E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ischaemic Diabetic Macular Oedema |
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E.1.1.1 | Medical condition in easily understood language |
Swelling of the central part of the retina( the macula)which is receiving a poor blood supply. |
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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 | 10057934 |
E.1.2 | Term | Diabetic macular edema |
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 | 10012689 |
E.1.2 | Term | Diabetic retinopathy |
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 | 10012688 |
E.1.2 | Term | Diabetic retinal oedema |
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 | 10012661 |
E.1.2 | Term | Diabetic eye disease |
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 | 10054372 |
E.1.2 | Term | Diabetic retinal edema |
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 | 10038925 |
E.1.2 | Term | Retinopathy diabetic |
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 | 10057915 |
E.1.2 | Term | Diabetic macular oedema |
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 | HLT |
E.1.2 | Classification code | 10012657 |
E.1.2 | Term | Diabetic complications ophthalmic |
E.1.2 | System Organ Class | 10014698 - Endocrine 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 | 10054109 |
E.1.2 | Term | Non-proliferative diabetic retinopathy |
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 | HLGT |
E.1.2 | Classification code | 10012653 |
E.1.2 | Term | Diabetic complications |
E.1.2 | System Organ Class | 10014698 - Endocrine 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 |
Is it possible to improve visual function, prove safety and acceptability of the use of Avastin eye injections in patients with diabetic ischaemic macular oedema? |
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E.2.2 | Secondary objectives of the trial |
1. Does Avastin therapy improve functional vision (based on self-reported quality of life measures)? 2. Are 6 weekly intravitreal injections acceptable (based on self-reported quality of life measures)? 3. Does Avastin therapy improve visual acuity (gain of 15 letters or more), contrast sensitivity, and reading speed, and improve relative change in macular thickness (as measured by OCT scan). 4. Is Avastin therapy in this group of patients safe? (Maintenance of foveal avascular zone, absence of toxicity on Electrophysiological tests / Humphrey 10-2 /autofluorescence/ GDx, maintenance of retinal sensitivity on microperimetry, maintenance of colour vision) 5. Is Avastin therapy in this group of patients cost-effective? (Measurement of EQ-5D scores).
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Assessment of central visual field changes in relation to macular disease remains difficult to correlate with current available technology. As part of the current project, we have the aim of developing new software for PROGRESSOR analysis which would analyse the Humphrey-10-2 (central) visual field data collected on patients with DIME, correlate with Microperimetry / Electrophysiology / clinical data, in order to establish usefulness of PROGRESSOR 10-2 for objective serial outcome measurements (of central macular function). We would then hope that this new software would be available to any eye department with a standard Humphrey perimeter. |
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E.3 | Principal inclusion criteria |
General Inclusion Criteria • Age >= 18 years and less than 75 years • Diagnosis of diabetes mellitus (type 1 or type 2) • Able and willing to provide informed consent Study Eye Inclusion Criteria The subject must have one eye meeting ALL of the inclusion criteria and NONE of the exclusion criteria listed below. • Best corrected ETDRS visual acuity LogMAR (and approximate Snellen equivalent), between 0.47-1.30, 10 working days of randomization. (Equivalent to 6/18 – 3/60) • On clinical exam, definite retinal thickening due to diabetic macular oedema involving the centre of the macula. • OCT central subfield >=250 µm within 10 working days of randomization. • In the opinion of the examining ophthalmologist laser treatment is ineffective or contraindicated because of the state of the Foveal avascular zone (reflecting at least moderate macular ischaemia) on fluorescein angiography. At the point when the ophthalmologist enters into the hospital medical notes that ths individual is not to have further laser treatment, the patient may be considered for inclusion into this study. • Patients with an enlarged foveal avascular zone (FAZ) of diameter ≥1000 µm or a non-intact perifoveal capillary ring at the margin of the FAZ with FAZ 700-1000 µm in the transit phase of FFA will be defined as having macular ischaemia.
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E.4 | Principal exclusion criteria |
General Exclusion Criteria • Unstable cardiovascular disease or significant renal disease, (defined as a history of chronic renal failure requiring dialysis or kidney transplant). • Known allergy to any component of any study drug. • Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). • Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischaemic attack, or treatment for acute congestive heart failure within 6 months prior to randomization. • Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization. • For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 12 months. • Any anti-VEGF treatment to either eye at any time.
Study Eye Exclusion Criteria • Insufficient patient cooperation to allow adequate fundus photographs. • Other causes of macular oedema • Presence of an ocular disease that in the opinion of the investigator, is responsible for visual loss (e.g. sub-foveal atrophy, optic atrophy, dense subfoveal hard exudates.) • Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal). • History of major ocular surgery (including vitrectomy, cataract extraction) within prior 4 months. • Insufficient Media clarity to allow adequate fundus photographs. • History of treatment for DME at any time in the past 4 months (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, anti-VEGF drugs, or any other treatment). • History of panretinal photocoagulation (PRP) within 4 months prior to randomization or anticipated need for PRP in the 6 months following randomization. • History of YAG capsulotomy performed within 2 months prior to randomization. • Aphakia. • Intraocular pressure >= 25 mmHg.
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E.5 End points |
E.5.1 | Primary end point(s) |
Stabilization of visual acuity (loss of less than 10 letters) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Each subject will be followed up for 12 months. This end point will be evaluated at 12 months |
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E.5.2 | Secondary end point(s) |
1. Functional vision changes based on self reported quality of life measures. 2. Acceptability of 6 weekly intravitreal therapy. 3. Improvement of visual acuity (gain of 15 letters or more), contrast sensitvity and reading speed. 4. Relative change in macular thickness as measured by OCT scan. 5. Maintenance of foveal avascular zone, absence of toxicity on electrophysiology tests, autofluorecence, GDx, maintenance of retinal sensitivity on micoperimetry, maintenance of colour vision. 6. Cost-effectiveness: measurement of EQ-5D scores.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Each subject will be followed up for 12 months. These secondary end points will be evaluated at 12 months |
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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 | 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 | No |
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 | 1 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 29 |