E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Visual impairment due to choroidal neovascularization secondary to pathologic myopia |
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E.1.1.1 | Medical condition in easily understood language |
Visual impairment due to choroidal neovascularization secondary to
pathologic myopia |
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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 | 10036803 |
E.1.2 | Term | Progressive high (degenerative) myopia |
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 | 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 | 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 |
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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 the superior efficacy of 0.5 mg ranibizumab driven by stabilization criteria and/or by disease activity re-treatment criteria vs. vPDT (verteporfin Photodynamic Therapy) as assessed by the difference between the average level of best corrected visual acuity (BCVA) (letters) over all monthly post-baseline assessments from Month 1 to Month 3 and the baseline level of BCVA. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate non-inferiority of 0.5 mg ranibizumab intravitreal injections driven by disease activity re-treatment criteria versus 0.5 mg ranibizumab intravitreal injections driven by stabilization criteria as assessed by the difference between the average level of BCVA (letters) over all monthly post-baseline assessments from Month 1 to Month 6 and the baseline level of BCVA . |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or Female patients ≥ 18 years of age
2. Written informed consent given before any study related procedure is performed
3. Diagnosis of active CNV secondary to PM confirmed by complete ocular examination in the study eye using the following criteria:
• Presence of high myopia greater than -6D of spherical equivalence
• Ocular ultrasonography or biometry demonstrating anterio-posterior elongation measurement greater than or equal to 26 mm
• Presence of posterior changes compatible with the pathologic myopia (any signs of attenuation of Retinal pigment epithelium (RPE) and choroids, mottling of the RPE, tilted disc, geographic atrophy of RPE, Fuchs spots, posterior staphyloma, submacular hemorrhage, lacquer cracks) seen by fundus ophthalmoscopy and fundus photography
• Presence of active leakage from CNV seen by fluorescein angiography (FA)
• Presence of intra or subretinal fluid; or increase of central retinal thickness (CRT) seen by Optical coherence tomography (OCT)
4. At least one of the following lesion types is present in the study eye:
• subfoveal (presence of anormal neovasculature in the avascular central fovea)
• juxtafoveal (presence of abnormal neovasculature not under the center of the fovea but less than 200 μ from the center) with involvement of the central macular area
• extrafoveal (presence of abnormal neovasculature more than 200 µ from the center of the fovea) with involvement of the central macular area
• margin of the optic disc (presence of abnormal neovasculature at peripapilar area) with involvement of the central macular area
5. BCVA ≥ 24 letters and ≤ 78 and letters tested at 4 meters starting distance using ETDRS-like visual acuity chart (approximate 20/32 to 20/320 to Snellen chart)
6. Visual loss must be only due to the presence of any eligible types of CNV related to PM based on clinical ocular findings (described at inclusion criteria of the study eye), FA and OCT. (Also patients that have for example 20/60 as their best visual acuity due to PM, and they have additional vision loss, can be included)
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E.4 | Principal exclusion criteria |
• Patients with inability to comply with the study or follow procedures
• Presence of confirmed systolic blood pressure > 150 mmHg or diastolic > 90 mmHg at the time of enrollment
• History of stroke
• Any type of advanced, severe or unstable disease or it`s treatment, that could interfere with primary and/or secondary outcome evaluations including any medical condition that could be expected to progress, recur, or change to such an extend that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk
• Presence of active infectious disease or intra-ocular inflammation, active or suspected periocular infection in either eye at the time of enrollment
• Ocular disorders in the study eye that may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the 12-month study period (including retinal detachment, cataract and pre-retinal membrane of the macula)
• Presence of amblyopia or ocular disorders with final best corrected vision <20/200 or amaurosis in the fellow eye
• History of pan-retinal or focal/grid laser photocoagulation with involvement of the macular area in the study eye at any time
• History of intraocular treatment with any anti-vascular endothelial growth factor (VEGF) or vPDT at any time in the study eye
• History of intravitreal treatment with corticosteroids within 3 months prior to randomization in the study eye
• History of intra-ocular surgery within 3 months prior to the randomization in the study eye.
• History or presence of porphyria (as contraindication to Visudyne)
• Pregnant or nursing (lactating) women and Women of child-bearing potential. Women of child-bearing potential, defined as all woman physiologically capable of becoming pregnant, UNLESS they are: a) post-menopausal, or b) surgically sterile, or childbearing potential and use one or more reliable contarception methods.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the difference between the average level
of BCVA (letters) over all monthly post-baseline assessments from
Month 1 to Month 3 (endpoint) and the baseline level of BCVA. |
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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) |
- Difference between the average level of BCVA (letters) over all monthly
post-baseline assessments from Month 1 to Month 6 and the baseline
level of BCVA.
- Average level of BCVA (letters) over all monthly post-baseline
assessments from Month 1 to Month 12 and the baseline level of BCVA
and based on the time course of BCVA changes from baseline
- Compare the proportion of patients with ≥10 and ≥15 letters gain or
reaching 84 letters, and ≥10 and ≥15 letters loss for each month
between treatment groups
- Compare the proportion of patients with presence of active leakage
over time up to Month 12 in the treatment groups
- Number, severity, and relationship to the study drug of the Adverse
events as measure of safety and tolerability of 0.5 mg ranibizumab (two
regimens) vs. vPDT at Month 3, Month 6 and Month 12. |
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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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 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 | 50 |
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 |
Austria |
Canada |
France |
Germany |
Hong Kong |
Hungary |
India |
Italy |
Japan |
Korea, Republic of |
Latvia |
Poland |
Portugal |
Slovakia |
Spain |
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
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Provided in the protocol. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 14 |