E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Visual impairment due to vascular endothelial growth factor (VEGF)
driven macular edema (ME) |
|
E.1.1.1 | Medical condition in easily understood language |
Impaired vision due to increased accumulation of fluid in the back of the eye (macula) caused by an intrinsic substance, so-called vascular endothelial growth factor (VEGF) |
|
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 | 18.0 |
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 | 18.0 |
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 |
To demonstrate that an individualized regimen of intravitreal injection of
0.5 mg ranibizumab has superior efficacy compared to sham treatment
in adult patients with visual impairment due to VEGF-driven ME.
The primary objective will be assessed by the BCVA change from
baseline to Month 2. |
|
E.2.2 | Secondary objectives of the trial |
Evaluate efficacy of ranibizumab vs sham treatment by assessing
•BCVA change from baseline (BL) by visit to Mo 2
•change in CSFT and CSFV (by OCT) from BL over time to Mo 2
•presence of intra-/sub-retinal fluid (by OCT) and presence of active ME leakage (by FA) at Mo 2
•rescue treatment requirement at Mo 1
Evaluate efficacy of ranibizumab by original treatment assignment by assessing
•average BCVA change from BL to Mo 1 through 12
•change from BL in CSFT and CSFV (by OCT) by visit
•presence of intra-/sub-retinal fluid (by OCT) and presence of active ME leakage (by FA) at Mo 2,6 and 12 compared to BL
•proportion of patients with ≥1, ≥5, ≥10 and ≥15 letters gain or reaching 84 letters, at Mo 2, 6 and 12
•proportion of patients with >1, >5,>10 and >15 letters loss at Mo 2,6 and 12
Assess number of ranibizumab (re)treatments by Mo 2,6 and 12
Evaluate:
•safety of ranibizumab (ocular and non-ocular AE) vs sham at Mo 2 and over time at Mo 6 and 12
•reasons for treatment decision |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of treatment naïve (patient has not received any prior medication/ treatment for the ME lesion under study) active ME secondary to any causes (for adult patients: except DME and RVO);
2. BCVA must be between ≥ 24 and ≤ 83 letters tested at 4 meters starting distance using ETDRS-like visual acuity charts;
3. Visual loss should be only due to the presence of any eligible types of ME based on ocular clinical, as well as FA and OCT findings.
|
|
E.4 | Principal exclusion criteria |
1. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment;
2. History of malignancy of any organ system within the past 5 years;
3. History of stroke less than 6 months prior to screening;
4. Active systemic inflammation or infection, related directly to the underlying causal disease of ME at screening;
5. Active diabetic retinopathy, active ocular/periocular infectious disease or active intraocular inflammation at screening;
6. Confirmed intraocular pressure (IOP) ≥ 25 mmHg for any reason at screening;
7. Neovascularization of the iris or neovascular glaucoma at screening;
8. ME secondary to DME or RVO (for adult patients only);
9. Use of any systemic anti-VEGF drugs within 6 months before baseline;
10. History of focal/grid laser photocoagulation with involvement of the macular area administered to treat ME at any time;
11. History of intraocular treatment with any anti-angiogenic drugs (including any anti-VEGF agents) or verteporfin photodynamic therapy
(vPDT) at any time; 12. History of intravitreal treatment with corticosteroids at any time;
13. History of vitreoretinal surgery at any time. Other protocol-defined inclusion/exclusion criteria may apply. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Best corrected visual acuity (BCVA) change from baseline to Month 2 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1) BCVA change from baseline by visit up to Month 2 in study eye (ranibizumab as compared to sham treatment)
2) Change in central subfield thickness (CSFT) and central subfield
volume (CSFV) in study eye from baseline over time to
Month 2
3) Presence of intra-/subretinal fluid in study eye at Month 2
4) Presence of active ME leakage assessed by fluorescein angiography
(FA) at Month 2
5) Requirement for rescue treatment at Month 1
6) Average BCVA change in study eye from baseline to Month 1 through
Month 12
7) Change from baseline in CSFT and CSFV in study eye by visit
8) Presence of intra-/subretinal fluid in study eye at Month 2, Month 6,
and Month 12 compared to Baseline
9) Presence of active ME leakage in study eye at Month 2, Month 6, and
Mon th 12 compared to Baseline
10) Proportion of patients with 1 ≥ 5≥ 10 ≥ and 15 ≥ letters gain or
reaching 84 letters, at Month 2, Month 6 and
Month 12
11) Proportion of patients with > 1, > 5, > 10 and > 15 letters loss at
Month 2, Month 6 and Month 12
12) Number of ranibizumab treatments and retreatments to study eye by
Month 2, Month and Month 12
13) Type, frequency and severity of ocular and non-ocular adverse
events in the study eye up Month 2, up to
Month 6 and up to Month 12 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.8.1.7.1 | Other trial design description |
open label group for adolescents |
|
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 |
sham injection (adults only) |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Information not present in EudraCT |
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 | 49 |
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 |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Ireland |
Israel |
Italy |
Korea, Republic of |
Latvia |
Netherlands |
Russian Federation |
Singapore |
Slovakia |
South Africa |
Spain |
Switzerland |
Turkey |
United Kingdom |
|
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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |