E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
visual impairment due to macular edema secondary to central retinal vein occlusion (CRVO) |
|
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 | LLT |
E.1.2 | Classification code | 10007972 |
E.1.2 | Term | Central retinal vein occlusion |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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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 | 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 evaluate the efficacy of an individualized stabilization criteria-driven
PRN dosing regimen with 0.5 mg ranibizumab as assessed by the mean BCVA change
at Month 12 compared to Baseline. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of PRN dosing of 0.5-mg ranibizumab injections as assessed by:
• the mean change in BCVA
• the mean average change in BCVA
• the proportion of patients achieving:
- BCVA improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 letters
- reaching BCVA values of ≥73 letters (approximate 20/40 Snellen chart equivalent)
- with a BCVA loss of <15 letters
• the mean change in central reading center (CRC)-assessed central subfield thickness (CSFT)
• the patient-reported outcomes by the NEI-VFQ-25 composite score and subscales
To evaluate the mean average change in BCVA from the timepoint of the first treatment interruption (if due to BCVA stabilization)
To evaluate the mean change in BCVA by visit from the timepoint of the first treatment interruption (if due to BCVA stabilization)
To evaluate the safety of ranibizumab injections as assessed by the type, frequency, and severity of ocular and non-ocular AEs |
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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 must be at least 18 years of age
- Diagnosis of visual impairment exclusively due to ME secondary to central retinal vein occlusion (CRVO)
- Best-corrected visual acuity at Screening and Baseline must be between 73 and 19 letters Early Treatment Diabetic Retinopathy Study (ETDRS), inclusively (approximate Snellen chart equivalent of 20/40 and 20/400)
Other protocol-defined inclusion criteria may apply |
|
E.4 | Principal exclusion criteria |
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
• Stroke or myocardial infarction less than 3 months prior to 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 has to 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 on medication or according to investigator’s judgment) at Screening or Baseline or diagnosed within 6 months prior to Baseline in either eye
• Neovascularization of the iris or neovascular glaucoma in either eye
• Use of any systemic anti-vascular endothelial growth factor (VEGF) drugs within 6 months prior to Baseline (eg, sorafenib [Nexavar®], sunitinib [Sutent®], bevacizumab [Avastin®])
• Prior treatment with any anti-angiogenic drugs (including any anti-VEGF agents) within 3 months prior to Baseline in either eye (eg, pegaptanib [Macugen®], ranibizumab [Lucentis®], bevacizumab [Avastin®])
• Panretinal laser photocoagulation within 3 months prior to Baseline or anticipated or scheduled within the next 3 months following Baseline in the study eye
• Focal or grid laser photocoagulation within 4 months prior to Baseline in the study eye
• Use of intra- or periocular corticosteroids (including sub-Tenon) within 3 months prior to Screening in the study eye
• Any use of intraocular corticosteroid implants (eg, dexamethasone [Ozurdex®], fluocinolone acetonide [Iluvien®]) in the study eye
Other protocol-defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the mean change in BCVA at Month 12 compared to
Baseline. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
at Month 12 compared to Baseline. |
|
E.5.2 | Secondary end point(s) |
The following secondary efficacy endpoints will be evaluated for the study eye:
• the mean change in BCVA from Month 1 through Month 24 compared to Baseline, by visit
• the mean change in BCVA from Month the timepoint of the first treatment interruption (due to BCVA stabilization) through Month 24, by visit
• the mean average change in BCVA from Month 1 through Month 12 and from Month 1 through Month 24 compared to Baseline
• the mean average change in BCVA from the timepoint of the first treatment interruption (due to BCVA stabilization) through Month 12 and/or Month 24
• the number and proportion of patients with a BCVA improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 letters from Baseline to Month 12 and Month 24, by visit
• the number and proportion of patients with a BCVA value of ≥73 letters (approximate 20/40 Snellen chart equivalent) at Month 12 and Month 24, by visit
• the number and proportion of patients with a BCVA loss of <15 letters from Baseline up to Month 12 and Month 24, by visit
• the mean change in CRC-assessed CSFT from Month 1 through Month 12 and Month 24 compared to Baseline
• the mean change in patient-reported outcomes in NEI-VFQ-25 score (composite score and subscales) at Month 12 and Month 24 compared to Baseline |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
from Month 1 through Month 12 and from Month 1 through Month 24 compared to Baseline
|
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | No |
E.8.2.2 | Placebo | No |
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.8.5 | 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 |