E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Exudative 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 | 10015902 |
E.1.2 | Term | Exudative senile macular degeneration of retina |
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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 |
The objectives of this trial is to compare the safety and efficacy (best corrected ETDRS visual acuity) of Macugen® when given as intravitreous injections of 0.3mg/eye every 6 weeks plus sham PDT for up to 102 weeks to the same regimen of Macugen® plus PDT with Visudyne® and also to PDT with Visudyne® given on the same day as Macugen® if indicated, as often as every 12 weeks based on the presence of CNV leakage as indicated in the label, in subjects with predominantly classic subfoveal choroidal neovascularization (CNV) secondary to AMD. Primary endpoint to be assessed at 54 weeks. Overall health status and vision-related functional status will be measured using standardized subject reported outcomes questionnaires. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Ophthalmic Criteria 1. Subfoveal choroidal neovascularization (CNV) due to AMD. 2. Predominantly classic lesion composition. 3. Best corrected visual acuity in the study eye between 20/40 and 20/200, and better or equal to 20/800 in the fellow eye. 4. The greatest linear dimension of the lesion (including blood, neovascularization, and scar/atrophy) must be >5,400 microns and the most nasal part of the lesion must be at least 200 microns from the temporal edge of the optic disc. At least 50% of the total lesion size must be CNV (classic CNV plus any occult CNV). 5. The total area of any lesion components other than CNV, such as subretinal hemorrhage must comprise less than 50% of total lesion size. 6. Clear ocular media and adequate papillary dilatation to permit good quality stereoscopic fundus photography. 7. Intraocular pressure (IOP) of 21mmHg or less.
General Criteria 1. Subjects of either gender, aged ≥ 50 years. 2. Performance Status ≤ 2 according to Eastern Cooperative Oncology Group (ECOG) / World Health Organization (WHO) scale. 3. Normal electrocardiogram (ECG) or clinically non-significant changes. 4. Women must 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. 5. Adequate haematological function: haemoglobin ≥10g/dL; platelet count ≥ 130 x 109/L; WBC ≥ 3.8 x 109/L. 6. Adequate renal function: serum creatinine ≤ 2.5 mg/dl and BUN within 2 x the upper limit of normal (ULN). 7. Adequate liver function: serum bilirubin ≤ 1.5 mg/dl, GGT, SGOT/ALT, SGPT/AST, and alkaline phosphatase within 2 x ULN. 8. Provide written informed consent. 9. Ability to return for all trial visits. |
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E.4 | Principal exclusion criteria |
Subjects will not be eligible for the trial if patients cannot attend all study required visits, or if any of the following criteria are present systemically or in the study eye: 1. Previous subfoveal and non foveal thermal laser therapy. 2. Any prior PDT with Visudyne® to the study eye. 3. More than 25% of the total lesion size made up of scarring or atrophy. Subjects with subfoveal scar or subfoveal atrophy are excluded. 4. Significant media opacities, including cataract, which might interfere with visual acuity, assessment of toxicity, or fundus photography. Subjects should not be entered if there is likelihood that they will require cataract surgery within the following 2 years. 5. Presence of other causes of choroidal neovascularixzation, including pathologic myopia (spherical equivalent of –8 diopters or more negative, or axial length of 25mm or more), the ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, and multifocal choroiditis. 6. Any intraocular surgery or thermal laser to the study eye within 3 months of trial entry. 7. Any ocular or peri-ocular infection in the past 4 weeks. 8. Previous posterior vitectomy. 9. Previous or concomitant therapy with intravitreous corticosteroids. 10. Previous or concomitant therapy with another investigational agent to treat AMD, except oral supplements of vitamins and minerals. 11. Presence of pigment epithelia tears or rips. 12. Any of the following underlying diseases including: - Diabetic retinopathy - History or evidence of severe cardiac disease (e.g. NYHA Functional Class III or IV) clinical or medical history of unstable angina, actute coronary syndrome, myocardial infarction or revascularization with 6 months, ventricular tachyarrythmias requiring ongoing treatment. - History or evidence clinically significant peripheral vascular disease, such as intermittent claudication or prior amputation. - Clinically significant impaired renal (serum creatinine >2.5mg/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 study entry. 13. Previous therapeutic radiation in the region of the study eye. 14. Any treatment with an investigational agent in the past 60 days for any condition. 15. Known serious allergies to the fluorescein dye used in angiography, contraindications indicated in the product label for Visudyne® / PDT (porphyria), or to the components of Macugen® formulation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is vision at 54 weeks based on comparing the proportion of subjects having lost <15 letters of visual acuity (defined as responders). Secondary efficacy endpoints to be measured at 54 weeks include: the proportion of subjects gaining ≥ 0, 5, 10, and 15 letters of visual acuity; the proportion of subjects having lost ≥ 30 letters of visual acuity; the number of PDT treatments required; proportion of subjects who reach ≥ 20/200; and the mean change in visual acuity. The same endpoints will be measured at 102 weeks.
In addition to the primary and secondary efficacy endpoints, additional efficacy data are collected. These endpoints will include: changes in lesion size; CNV progression; CNV size; retinal thickness (OCT) at the center of the fovea; and changes in subject reported vision-related functioning and preference values (NEI VFQ-25 and SST VPVS).
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Sham Photodynamic Therapy with 5% dextrose |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
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 | 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
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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 | |
E.8.9.1 | In the Member State concerned months | 54 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 54 |