E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with type I or type II diabetes mellitus and high risk diabetic retinopathy. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with type I or type II diabetes mellitus and high risk diabetic retinopathy. |
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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 | 10036857 |
E.1.2 | Term | Proliferative diabetic retinopathy |
E.1.2 | System Organ Class | 100000004853 |
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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 compare the efficacy of ranibizumab 0.5 mg intravitreal injections plus panretinal photocoagulation versus panretinal photocoagulation alone on the regression of the neovascularization area in patients with high-risk proliferative diabetic retinopathy over a 12-month treatment period. |
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E.2.2 | Secondary objectives of the trial |
To compare the following parameters between the two treatment arms: - Changes in Best Corrected Visual Acuity from baseline to Month-12. - Time to complete neovascularization regression. - Recurrence of neovascularization. - Changes in the macular retinal thickness assessed by Optical Coherent Tomography from the baseline to Month-12. - Need of treatment for diabetic macular edema. - Need of vitrectomy due to the occurrence of vitreous haemorrhage, tractional retinal detachment or other complications of diabetic retinopathy. - Treatment safety profile. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.High-risk proliferative diabetic retinopathy (HR-PDR); i. Neovascularization in the disc ≥ 1/4 disc area OR Neovascularization Elsewhere ≥ 1/2 disc area; ii. Neovascularization Elsewhere < 1/2 disc area + vitreous and/or pre-retinal haemorrhage and/or rubeosis; iii. Neovascularization in the disc <1/4 disc area + vitreous and/or pre-retinal haemorrhage and/or rubeosis; 2. Best-corrected visual acuity at baseline ≥ 24 ETDRS letters score (approximate Snellen equivalent 20/320). 3. Type I or Type II diabetic subjects of either gender; 4. Age ≥ 18 years; 5. Ability to provide written informed consent; 6. Ability to return for all clinical trial visits.
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E.4 | Principal exclusion criteria |
1. Any intraocular surgery within 6 months before trial enrolment, including: a. Prior scatter (panretinal) or focal/grid photocoagulation; b. Eyes who have received YAG laser, or peripheral retinal cryoablation, or laser retinopexy (for retinal tears only); 2. Fibrovascular proliferation with retinal traction; 3. Other cause of retinal Neovascularization (retinal vein occlusion, radiation retinopathy or others); 4. Atrophy/scarring/fibrosis/ hard exudates involving the centre of the macula; 5. Significant media opacities or inadequate pupillary dilation, which might interfere with visual acuity, assessment of toxicity or fundus photography; 6. Any likelihood that the subject will require cataract surgery within the following 1 year; 7. Diabetic macular edema with central involvement, i.e., central macular thickness (Central Point Thickness) > 300 µm (Stratus OCT) equivalent values measured by SD-OCT, adjusted according to the SD-OCT machine used; 8. Previous vitrectomy; 9. Intraocular pressure > 21 mmHg; 10. Previous anti-VEGF therapy within the last 3 months; 11. Previous treatment with periocular and/or intravitreal corticosteroids within the last 3 months; 12. Known serious allergies or history of hypersensitivity to fluorescein used in angiography, or to components of Lucentis® formulation; 13. Acute ocular or periocular infection; 14. Active severe ocular or periocular inflammation; 15. Previous filtering surgery (e.g., trabeculectomy) or placement of a glaucoma drainage device (e.g., tube-shunt surgery). 16. Systolic BP > 170 mmHg or diastolic BP > 100 mmHg; 17. HbA1C level >11% or recent signs of uncontrolled diabetes; 18. Any of the following underlying systemic diseases: a. History or evidence of severe cardiac disease, e.g. NYHA Functional Class III or IV, clinical or medical history of unstable angina, acute coronary syndrome, myocardial infarction, or revascularization procedure within 6 months prior to baseline, or ventricular tachyarrhythmia requiring treatment; b. History or evidence of clinically significant peripheral vascular disease such as intermittent claudication or prior amputation; c. Renal failure requiring dialysis or renal transplant or renal insufficiency with creatinine levels > 2.0 mg/dl at screening; d. Stroke (within 12 months of trial entry); e. Any major surgical procedure within one month before trial enrolment; 19. Subject with a condition (such as advanced, severe or unstable disease or its treatment) or is in a situation which may put him/her at significant risk, which may confound the study results or may interfere significantly with the subject’s participation in the study; 20. Previous radiation to the head in the region of the study eye; 21. Use of any other investigational drugs within the last 3 months (for Diabetic Retinopathy or other condition); 22. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases; 23. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation. 24. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant UNLESS they are: using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices - IUDs). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) are not acceptable. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Regression of neovascularization, defined as any decrease in the area of neovascularization, from the baseline to Month-12 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening Visit, Month 3, Month 7 and Month 12 |
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E.5.2 | Secondary end point(s) |
- Best-corrected visual acuity - changes from baseline to Month 12 - Time to complete neovascularization regression - Recurrence of neovascularization - Macular retinal thickness - changes from baseline to Month 12, assessed by OCT - Need of treatment for Diabetic Macular Edema - Need of vitrectomy due to the occurrence of vitreous hemorrhage, tractional retinal detachment or other complications of diabetic retinopathy - Adverse events related to the treatments. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening Visit, Month 3, Month 7 and Month 12 |
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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) | 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 | Yes |
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 |
Panretinal Photocoagulation |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 end of the trial is the date of 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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |