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 choroidal neovascularization (CNV) |
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E.1.1.1 | Medical condition in easily understood language |
Impaired vision due to abnormal growth of blood vessels in the choroid which is caused by an intrinsic substance, so-called vascular endothelial growth factor (VEGF)
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060837 |
E.1.2 | Term | Choroidal neovascularization |
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 | 19.0 |
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 |
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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 intravitreal injection of 0.5 mg ranibizumab, administered based on individual patient needs has superior efficacy compared to sham treatment in adult patients with visual impairment due to VEGF-driven CNV other than wAMD and PM. The primary objective will be assessed by the best corrected visual acuity (BCVA) change from baseline to Month 2. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of ranibizumab as compared to sham treatment by assessing
• BCVA change over time to Month 2
• change in CSFT and CSFV (by OCT) from baseline (BL) over time to Month 2
• presence of intra-/sub-retinal fluid (by OCT) and presence of active chorioretinal leakage (by FA) at Month 2
To evaluate the efficacy of ranibizumab by original treatment assignment by assessing:
• average BCVA change from Month 1 to 6 from Month 1 to 12 compared to BL
• change from BL in CSFT and CSFV assessed by OCT by visit
• presence of intra-/subretinal fluid (by OCT) and presence of active chorioretinal leakage (by FA) at Month 2, 6 and 12 compared to BL
•proportion of patients with ≥ 1,≥ 5,≥ 10 and ≥ 15 letters gain or reaching 84 letters, at Month 2, 6 and 12
To assess the number of ranibizumab (re-)treatments by Month 2, 6 and 12
To evaluate the safety of ranibizumab as assessed by type, frequency and severity of
ocular and non-ocular AE up to months 2, 6 and 12
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E.2.3 | Trial contains a sub-study | No |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
To describe the efficacy and safety of ranibizumab in adolescent patients |
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E.3 | Principal inclusion criteria |
1. Diagnosis of treatment naïve active CNV secondary to any causes, except wAMD and PM in adults;
2. All types of CNV lesions present in the study eye;
3. BCVA must be between ≥ 24 and ≤ 83 letters in the study eye tested at 4 meters starting distance using ETDRS-like visual acuity charts;
4. Visual loss in the study eye should only be due to the presence of any eligible types of CNV based on ocular clinical, as well as FA and OCT images.
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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 CNV at screening;
5. Active diabetic retinopathy, active ocular/periocular infectious disease or active intraocular inflammation at screening
6. Confirmed intraocular pressure ≥ 25 mmHg for any reason at screening
7. Neovascularization of the iris or neovascular glaucoma at screening
8. CNV secondary to PM or wAMD
9. Use of any systemic anti-VEGF drugs within 6 months before baseline;
10. History of focal laser photocoagulation with involvement of the macular area
administered to treat CNV at any time;
11. History of intraocular treatment with any anti-angiogenic drugs or
verteporfin photodynamic therapy 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Best corrected visual acuity (BCVA) change from baseline to Month 2 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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 chorioretinal leakage assessed by FA at Month 2
5) Average BCVA change in study eye from baseline to Month 1 through Month 12
6) Change from baseline in CSFT and CSFV in study eye by visit
7) Presence of intra-/subretinal fluid in study eye at Month 2, Month 6 and Month 12 compared to Baseline
8) Presence of active chorioretinal leakage in study eye at Month 2, Month 6 and Month 12 compared to Baseline
9) Proportion of patients with ≥ 1, ≥ 5, ≥ 10 and ≥ 15 letters gain or reaching 84 letters in study eye, at Month 2, Month 6 and Month 12
10) Proportion of patients with > 1, > 5, > 10 and > 15 letters loss at Month 2, Month 6 and Month 12
11) Number of ranibizumab treatments and retreatments to study eye by Month 2, Month 6 and Month 12
12) Type, frequency and severity of ocular and non-ocular adverse events in the study eye up to Month 2, up to Month 6 and up to Month 12
13) Requirement for rescue treatment at Month 1
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 |
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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) |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 |
Brazil |
Canada |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Hong Kong |
Hungary |
India |
Italy |
Korea, Republic of |
Latvia |
Lithuania |
Peru |
Poland |
Portugal |
Russian Federation |
Singapore |
Slovakia |
South Africa |
Spain |
Switzerland |
Turkey |
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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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
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 |