A PHASE 2, RANDOMIZED, DOUBLE-MASKED, CONTROLLED TRIAL TO ESTABLISH THE SAFETY AND EFFICACY OF INTRAVITREOUS INJECTIONS OF E10030 (ANTI-PDGF PEGYLATED APTAMER) GIVEN IN COMBINATION WITH LUCENTIS® IN SUBJECTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION - REGRESS

Phase 1

• Conditions: Subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD); MedDRA version: 12.1Level: LLTClassification code 10064930Term: Age-related macular degeneration; MedDRA version: 12.1Level: LLTClassification code 10067791Term: Wet macular degeneration

• Registration Number: EUCTR2010-018741-65-BE
• Lead Sponsor: OPHTHOTECH CORPORATIO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03-09
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 444

Inclusion Criteria

8.2.1Ophthalmic Inclusion Criteria
The following inclusion criteria apply to the study eye:
8.2.1.1Subfoveal choroidal neovascularization (CNV) due to AMD with some classic component (i.e., predominantly classic or minimally classic) as documented by fluorescein angiogram.
8.2.1.2Best corrected visual acuity in the study eye between 20/63 and 20/200, inclusive. The VA must be re-confirmed at Day 0 prior to randomization.
8.2.1.3Total area of the lesion (including blood, neovascularization, and scar/atrophy) must be = 5 disc areas (DA), of which at least 50% must be active CNV. Active CNV is defined as the neovascular component of the lesion as defined by the fluorescein angiogram.
8.2.1.4Presence on OCT of subretinal fluid and/or cystoid macular edema and an abnormal central retinal thickness defined as:
•Stratus central subfield > 250 microns
•Topcon central subfield > 290 microns
•Cirrus central subfield > 300 microns
•Heidelberg central subfield > 210 microns
8.2.1.5Clear ocular media and adequate pupillary dilatation to allow collection of fundus photographs and fluorescein angiograms of a sufficient quality to be analyzed by the central reading center.
8.2.1.6Intraocular pressure (IOP) of 21 mmHg or less.

8.2.2General Inclusion Criteria
8.2.2.1Subjects of either gender, aged greater than or equal to 50 years.
8.2.2.2Performance Status = 2 according to Eastern Cooperative Oncology Group (ECOG) / World Health Organization (WHO) scale (Appendix 17.4)
8.2.2.3Women must agree to be using two forms of effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile; if of child-bearing potential, a serum pregnancy test must be performed within 14 days prior to the first injection with a negative result. The two forms of effective contraception must be implemented during the trial and for at least 60 days following the last dose of test medication.
8.2.2.4Adequate hematological function: hemoglobin greater than or equal to 10g/dL; platelet count greater than or equal to 130 x 10E9/L; WBC greater than or equal to 3.8 x 10E9/L. Subjects with results outside these ranges may be enrolled in consultation with Ophthotech.
8.2.2.5Adequate renal function: serum creatinine = 2.5 mg/dl (= 221µmol/L) and BUN within 2 x the upper limit of normal (ULN). Subjects with results outside these ranges may be enrolled in consultation with Ophthotech.
8.2.2.6Adequate liver function: serum bilirubin = 1.5 mg/dl (= 25.6 µmol/L), GGT, SGOT/ALT, SGPT/AST, and alkaline phosphatase within 2 x ULN. Subjects with results outside these ranges may be enrolled in consultation with Ophthotech.
8.2.2.7Provide written informed consent.
8.2.2.8Ability to comply with study and follow-up procedures and return for all trial visits.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects will not be eligible for the trial if any of the following criteria are present in the study eye or systemically:
8.3.1Ophthalmic Exclusion Criteria
8.3.1.1Any prior treatment for AMD in the study eye prior to the baseline visit, except oral supplements of vitamins and minerals.
8.3.1.2Any prior intravitreal treatment in the study eye prior to the baseline visit, regardless of indication (including intravitreal corticosteroids).
8.3.1.3More than 25% of the total lesion size made up of scarring or atrophy. Subjects with subfoveal scar or subfoveal atrophy are excluded.
8.3.1.4More than 50% of the total lesion size consisting of subretinal hemorrhage.
8.3.1.5Presence of retinal angiomatous proliferation (RAP).
8.3.1.6Presence of significant pigment epithelial detachments (PEDs) such as large PEDs that constitute greater than 50% of the total lesion.
8.3.1.7Presence of pigment epithelial tears or rips.
8.3.1.8Presence of intraocular inflammation (= trace cell or flare), epiretinal membrane, macular hole or vitreous hemorrhage.
8.3.1.9Aphakia or absence of the posterior capsule. Absence of an intact posterior capsule is allowed if it occurred as a result of YAG laser posterior capsulotomy in association with prior posterior chamber IOL implantation.
8.3.1.10History of idiopathic or autoimmune-associated uveitis in either eye.
8.3.1.11Significant media opacities, including cataract, which might interfere with visual acuity, assessment of toxicity, or fundus photography in the study eye. Subjects should not be entered if there is likelihood that they will require cataract surgery in the study eye in the next 12 months.
8.3.1.12Presence of other causes of choroidal neovascularization, including pathologic myopia (spherical equivalent of -8 diopters or more, or axial length of 25mm or more), the ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, and multifocal choroiditis.
8.3.1.13Any intraocular surgery or thermal laser within three (3) months of trial entry. Any prior thermal laser in the macular region, regardless of indication.
8.3.1.14Any ocular or periocular infection in the past twelve (12) weeks.
8.3.1.15History of any of the following conditions or procedures in the study eye: Rhegmatogenous retinal detachment, pars plana vitrectomy, filtering surgery (e.g. trabeculectomy), glaucoma drainage device, corneal transplant.
8.3.1.16Previous therapeutic radiation in the region of the study eye.

8.3.2General Exclusion Criteria
8.3.2.1Any of the following underlying diseases including:
•Diabetes mellitus
•History or evidence of severe cardiac disease (e.g., NYHA Functional Class III or IV - see Appendix 19.6), history or clinical evidence of unstable angina, acute coronary syndrome, myocardial infarction or coronary artery revascularization within 6 months, or ventricular tachyarrythmias requiring ongoing treatment.
•Clinically significant impaired renal (serum creatinine >2.5 mg/dl or s/p renal transplant or receiving dialysis) or hepatic function.
•Stroke (within 12 months of trial entry).
•Any major surgical procedure within one month of trial entry.
8.3.2.2Any treatment with an investigational agent in the 60 days prior to randomization for any condition.
8.3.2.3Known serious allergies to the fluorescein dye used in angiography (mild allergy amenable to treatment is allowable), to the components of the ranibizumab formulation, or to the components of the E10030 formulation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objectives of this study are to evaluate the safety and efficacy profile of E10030 intravitreous injection when administered in combination with Lucentis® 0.5 mg/eye against a control of Lucentis® 0.5 mg/eye alone in subjects with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD);Secondary Objective: Not applicable;Primary end point(s): The primary efficacy endpoint is the proportion of subjects gaining at least 15 ETDRS letters between baseline and the Week 12 visit.