E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
persistent diabetic macular edema or persistent active neovascularisation following lasercoagulation |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012689 |
E.1.2 | Term | Diabetic retinopathy |
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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 |
Primary objectives: - For Group A (persitient macular edema): To investigate the change in macular edema measured with standard optical coherence tomography (OCT) and the absolute change in visual acuity following intravitreal administered injections of Bevacizumab (Avastin®) compared with non-treatment control in patients with persistent diabetic macular edema following grid lasercoagulation. - For Group B (persistent neovascularisation):∑ For Group B (persistent neovascularisation): To investigate the change of neovascularisation and vitreous hemorrhage following intravitreal administered injections of Bevacizumab (Avastin®) compared with non-treatment control as assessed by fundus photography and fluorescence angiography and the absolute change in visual acuity. |
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E.2.2 | Secondary objectives of the trial |
- To explore the structural mechanisms of Bevacizumab (Avastin®) on persistent diabetic macular edema or persistent neovascularisation as assessed by fundus photography, fluorescein angiography, and ultra high-resolution optical coherence tomography. - To investigate the safety and tolerability of Bevacizumab (Avastin®), a recombinant humanized anti-VEGF monoclonal antibody, administered as multiple intravitreal injections in patients with persistent diabetic macular edema or persistent neovascularisation following lasercoagulation.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria Group A: - Signed informed consent - Age ≥18 years - Patients with type 1 or type 2 diabetes mellitus - Patients with persistent diabetic macular edema with center involvement following completed grid lasercoagulation in the study eye - Last perifoveolar laser treatment 3 months before study entry - Central macular thickness (macular edema) of at least 300 microns in the central subfield as measured by OCT - Not eligible for any currently approved treatments or experimental protocols - Best corrected visual acuity, using ETDRS charts, of 20/25 to 20/400 (Snellen equivalent) in the study eye - Patients with decrease in vision in the study eye due to foveal thickening from diabetic macular edema and not to other causes, in the opinion of the investigator - Patients without a necessity for panretinal laser photocoagulation for at least 3 months after study inclusion - If both eyes are eligible, the one with worse visual acuity will be selected for study treatment unless Inclusion Criteria Group B: - Signed informed consent - Age ≥18 years - Patients with type 1 or type 2 diabetes mellitus - Patients with persistent active neovascularisations following completed panretinal lasercoagulation (at least 2000 spots) in the study eye - Last laser treatment 2 months before study entry - Not eligible for any currently approved treatments or experimental protocols - Best corrected visual acuity, using ETDRS charts, of 20/20 to 20/400 (Snellen equivalent) in the study eye - If both eyes are eligible, the one with worse visual acuity will be selected for study treatment unless
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E.4 | Principal exclusion criteria |
- A condition that would preclude a patient for participation in the study in opinion of investigator, e.g., unstable medical status including glycemic control and blood pressure - History of systemic corticosteroids within 3 months prior to randomization or topical, rectal or inhaled corticosteroids in current use more than 3 times per week
Prior/Concomitant Treatment - Panretinal laser photocoagulation or macular laser photocoagulation within the past 2 months in the study eye - Previous treatment with intravitreal or sub-Tenon triamcinolone within the past 3 months in the study eye - Previous participation in clinical trial involving anti-angiogenic drugs (pegabtanib sodium, ranibizumab, anecortave acetate, protein kinase C inhibitor, etc.) - History of submacular surgery or other surgical intervention for diabetic macular edema except grid lasercoagulation in the study eye - Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals) Diabetic Retinopathy Characteristics - High risk proliferative diabetic retinopathy in the study eye without complete panretinal lasercoagulation and having a risk for intravitreal bleeding
Concurrent Ocular Conditions - Active intraocular inflammation (grade trace or above) in either eye - Vitreomacular traction in the study eye evident by OCT - Current vitreous hemorrhage in the study eye (Group A) - Infectious conjunctivitis, keratitis, scleritis, endophthalmitis as well as idiopathic or autoimmuneassociated uveitis in either eye - Structural damage to the center of macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of retinal pigment epithelium, subretinal fibrosis, laser scar within foveal avascular zone (FAZ) or organized hard exudate plaques (Group A) - Ocular disorders in the study eye including retinal vascular occlusion, retinal detachment, macular hole, choroidal neovascularisation - Intraocular surgery (including cataract surgery, YAG laser capsulotomy) in the study eye within 3 months preceding Day 0 - Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥25 mmHg despite treatment with anti-glaucoma medication) - History of glaucoma filtration surgery, corneal transplantation in the study eye Concurrent Systemic Conditions - Systemic hypertension (> 150/100 mmHg) - History of myocardial infarction (in anamnesis or signs in ECG) - History of congestive heart failure - History of stroke or transient ischemic attacks - Significant abnormalities on laboratory testing (signs of failure of kidney, liver disease) - Premenopausal women not using adequate contraception and pregnant or nursing women The following are considered effective means of contraception: surgical sterilization; use of oral contraceptives; barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel; an IUD; or contraceptive hormone implant or patch. - History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications - Current treatment for active systemic infection
Other - History of allergy to fluorescein, not amenable to treatment - Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded - Inability to comply with study or follow-up procedures
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E.5 End points |
E.5.1 | Primary end point(s) | |
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 | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Sham Injection without medication. Patients receiving the sham injections do not receive an actual i |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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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End of trial is at the Visit of Month 12.
Patients must be withdrawn under the following circumstances: ∑ at their own request ∑ if the investigator thinks that continuation would not be in the best interest of the patient ∑ if the patient violates the conditions laid out in the consent form/information sheet or disregards instructions by the study personnel and in case of: ∑ Severe intraocular inflammatory response ∑ Endophthalmitis ∑ Retinal detachment ∑ Lens damage
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |