| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10067791 |
| E.1.2 | Term | Wet macular degeneration |
| E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10064930 |
| E.1.2 | Term | Age-related macular degeneration |
| E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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 versus monotherapy Lucentis® 0.5 mg/eye in subjects with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects must meet the following criteria to be eligible to participate in this study.
8.2.1 Ophthalmic Inclusion Criteria
The following inclusion criteria apply to the study eye:
8.2.1.1 Subfoveal choroidal neovascularization (CNV) due to AMD with some classic component (i.e., predominantly classic or minimally classic) as documented by fluorescein angiogram.
8.2.1.2 Best 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.
8.2.1.3 Total 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.
8.2.1.4 Presence on OCT of subretinal, intraretinal or sub-RPE fluid and/or subretinal thickening consistent with active CNV.
8.2.1.5 Clear 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.
8.2.1.6 Intraocular pressure (IOP) of 21 mmHg or less.
8.2.2 General Inclusion Criteria
8.2.2.1 Subjects of either gender, aged 50 years.
8.2.2.2 Performance Status 2 according to Eastern Cooperative Oncology Group (ECOG) / World Health Organization (WHO) scale (Appendix 17.4)
8.2.2.3 Women 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.
8.2.2.4 Adequate hematological function: hemoglobin 10g/dL; platelet count 130 x 109/L; WBC 3.8 x 109/L. Subjects with results outside these ranges may be enrolled in consultation with Ophthotech.
8.2.2.5 Adequate 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.
8.2.2.6 Adequate 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.
8.2.2.7 Provide written informed consent.
8.2.2.8 Ability to comply with study and follow-up procedures and return for all trial visits. |
|
| E.4 | Principal exclusion criteria |
Subjects will not be eligible for the trial if any of the following criteria are present in the study eye or systemically:
8.3.1 Ophthalmic Exclusion Criteria
8.3.1.1 Any prior treatment for AMD in the study eye prior to the baseline visit, except oral supplements of vitamins and minerals.
8.3.1.2 Any prior intravitreal treatment in the study eye prior to the baseline visit, regardless of indication (including intravitreal corticosteroids).
8.3.1.3 More than 25% of the total lesion size made up of scarring or atrophy. Subjects with subfoveal scar or subfoveal atrophy are excluded.
8.3.1.4 More than 50% of the total lesion size consisting of subretinal hemorrhage.
8.3.1.5 Presence of retinal angiomatous proliferation (RAP).
8.3.1.6 Presence of significant serous pigment epithelial detachments (PEDs), such as large PEDs that constitute greater than 50% of the total lesion.
8.3.1.7 Presence of pigment epithelial tears or rips.
8.3.1.8 Presence of intraocular inflammation (≥ trace cell or flare), significant epiretinal membrane or vitreomacular traction, macular hole or vitreous hemorrhage.
8.3.1.9 Aphakia 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.
8.3.1.10 History of idiopathic or autoimmune-associated uveitis in either eye.
8.3.1.11 Significant 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.
8.3.1.12 Presence 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.
8.3.1.13 Any intraocular surgery or thermal laser within three (3) months of trial entry. Any prior thermal laser in the macular region, regardless of indication.
8.3.1.14 Any ocular or periocular infection in the past twelve (12) weeks.
8.3.1.15 History 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.
8.3.1.16 Previous therapeutic radiation in the region of the study eye.
8.3.2 General Exclusion Criteria
8.3.2.1 Any of the following underlying diseases including:
• Diabetes mellitus, also defined as an HbA1c level ≥ (greater than or equal to) 6.5%.
• History or evidence of severe cardiac disease (e.g., NYHA Functional Class III or IV - see Appendix 17.6), 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.
8.3.2.2 Any treatment with an investigational agent in the 60 days prior to randomization for any condition.
8.3.2.3 Known 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.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the mean change in visual acuity from baseline at the Week 24 visit. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints of the trial, in order of importance, include:
•The proportion of subjects gaining 15 or more ETDRS letters from baseline at the Week 24 visit.
•The proportion of subjects gaining 15 or more ETDRS letters from baseline at the Week 12 visit.
•The mean change in area of choroidal neovascularization from baseline at Week 24 (by fluorescein angiogram).
•The mean change in visual acuity from baseline at Week 12.
Principal supportive endpoints include:
•The mean change in area of choroidal neovascularization from baseline at Week 12 (by fluorescein angiogram).
•The mean change in total lesion size from baseline at Week 12 and 24.
•The mean change in central subfield retinal thickness from baseline at Week 12 and 24 (by OCT).
•The proportion of patients with RPE elevation (by OCT) at the baseline and Week 12 and 24 visits.
•The proportion of patients losing ≥ 0 letters on the ETDRS visual acuity chart from baseline at the Week 12 and 24 visits.
•The proportion of patients gaining ≥ 5 letters on the ETDRS visual acuity chart from baseline at the Week 12 and 24 visits.
•The proportion of patients gaining ≥ 10 letters on the ETDRS visual acuity chart from baseline at the Week 12 and 24 visits.
•The proportion of patients gaining ≥ 20 letters on the ETDRS visual acuity chart from baseline at the Week 12 and 24 visits.
•The proportion of patients gaining ≥ 25 letters on the ETDRS visual acuity chart from baseline at the Week 12 and 24 visits.
•The proportion of patients gaining ≥ 30 letters on the ETDRS visual acuity chart from baseline at the Week 12 and 24 visits.
•The proportion of patients who are 20/40 or better at the Week 12 and Week 24 visits. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Week 12 and week 24 visits. Please see E.5.2 for details. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Study drug is given by an unmasked 1st Investigator, 2nd Investigator is blinded to study drug |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| E10030 sham - sterile empty syringe without an attached needle |
|
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Austria |
| Belgium |
| Colombia |
| France |
| Germany |
| Hungary |
| Israel |
| Italy |
| Latvia |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last visit of the last subject. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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