E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
therapy of diabetic macular edema |
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E.1.1.1 | Medical condition in easily understood language |
therapy of diabetic macular edema |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
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 |
number of injections of study drug during the first year of treatment
mean change from baseline in BCVA at month 12
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E.2.2 | Secondary objectives of the trial |
• Proportion of patients with a vision acuity loss of fewer than 15 letters at month 12 (visit 13) compared with baseline • Proportion of patients with a vision acuity loss of more than 15 letters at month 12 (visit 13) compared with baseline • Proportion of patients with a treatment-free interval of at least 3 months duration at any time point following visit 3 • Drop out rates • Rate of non-responders • Retinal lesions • Changes in retinal thickness from baseline at month 4 and 12 (visit 13) • AEs
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients aged 18 years and older
Diabetes mellitus type 2 (insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM))
Clinical significant diabetic macular edema (diffuse or focal)
Visual acuity (decimal) reduced by diabetic macular edema to ≤ 0,3 and ≥ 0,05 (LogMar ≤ 1,3 and ≥ 0,5) stated by EDTRS charts.
The investigator has to be clinically convinced about vitrectomy might be beneficial and appropriate for the patient enrolled.
Signed informed consent
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E.4 | Principal exclusion criteria |
The investigator is clinically not convinced about vitrectomy being indicated or the possible side effects outweigh the possible positive effects of vitrectomy
Diabetes mellitus type 1
Visual acuity of the study eye (decimal) > 0,3 (LogMar < 0,5)
Visual acuity of the study eye (decimal) < 0,05 (LogMar > 1,3)
Central retinal thickness stated by SD-OCT < 250 µm
Any clouding of optical media influencing the evaluation of the retina
Previous focal laser coagulation of the macula in the study eye within 3 months prior to baseline
Previous treatment of diabetic macular edema involving intravitreal steroids or VEGF blockers within 6 months prior to baseline
Previous vitrectomy in the study eye
Previous cataract surgery in the study eye within 6 months prior to baseline
Pseudophakia with opening of the posterior capsule by surgery or YAG laser capsulotomy prior to baseline
History of glaucoma (including or excluding local or systemic therapy) in either eye
Uveitis or extraocular inflammation in either eye
Pseudoexfoliative syndrome
Known ocular ischemia syndrome in either eye (occlusion of extraocular arteries, influencing the vascularisation of the study eye)
Retinal venous occlusion in the study eye
History of retinal detachment (including or excluding any therapy) in either eye
Tractive retinal detachment due to diabetic epiretinal proliferation in the study eye
Intravitreal hemorrhage interfering with the assessment of the posterior pole in the study eye prior to baseline
Active malignancies (history of successful treated malignancies is not an exclusion criterion)
History of cerebral vascular accident or myocardial infarction within 12 months prior to baseline
Diabetes mellitus with HbA1c > 10 % or if it can be expected that the patient’s diabetes cannot be controlled adequately during the trial
Uncontrolled arterial Hypertension defined as a systolic value of > 180 mmHg and/or a diastolic value of > 110 mmHg
Systemic therapy with steroids or anticoagulative therapy with coumarin derivatives or heparin (Aspirin or Clopidogrel is allowed)
History of allergy to fluorescein or ranibizumab
Women who are pregnant or planning a pregnancy
Women who are breast feeding
Inability to comply with study or follow-up procedures
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E.5 End points |
E.5.1 | Primary end point(s) |
• Number of injections of study drug during the first year of treatment • Mean change from baseline in BCVA at month 12 (visit 13)
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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) |
• Proportion of patients with a vision acuity loss of fewer than 15 letters at month 12 (visit 13) compared with baseline • Proportion of patients with a vision acuity loss of more than 15 letters at month 12 (visit 13) compared with baseline • Proportion of patients with a treatment-free interval of at least 3 months duration at any time point following visit 3 • Drop out rates • Rate of non-responders • Retinal lesions • Changes in retinal thickness from baseline at month 4 and 12 (visit 13) • AEs
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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 | 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 | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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The trial duration will be 12 months |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |