E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
visual impairment due to macular edema secondary to branch retinal occlusion (BRVO) |
|
E.1.1.1 | Medical condition in easily understood language |
visual impairment caused by occluded vessels (veins) that lead to swelling of the retina in the back of the eye |
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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 | PT |
E.1.2 | Classification code | 10025415 |
E.1.2 | Term | Macular oedema |
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 | 10038907 |
E.1.2 | Term | Retinal vein occlusion |
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 | 10047571 |
E.1.2 | Term | Visual impairment |
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 primary objective is to demonstrate that an individualized stabilization-criteria-driven PRN dosing regimen (PRN) with 0.5-mg ranibizumab administered with or without adjunctive laser treatment has superior efficacy as compared to the current standard of care, laser photocoagulation, in patients with visual impairment due to ME secondary to BRVO. The primary objective will be assessed by the mean BCVA change at Month 6 compared to Baseline. |
|
E.2.2 | Secondary objectives of the trial |
To demonstrate in a first step that treatment with ranibizumab with adjunctive laser is noninferior
to treatment with ranibizumab monotherapy as assessed by the mean average BCVA change from Month 1 through Month 24 compared to Baseline. To demonstrate in a second step (after demonstrating non-inferiority) that ranibizumab with adjunctive laser reduces the number of ranibizumab retreatments as compared to ranibizumab monotherapy by assessing the number of ranibizumab treatments applied up to Month 23. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent must be obtained before any study assessment is
performed
• Male or female patients ≥18 years of age
• Diagnosis of visual impairment exclusively due to ME secondary to BRVO
• BCVA score at Screening and Baseline between 73 and 19 letters Early
Treatment Diabetic Retinopathy Study (ETDRS), inclusively (approximate Snellen
chart equivalent of 20/40 and 20/400) |
|
E.4 | Principal exclusion criteria |
• Pregnant or nursing (lactating) women
• Stroke or myocardial infarction less than 3 months before Screening
• Uncontrolled blood pressure defined as systolic value of >160 mm Hg or diastolic value of >100 mm Hg at Screening or Baseline. Antihypertensive treatment can be initiated and must be taken for at least 30 days after which the patient can be assessed for study eligibility a second time
• Any active periocular or ocular infection or inflammation (eg, blepharitis, conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) at Screening or Baseline in either eye
• Uncontrolled glaucoma (intraocular pressure [IOP] ≥30 mm Hg while on medication or according to investigator’s judgment) at Screening or Baseline or diagnosed within 6 months before Baseline in either eye
• Neovascularization of the iris or neovascular glaucoma in the study eye
• Use of any systemic antivascular endothelial growth factor (anti-VEGF) drugs within 6 months before Baseline (eg, sorafenib [Nexavar®], sunitinib [Sutent®], bevacizumab [Avastin®])
• Treatment (or anticipated treatment in the fellow eye for non-RVO indications during the study) with any anti-angiogenic drugs (including any anti-VEGF agents) within 3 months before Baseline in either eye (eg, pegaptanib [Macugen®], ranibizumab [Lucentis®], bevacizumab [Avastin®])
• Panretinal laser photocoagulation within 3 months before Baseline or anticipated or scheduled within the next 3 months following Baseline in the study eye
• Focal or grid laser photocoagulation within 4 months before Baseline in the study eye
• Use of intra- or periocular corticosteroids (including sub-Tenon) within 3 months before Screening in the study eye
• Any use of intraocular corticosteroid implants (eg, dexamethasone [Ozurdex®], fluocinolone acetonide [Iluvien®]) in the study eye |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable is the mean BCVA change at Month 6 compared to Baseline in patients with visual impairment due to ME secondary to BRVO. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• The mean average change in BCVA from Month 1 through Month 24 compared to Baseline
• The number of ranibizumab treatments
• The mean average change in BCVA from Month 1 through Month 6 compared to Baseline
• The mean change in BCVA from Baseline up to Month 12 and Month 24, by visit
• The mean average change in BCVA from the time point of the first treatment interruption (due to BCVA stabilization) for all following visits until End of Study
• The mean change in BCVA from the time point of the first treatment interruption (due to BCVA stabilization) assessed on a monthly basis until End of Study
• The number and proportion of patients with a BCVA gain of ≥1, ≥5, ≥10, ≥15, and ≥30 letters / loss of <15 letters from Baseline up to Month 6 and Month 24, by visit
• The number and proportion of patients with a BCVA value ≥73 letters (20/40 Snellen equivalent) from Baseline up to Month 6 and Month 24, by visit
• The mean average BCVA change from the time point of first ranibizumab treatment for all following visits until End of Study in patients randomized to laser
• The mean change in CRC-assessed CSFT from Baseline up to Month 6 and Month 24, by visit
• The mean change in patient reported outcomes in NEI-VFQ-25 score (composite score
and subscales) at Month 6 and Month 24 compared to Baseline |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
From Month 1 through Month 24 |
|
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
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 |
|
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
Denmark |
France |
Greece |
Hungary |
Ireland |
Italy |
Netherlands |
Norway |
Poland |
Portugal |
Slovakia |
Spain |
Sweden |
Switzerland |
Turkey |
United Kingdom |
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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
|
|
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 | 8 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 20 |