| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Exudative age-related macular degeneration |
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| MedDRA Classification |
| 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 |
This study is designed to evaluate the safety and efficacy of 1.25mg dose of Avastin® given by intravitreous injection in improving visual acuity in patients with subfoveal choroidal neovascularisation secondary to age-related macular degeneration.
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| E.2.2 | Secondary objectives of the trial |
Secondary Objective
1. The proportion of subjects who lose fewer than 15 letters (approximately 3 lines) ad the proportion who have gained 5 letters or more in the best corrected visual acuity score at 12 months compared with baseline, based on the ETDRS visual acuity chart and assessment at a starting distance of 4m.
2. To evaluate the safety and tolerability of intravitreal injections of Avastin® given every 6 weeks.
3. Mean change in central OCT retinal thickness
4. If study is continued after the analysis of data at 12 month time point then after the second treatment year of the study, the same objectives will be analyzed on unmasked data.
Safety Outcome Measures
Incidence and severity of ocular adverse events
Incidence and severity of non-ocular adverse events
Changes and abnormalities in clinical laboratory parameters
Changes in vital signs
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
• Age >50 years
• Primary subfoveal CNV lesions secondary to AMD in the study eye
• An occult lesion must have presumed evidence of disease progression, defined as; deterioration of best corrected vision by 1 Snellen line or 5 letters on ETDRS chart within the past 3 months due to progression of CNV, and one or more of the following- 1. Presence of sub or intraretinal blood 2. Growth of lesion size on the angiogram by more than 10% in the past 3 months 3. Increase in OCT thickness by > 250 microns by OCT
• Total lesion size < 12 disc areas including all contiguous lesion components
• Area of fibrosis <25% of the total lesion area
• Area of subretinal blood less than 50% of total lesion area
• Best corrected visual acuity, using ETDRS charts, of 20/40 to 20/320 (Snellen equivalent) in the study eye |
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| E.4 | Principal exclusion criteria |
• Prior treatment with external-beam radiation therapy, transpupillary thermotherapy (TTT). thermal laser, or verteporfin therapy in the study eye
• Treatment with verteporfin in the non-study eye less than 7 days preceding Day 0,
• Previous participation in a clinical trial (for either eye) involving anti-angiogenic drugs (Macugen® , Avastin® , anecortave acetate, protein kinase C inhibitors, etc.)
• Previous intravitreal drug delivery (e.g. intravitreal corticosteroid injection or device implantation) in the study eye
• History of vitrectomy surgery in the study eye
• History of greater than mild non-proliferative diabetic retinopathy or any diabetic maculopathy
• History of retinal vascular occlusions
• History of glaucoma filtering surgery in the study eye
• History of corneal transplant in the study eye
• History of submacular surgery or other surgical intervention for AMD in the study eye
• Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals)
• Current or intending use of warfarin or known abnormal blood clotting
Lesion Characteristics
• Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either >50% of the total lesion area| or >1 DA in size I
• Subfoveal fibrosis or atrophy in the study eye.
• CNV in either eye due to causes other than AMD, such as ocular histoplasmosis, | trauma, or pathologic myopia
• Retinal pigment epithelial tear involving the macula in the study eye
Concurrent Ocular Conditions
• Any concurrent intraocular condition in the study eye (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, could either require medical or surgical intervention during the 24-month study period to prevent or treat visual loss that might result from that condition, or if allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of best corrected visual acuity over the 24-month study period
• Active intraocular inflammation (grade trace or above) in the study eye
• Current vitreous hemorrhage in the study eye
• History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4} in the study eye
• History of idiopathic or autoimmune-associated uveitis in either eye
• Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
• Aphakia or absence of the posterior capsule in the study eye
Previous violation of the posterior capsule in the study eye is also excluded unless it occurred as a result of YAG posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation.
• Spherical equivalent of the refractive error in the study eye demonstrating more than -8 diopters of myopia or signs of pathologic myopia with a refraction of 4-8 diopters
For subjects who have undergone prior refractive or cataract surgery in the study eye, the preoperative refractive error in the study eye cannot exceed -8 diopters of myopia.
• Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Day 0
• Uncontrolled glaucoma in the study eye (defined as intraocular pressure >30 mmHg despite treatment with anti-glaucoma medication)
Concurrent Systemic Conditions
• Premenopausal women not using adequate contraception
The following are considered effective means of contraception: surgical sterilization; use of oral contraceptives; barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel; an IUD; or contraceptive hormone implant or patch.
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications
• Current treatment for active systemic infection
• Recent stroke, or cardiac event, uncontrolled angina or hypertension.
Other
• History of allergy to fluorescein
• Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded by the central reading center
• Inability to comply with study or follow-up procedures
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the proportion of subjects who gain more than 15 letters (approximately 3 lines) of best corrected visual acuity score at the 12 month time point compared with baseline, based on the ETDRS visual acuity chart and assessment at a starting distance of 4m. |
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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 | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 | No |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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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| Trial ends when the last recruited patients completes their 1 year follow up visit |
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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 |
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