E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male and female patients ≥50 years of age with either with predominantly classic, minimally classic, or occult lesions with no classic component, all with primary or recurrent subfoveal CNV secondary to 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 |
The primary objective is to demonstrate the non-inferiority of two dosing regimens of ranibizumab administered as three consecutive monthly injections followed by quarterly injections (alternative dosing) compared to ranibizumab administered monthly (monthly dosing) as determined by the mean change in best-correct visual acuity (BCVA) from Baseline to Month 12 as assessed with ETDRS-like VA charts at an initial distance of four meters. |
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives: 1. To evaluate the safety and tolerability of alternative dosing versus monthly dosing by comparing rates of adverse events and serious adverse events, as well as changes in laboratory values and vital signs at Month 12 and 24. 2. To evaluate the effects of alternative dosing versus monthly dosing in the change in visual function and on retinal structure at Month 12 and 24.
Exploratory objectives: 1. To explore the effects of alternative dosing versus monthly dosing on peripheral visual function at Month 12 and 24 as assessed by contrast sensitivity and reading performance. 2. To explore the effects of alternative dosing versus monthly dosing on lesion growth at Month 12 and 24 as assessed by retinal function measurements quantified with microperimetry at selected study sites.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male or female patients 50 years of age or greater. 2. Patients with primary or recurrent subfoveal CNV secondary to AMD, including those with predominantly classic, minimally classic or occult lesions with no classic component. 3. The total area of CNV (including both classic and occult components) encompassed within the lesion must be ³ 50% of the total lesion area. 4. The total lesion area ≤ 12 disc areas for minimally classic or occult with no classic component and ≤ 9 disc areas (5400µm) in greatest linear dimension with predominately classic lesions. 5. Patients who have a BCVA score between 73 and 24 letters (approximately 20/40 to 20/320), inclusively, in the study eye. 6. Willing and able to give written informed consent according to legal requirements, and who have signed the consent form prior to initiation of any study procedure. 7. Willing and able to comply with all study procedures. |
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E.4 | Principal exclusion criteria |
1. Prior treatment in the study eye with verteporfin, external-beam radiation therapy, subfoveal focal laser photocoagulation, vitrectomy, or transpupillary thermotherapy. 2. History of submacular surgery or other surgical intervention for AMD in the study eye, glaucoma filtration surgery, corneal transplant surgery. 3. Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within one month preceding Baseline. 4. Patients with angioid streaks or precursors of CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia. 5. Extracapsular extraction of cataract with phacoemulsification within three months preceding Baseline, or a history of post-operative complications within the last 12 months preceding Baseline in the study eye (uveitis, cyclitis, etc.). 6. History of uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma medication). 7. Aphakia with absence of the posterior capsule in the study eye. 8. Active intraocular inflammation (grade trace or above) in the study eye. 9. Any active infection involving ocular adnexa including infectious conjunctivitis, keratitis, scleritis, endophthalmitis, as well as idiopathic or autoimmune-associated uveitis in either eye. 10. Vitreous hemorrhage or history of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye. 11. Presence of a retinal pigment epithelial tear involving the macula in the study eye. 12. Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either ³ 50% of the total lesion area or ³ 1 disc area in size. 13. Subfoveal fibrosis or atrophy in the study eye. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to demonstrate the non-inferiority of two alternative dosing regimens of ranibizumab versus monthly dosing of ranibizumab as determined by the mean change in best-corrected visual acuity (BCVA) from Baseline to Month 12 as assessed with ETDRS-like VA charts at an initial distance of four meters. This will be achieved by demonstrating that at least one alternative dosing regimen of ranibizumab (0.3 mg or 0.5 mg) is non-inferior to ranibizumab (0.3 mg) administered monthly. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
0.3 mg ranibizumab (active control) |
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E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | 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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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 |