phase 3, multicenter, randomized, double-masked, 3 treatment arms: sham injection, 300 micrograms ranibizumab, and 500 micrograms ranibizumab

Inclusion/Exclusion Criteria: 50 and older; subfoveal wet AMD; study eye BCVA equal to or worse than 20/40, but no worse than 20/320; active, minimally classic or occult choroidal CNV due to AMD and not another cause; no previous subfoveal laser treatment; no previous verteporfin PDT; no previous experimental treatments for wet AMD

Number of Patients: 720

Site(s): 100

Information: (888) 662-6728

Study: An evaluation of safety and efficacy of anecortave acetate vs. placebo in patients with subfoveal CNV due to exudative AMD (C-02-29)

Sponsor: Alcon Research, Ltd.

Status: Enrollment is ongoing in South America

Purpose: To demonstrate that anecortave acetate 15 mg is superior to placebo in maintenance of visual acuity

Design: Phase 3, double-masked, randomized, parallel group, placebo-control, safety and efficacy study

Inclusion/Exclusion Criteria: Patients at least 50 years of age, any race and either sex with minimally classic and occult exudative AMD with subfoveal choroidal neovascularization

Information: Phone: 55-11-3732-4130

Study: Evaluation and tolerability of 4-dose levels of Cand5 administered by single intravitreal injection in patients with wet AMD

Sponsor: Acuity Pharmaceuticals

Status: Recruiting

Purpose: To evaluate 4-dose levels of the small RNA interference therapeutic agent Cand5 in subjects with exudative AMD

Design: Open label study. One intravitreal injection; 4-dose levels

Inclusion Criteria: Male or female patients 50 years of age or older, subfoveal CNV, classic or occult; total lesion size <12 total disc areas, of which at least 50% is active CNV; subretinal hemorrhage (if any)-no more than 50% of the lesion; minimally classic or occult lesion must have hemorrhage and/or lipid and or documented loss of 3 or more lines of vision during the previous 3 months; vision 20/50 to 20/320, with better acuity in the fellow eye; IOP ¾22 mm Hg

Exclusion Criteria: Concomitant ocular disease, 3 or more prior PDT treatments, thermal laser within the previous 2 weeks, subfoveal scarring or atrophy, h/o abdominal aortic aneurysm, stroke within previous 12 months, diabetes or use of oral hypoglycemics or insulin, h/o peripheral vascular disease, allergy to fluorescein

Number of Patients: 12

Site(s): 2

Information: (215) 966-6191; http://www.acuitypharm.com

Study: PIER

Sponsor: Genentech

Purpose: Trial designed to evaluate safety and efficacy of Lucentis in patients with wet AMD

Design: Lucentis phase 3b, randomized, double-masked, sham injection-controlled trial. Patients will be assigned to 1 of the following treatment arms: Lucentis Dose A,

Lucentis dose B, sham injection

Inclusion Criteria: Men and women age 50 and older; active primary or recurrent wet AMD involving the center of the fovea ("subfoveal"); best corrected visual acuity of equal to or worse than 20/40, but no worse than 20/320 in the study eye; classic or occult forms of CNV due to AMD and not another cause

Exclusion Criteria: Previous verteporfin photodynamic therapy, external beam radiation therapy, transpupillary thermotherapy or intravitreal drug delivery in the study eye, participation in any clinical trial involving antiangiogenic drugs (ie, ranibizumab, pegaptanib, anecortave acetate, protein kinase C inhibitors, etc.) or any other clinical trial within the last month

Number of patients: 180

Site(s): 3

Information: For inquiries about clinical trials, please submit a request through our information request form or call (888) 662-6728. For international inquiries, contact our international collaborator, Novartis Ophthalmics, at (866) 393-6336; http://www.novartisophthalmics.com.

Study: Trial to assess the effect of pegaptanib sodium on foveal thickening in patients with exudative subfoveal AMD

Sponsor: Eyetech Pharmaceuticals

Status: Recruiting

Purpose: To compare the safety of Macugen with that of sham treatment and to assess Macugen's effect on foveal thickening

Design: Phase 2 prospective, randomized, double-masked, sham-controlled, dose-ranging, multicenter trial. First 3 injections: randomization, 1:1:1, 0.3 mg/1 mg/sham; subjects in sham treatment group subsequently rerandomized to 0.3 mg or 1 mg

Inclusion Criteria: CNV with total lesion size of 12 DA or less of which at least 50% is active CNV, subretinal hemorrhage not more than 50% of total lesion size, no subfoveal scarring, atrophy, or fibrosis or blood over fovea, no more than 25% of the total lesion made up of scarring or atrophy, for minimally classic or occult lesions: >=3 line vision loss during the previous 12 week and/or subretinal hemorrhage (not more than 50% of the total lesion size), VA approximately 20/40-20/320 in study eye and 20/800 or better in fellow eye, foveal thickness on OCT >=300 mm, classic CVN for which PDT can be deferred for 54 weeks

Exclusion Criteria: Previous subfoveal thermal laser or PDT laser; intraocular surgery, including extrafoveal/juxtafoveal laser within the previous 3 months; h/o PPV or SB; pigment epithelial tears or rips; any other conditions that may be causing CNV, diabetic retinopathy; h/o stroke within 12 months of study entry; h/o peripheral vascular disease or severe cardiac disease; significant hematologic, renal, or hepatic disease

Information: Retina Associates of Cleveland, (216) 831-5700

Study: Squalamine

Sponsor: Genaera Corporation

Status: Enrolling patients

Purpose: To evaluate the safety and efficacy of intravenously administered squalamine as a first-line therapy for wet AMD

Design: Phase 2, randomized, double-masked, controlled study; 2 dose levels once weekly for 4 weeks, followed by maintenance doses once every 4 weeks through week 48. At the end of therapy, each patient will be followed for an additional year

Number of Patients: 100

Site(s): Multicenter

Information: (610) 941-4020

Study: Noncomparative protocol for use of 0.3 mg intravitreous Macugen injections every 6 weeks in patients with AMD

Sponsor: Eyetech Pharmaceuticals

Status: Recruiting

Purpose: To provide Macugen to patients who have subfoveal CNV secondary to AMD and who are unable to participate in any other clinical studies of Macugen for AMD, until such time as the patient's lesion is considered to have resolved or stabilized or Macugen becomes commercially available

Design: Open label study, 0.3 mg intravitreous injection

Inclusion Criteria: CNV with total lesion size of 12 DA or less of which at least 50% is active CNV; subretinal hemorrhage not more than 50% of the total lesion size; no subfoveal scarring, atrophy, or fibrosis; no more than 25% of the total lesion is scarring or atrophy; VA approximately 20/40-20/320 in the study eye; no fellow eye requirement; IOP ¾23

Exclusion Criteria: Eligibility for PDT with Visudyne (including patients for whom prior PDTs have been deemed ineffective), eligibility for any other Macugen trials, presence of other causes of CNV - myopia > 8 diopters, ocular histoplasmosis, angioid streaks, choroidal rupture, multifocal choroiditis, h/o severe cardiac disease, MI within previous 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina, stroke within previous 12 months, acute ocular or periocular infection, serious allergy to FA

Information: Retina Associates of Cleveland, (216) 831-5700

Study: PrONTO

Sponsor: Bascom Palmer Eye Institute and Genentech, Inc

Status: Recruiting

Purpose: To determine how quickly the central retinal thickness decreases following ranibizumab (Lucentis) therapy using OCT and then, after 3 monthly doses, determine the durability of the treatment response with intermittent therapy offered only if needed based on OCT findings

Design: Prospective, open-label, uncontrolled, clinical study

Inclusion Criteria: Neovascular AMD; subfoveal CNV; all lesion types; recent disease progression, central retinal thickness at least 300 microns; multiple visits required--6 visits each month for the first 3 months, then visits once a month thereafter for a total of 2 years

Information: Maria Esquiabro, (305) 326-6508; Dr. Philip Rosenfeld, (305) 326-6148

Study: Study of the safety and efficacy of AG-013958 in subjects with subfoveal choroidal neovascularization associated with age-related macular degeneration

Sponsor: Pfizer

Status: Recruiting

Purpose: To assess the safety, efficacy, and pharmacokinetics of the investigational drug AG-013958 in subjects with exudative AMD

Design: Phase 1/2, randomized, masked, single and multiple-dose, single and multiple-dose, sequential dose-escalation

Inclusion Criteria: AMD, minimally classic & occult-classic eligible in stage II of study (after first 46 pts), no subfoveal fibrosis; total lesion fibrosis or scar <25% total area; hemorrhage <50% of total lesion area, total lesion area ¾9 DA; ETDRS best corrected score of approximately 20/40-20/230; fellow eye VA >=24 letters (20/320 or better); normal ECG or nonsignificant changes

Exclusion Criteria: Prior PDT >3 months before entry; serous pigment epithelial detachment without surrounding neovascularization; diabetic retinopathy, glaucoma, or other serious ocular diseases or conditions; prior subfoveal photocoagulation of the macula; prior intravitreal, sub-Tenon's, or systemic therapy for AMD; prior TTT (transpupillary thermotherapy) or intravitreal steroids in study eye or likely to undergo these procedures within 6 months of entry; cataract surgery within previous 12 months; intraocular surgery within previous 3 months; prior vitrectomy or submacular surgery; prior scleral buckling, myopia >= 6 diopters; sitting BP >159/99 mm Hg on 2 out of 3 evaluations; stroke within the previous 12 months; h/o severe cardiac disease; peripheral vascular disease; unstable angina; MI within 6 months; ventricular tachycardia requiring treatment; inability to stop anticoagulants 4 days prior to injection (ASA okay to continue); participation in any clinical trials within the previous 60 days; use of systemic steroids currently or within the previous 30 days

Information: Retina Associates of Cleveland, (216) 831-5700

Study: TheraSight Ocular Brachytherapy System for Treatment of AMD

Sponsor: Theragenics Corporation

Number of Patients: 30

Status: Enrolling

Purpose: To investigate the safety, feasibility, and tolerability of the TheraSight' Brachytherapy System for treatment of wet AMD

Design: A multicenter, randomized study of 3 doses of radiation (assigned 1:1:1) delivered by the TheraSight Brachytherapy System in participants with CNV secondary to AMD

Inclusion Criteria: Age 50 years or older; active primary or recurrent subfoveal CNV secondary to AMD with minimally classic or occult lesion; where an active lesion is defined, lesion < 6 mm greatest linear dimension (GLD); submacular blood must comprise less than 75% of the total lesion; subretinal fibrosis must comprise less than 25% of the total lesion; study eye best-corrected vision of 20/100 or poorer measured on an ETDRS chart
(<48 letters correct), fellow eye best-corrected vision that is at least 1 line better on an ETDRS chart than the best-corrected vision of the study eye; HbA1c <6%, signed informed consent

Exclusion Criteria: Prior AMD therapy treatment, including but not limited to laser and photodynamic therapy; prior ophthalmic surgery for the study eye other than cataract extraction and/or capsulotomy; presence of other eye diseases that could compromise visual acuity in the study eye or that, in the clinical judgment of the evaluating study ophthalmologist, might create special risk for the study participant; CNV due to other causes such as ocular histoplasmosis or pathologic myopia, endstage fibrotic disciform lesions; diabetes requiring diet modification, medication, or insulin; current history of malignancy (except participants having basal cell carcinoma that was treated successfully, or other malignancy operated on or treated and in remission for 5 years prior to inclusion in the trial); hypertensive retinopathy, major cardiovascular or cerebrovascular event within the last year; inability to complete follow-up; allergy to fluorescein dye; previous radiation to the study eye; pregnancy at time of surgical procedure

Information: 1-877-960-1234; http://www.theragenics.com

RETINAL DETACHMENT

Study: Denufosol tetrasodium (INS37217 Ophthalmic), P2Y2 receptor agonist for intravitreal injection

Sponsor: Inspire Pharmaceuticals

Status: Enrolling patients

Purpose: To compare the safety and efficacy of INS37217 Ophthalmic to placebo as a first-line therapy in patients with rhegmatogenous retinal detachment

Design: Phase 2, double-masked, randomized, placebo-controlled, parallel-dose. Patients will be given a single intravitreal injection of drug or placebo and allows for up to 2 additional consecutive daily injections for patients who show signs of improvement following the previous injection

Inclusion Criteria: Rhegmatogenous retinal detachment (RRD) in only 1 eye; >=18 years of age; no more than 3 separate breaks; all breaks must be clustered together and confined within an area that is no more than 2 clock hours in extent on the fundus; total area of all open breaks in the detached part of the retina is no greater than 1 clock hour in extent; retinal detachment is large enough that it cannot be immediately repaired with laser or cryo (eg, accumulated subretinal fluid extends at least 3 disk diameters from the edges of the break); macula on­VA 20/50 or better in both eyes, macula off­VA 20/50 nonstudy eye, plus history prior to this detachment of reading capability in the study eye

Exclusion Criteria: Nonrhegmatogenous (tractional or exudative); large break whose total break is greater than 1 clock hour in extent; atrophic RPE or choroid; choroidal detachment; demarcation lines; coexisting pathology; > 0.8 cup/disc ratio; prior RD repair (surgical or nonsurgical); peribulbar, retrobulbar, or intravitreal corticosteroid treatment within the previous 3 months; symptoms consistent with RRD, such as visual disturbance (specifically shadows or curtains) for >14 days prior to screening if macula-on or h/o loss of reading vision in the study eye for more than 6 days prior to screening if macula-off, if macula-off and enrolled in study, subject must be able to receive study drug injections (possibly up to 3) and be repaired or rescued all by the 10th day of the detachment. If enrolled in the study, subject must not be macula-off for >10 days; ongoing treatment with Diamox or Trusopt (dorzolamide); h/o drug or alcohol dependence in the last year; known sensitivity to P2Y2

Number of Patients: 160

Site(s): 25

Results Expected: Mid-2005

Information: (919) 941-9777, Ext. 245

DIABETIC MACULAR EDEMA

Study: Pegaptanib sodium injection (Macugen)

Sponsor: Eyetech Pharmaceuticals and Pfizer Inc.

Status: No longer enrolling patients. Study completion expected Q1 2005

Purpose: To compare the safety and efficacy of pegaptanib with placebo in patients with DME

Design: Phase 2, multicenter, randomized, placebo-control, double-masked. Patients received varying doses (0.3 mg, 1 mg, 3 mg) of drug or sham injection every 6 weeks for at least 12 weeks and then at the discretion of the investigators

Inclusion/Exclusion Criteria: Eligibility for thermal laser therapy for DME

Number of Patients: 169

Site(s): 41

Information: (212) 824-3100

Study Name: Reduction in the occurrence of center-threatening DME

Sponsor: Eli Lilly and Company

Status: Recruiting

Purpose: To determine whether ruboxistaurin can slow the progression of DME

Design: Randomization 1:1, ruboxistaurin/ placebo

Inclusion Criteria: Macular edema: if >= 1/6 DA up to < 1DA, location must be> 500 mm Þ £ 3000 mm from center of macula or if >=1 DA location must be >1500 mm Þ £ 3000 mm from center of macula, ETDRS retinopathy level of >=20 and £ 47D in the study eye, best refracted visual acuity in the study eye of 20/32 or better

Exclusion Criteria: H/o any focal, grid, or scatter laser for DME in the study eye; glaucoma (ocular hypertension in the absence of a glaucomatous visual field defect is acceptable); retinal artery/vein occlusions, macular degeneration, chorioretinal scars; any intraocular surgery, including YAG laser, within the previous 6 months; preretinal or vitreous hemorrhage (currently); treatment for DME with any therapy, including intravitreal or sub-Tenon's steroid, in the previous 6 months; h/o vitrectomy; poorly controlled DM (HA1c >11%), hypertension greater than 170 systolic; chronic renal failure on dialysis; s/p renal transplant or creatinine >4.0; treatment with or planned treatment with topical or oral carbonic anhydrase inhibitors; participation in previous Lilly ruboxistaurin study

Information: Retina Associates of Cleveland, (216) 831-5700

Study: Intravitreal triamcinolone acetonide and laser photocoagulation for DME

Sponsor: Diabetic Retinopathy Clinical Research Network

Status: Recruiting

Purpose: To determine whether intravitreal triamcinolone at doses of 1 mg or 4 mg provides greater benefit, with an acceptable safety profile, than macular laser in the treatment of DME

Design: One eye eligible: randomization, 1:1:1, laser/1 mg triamcinolone/4 mg triamcinolone. Both eyes eligible: 1 eye randomized to laser, the other to 1 mg or 4 mg of triamcinolone

Inclusion/Exclusion Criteria: Age >=18 years, study eye with best corrected E-ETDRS acuity >24 letters (20/320 or better) and <68 letters (worse than 20/40), study eye with center-involved DME present on clinical exam and on OCT, mean retinal thickness on 2 OCT measurements >250 microns in the central subfield, fellow eye either eligible or has acuity >19 letters (20/400 or better); has not been previously treated with intravitreal corticosteroids

Number of Patients: 795 patients

Site(s): 1

Information: http://public.drcr.net/studies/ProtocolB_steroid/ProtBInfo.html

Study: Laser photocoagulation for DME

Sponsor: Diabetic Retinopathy Clinical Research Network (DRCR.net)

Status: Recruiting

Purpose: To compare standard laser treatment with mild, macular-grid treatment that is milder in intensity, but more extensive in number of laser burns

Design: Pilot Study. One eye eligible: randomization, 1:1, standard/mild macular grid. Both eyes eligible: 1 eye randomized to 1 of the treatments, the other eye randomized to the other treatment

Inclusion/Exclusion Criteria: Age >=18 years, study eye with best corrected E-ETDRS acuity >19 letters (20/400 or better), definite retinal thickening due to diabetic macular edema based on clinical exam at or within 500 microns of the macular center for which the investigator believes laser photocoagulation is indicated, a thickness of 250 microns or more in the central subfield OR a thickness of 300 microns or more in any 1 of the 4 subfields directly adjacent to the central subfield on OCT

Number of Patients: Approximately 200 patients

Site(s): 1

Information: http://public.drcr.net/studies/ProtocolA_laser/ProtAInfo.html

CENTRAL RETINAL VEIN OCCLUSION

Study: The Standard Care vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study: to compare the efficacy and safety of intravitreal injection(s) of triamcinolone acetonide with standard care to treat macular edema: 1 for CRVO and 1 for BRVO

Sponsor: National Eye Institute, National Institutes of Health, Department of Health and Human Services

Status: Enrollment began in October 2004

Purpose: To compare the effectiveness and safety of standard care to intravitreal injection(s) of triamcinolone for treating macular edema (swelling of the central part of the retina) associated with CRVO and BRVO

Design: Multicenter, randomized, phase 3 trial designed to assess the efficacy and safety of standard care versus triamcinolone acetonide injection(s) for the treatment of macular edema associated with CRVO and BRVO. Eligible patients within each of these 2 disease entities are randomized in a 1:1:1 ratio to 1 of 3 groups: standard care, intravitreal injection(s) of 4mg of triamcinolone acetonide, or intravitreal injection(s) of 1mg of triamcinolone acetonide. Enrolled patients are followed for 3 years. The preparation of triamcinolone acetonide used in the study is specially made for injection into the eye and does not contain any preservatives

Inclusion/Exclusion Criteria: Participants with macular edema (swelling of the central part of the retina) associated with CRVO and BRVO who are 18 years of age or older and are willing to provide consent. Detailed Inclusion/Exclusion Criteria are available on the SCORE Web site at http://spitfire.emmes.com/study/score/.

Number of Patients: 1260; 630 with CRVO and 630 with BRVO

Site(s): 27

Information: (301) 251-1161; http://spitfire. emmes.com/study/score/; E-mail: score@emmes.com