E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic Macular Edema (DME) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057934 |
E.1.2 | Term | Diabetic macular edema |
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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 that the mean change from baseline in Best Corrected Visual Acuity (BCVA) over a 12 month treatment period obtained with either a 0.5 mg ranibizumab “Treat and Extend” (TE) dosing regimen with adjunctive laser, and/or with 0.5 mg ranibizumab TE dosing regimen alone is at least non-inferior to 0.5 mg ranibizumab alone given PRN in patients with visual impairment due to DME to cover a potential superiority claim. The condition for the interpretation of these results is the assessment of the extent to which the TE dosing regimens could be maintained during the study duration. |
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E.2.2 | Secondary objectives of the trial |
Main secondary objectives of the trial:
•To demonstrate a stabilizing effect of adjunctive laser reflected in a lower number of study visits scheduled for treatment between Months 12 and 24, comparing 0.5mg ranibizumab TE dosing regimen with adjunctive laser with 0.5mg ranibizumab TE dosing regimen alone.
•To investigate the efficacy of 0.5 mg ranibizumab TE dosing regimen with adjunctive laser, 0.5 mg ranibizumab TE dosing regimen alone and 0.5 mg ranibizumab alone given PRN on vision-related functioning and well-being assessed during a period of 12 months, as measured by the overall score assessed by the National Eye Institute (NEI) Visual Function Questionnaire-25 (VFQ-25) and EuroQol EQ-5D.
•To compare the changes in development of central retinal thickness and central subfield thickness of 0.5 mg ranibizumab TE dosing regimen with adjunctive laser, 0.5 mg ranibizumab TE dosing regimen alone and 0.5 mg ranibizumab alone given PRN over time. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient 1. Male or female patients > 18 years of age who have signed an Informed Consent.
2. Patients with Type 1 or Type 2 diabetes mellitus (according to American Diabetes Association or World Health Organization [WHO] guidelines) with glycosylated hemoglobin (HbA1c) ≤ 12.0% at screening (Visit 1). Patients should be on diet, exercise, and/or pharmacological treatment for diabetes. Treatment for diabetes must have been stable for at least 3 month.
Ocular 3. Patients with visual impairment due to DME in at least one eye who are eligible for laser treatment in the opinion of the investigator. If both eyes are eligible, the one with the worse visual acuity, as assessed at Visit 1, will be selected by the investigator as the study eye.
4. BCVA ≥ 39 and . 78 letters in the study eye and, inclusively, using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/160) at screening.
5. Concomitant conditions in the study eye which, in the opinion of the investigator, do not prevent improvement of visual acuity on study treatment.
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E.4 | Principal exclusion criteria |
1. Structural damage within 0.5 disc diameter of the center of the macular in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques.
Prior Ocular treatments 2. Any intraocular surgery in the study eye within 3 months prior to randomization.
3. History of vitrectomy in study eye regardless of time prior to randomization.
4. Planned medical or surgical intervention during the 24-months study period.
5. Panretinal laser photocoagulation in the study eye within 6 months prior to randomization.
6. Focal/grid laser photocoagulation in the study eye within 3 months prior to randomization.
7. Treatment with anti-angiogenic drugs in the study eye (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, VEGF-Trap, etc.) within 3 months prior to randomization.
8. Use of other investigational drugs at the time of enrollment, or within 3 month or 5 half-lives from enrollment, whichever is longer.
9. History of intravitreal corticosteroid treatment in phakic study eye.
10. Intravitreal corticosteroids in post-cataract surgery study eye (aphakic or pseudophakic, without damaged posterior capsule) within 3 months prior to randomization.
11. Ocular conditions in the study eye that require chronic concomitant therapy with topical ocular or systemically administered corticosteroids.
Systemic conditions or treatments 12. History of stroke within 6 months prior to enrollment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the difference between the average level of BCVA (letters) over all monthly post-baseline assessments from Month 1 to Month 12 and the baseline level of BCVA. The last assessment collected prior to start of treatment will be considered the baseline value.
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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 | Yes |
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 |
ranibizumab/laser photocoagulation |
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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 | 76 |
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 | Information not present in EudraCT |
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 |
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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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When the last patient has completed the follow-up assessment of Visit 26 (Month 24), (last patient last visit) |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |