E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060837 |
E.1.2 | Term | Choroidal neovascularization |
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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 |
•Demonstrate that Visudyne® combination therapy is not inferior to Lucentis™ monotherapy with respect to the mean change from baseline in Best-Corrected Visual Acuity (BCVA) (letters) at Month 12. • Evaluate the proportion of patients with a treatment-free interval of at least 3 months duration at any timepoint following Month 2.
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E.2.2 | Secondary objectives of the trial |
• Demonstrate that Visudyne® combination therapy is superior to Lucentis™ monotherapy, based on the number of Lucentis™ retreatments administered over 9 months following the Month 2 treatment. • Evaluate the time to first retreatment of Lucentis™ by comparing Visudyne® combination therapy with Lucentis™ monotherapy following the Month 2 Lucentis™ treatment • Assess the safety of Visudyne® combination therapy compared to Lucentis™ monotherapy as assessed by ophthalmic and vital signs evaluations and adverse AE reports over 12 months • Evaluate the efficacy of Visudyne® combination therapy compared to Lucentis™ monotherapy on BCVA changes from baseline as assessed by ETDRS charts and VA protocol over 12 months • Evaluate the efficacy of Visudyne® combination therapy compared to Lucentis™ monotherapy on changes in angiographic and OCT outcomes from baseline over 12 months • Assess the mean change from baseline in BCVA at Months 1, 2 and 3 to evaluate the onset of effect |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female patients of any race 50 years or older • Primary or recurrent active subfoveal CNV secondary to AMD, including those with predominantly classic, minimally classic or occult lesions with no classic component • The total area of CNV (including both classic and occult components) encompassed within the lesion must be > 50% of the total lesion area as defined by fluorescein angiography (FA) • The total lesion are must have the Greatest Linear Dimension (GLD) ≤ 5400 microns (~9 MPS Disc Areas [DA]) • If the lesion is classified as occult with no classic CNV component, the lesion must have evidence of recent disease progression as defined in the study glossary under “active lesion” • BCVA letter score in the study eye between 73-24 (approximately 20/40 to 20/320 Snellen equivalent) using an ETDRS chart measured at 4 meters distance • Patients who provide written and informed consent according to legal requirements, and who have signed the consent form prior to initiation of any study procedure • Patients willing and able to comply with all study procedures
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E.4 | Principal exclusion criteria |
Ocular concomitant conditions/ diseases • Presence of angioid streaks, presumed ocular histoplasmosis syndrome, pathologic myopia (-8 or more with evidence of posterior segment abnormalities consistent with pathologic myopia), or CNV secondary to causes other than AMD • Presence of fibrosis, hemorrhage, pigment epithelial detachments, or other hypofluorescent lesions obscuring greater than 50% of the CNV lesion • Tear (rip) of the retinal pigment epithelium • Active, or history of, ocular inflammation or infection in the study eye within 30 days prior to Screening • Uncontrolled glaucoma in the study eye (defined as intraocular pressure, IOP ≥ 25 mmHg despite treatment with two or more topical pharmacological anti-glaucomatous medication) • Any concurrent ocular condition in the study eye that may result in visual loss during the study Ocular treatments • Prior Visudyne®, external-beam radiation, subfoveal focal laser photocoagulation, submacular surgery, or transpupillary thermotherapy in the study eye • Prior treatment with Macugen®, Lucentis™, Avastin [bevacizumab] or other anti-angiogenic compound or any investigational treatment (e.g. Ruboxistaurin, Retaane [anecortave acetate], squalamine, siRNA, VEGF-Trap etc.) for neovascular AMD in the study eye (treatment of thefellow eye is permitted if administered > 30 days before Screening) • History of intraocular surgery in the study eye including pars plana vitrectomy, except for uncomplicated cataract surgery more than 60 days prior to screening • History of YAG laser posterior capsulotomy in the study eye within 30 days prior to screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
The two primary efficacy variables are • mean change from baseline in best corrected visual acuity (BCVA) at month 12 • the proportion of patients with a treatment-free interval of at least 3 months duration at any timepoint following Month 2 The primary analysis will be performed on the ITT population using the LOCF approach for imputing missing data |
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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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Assessment of patients treatment satisfaction and treatment preferences. |
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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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 37 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |