E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic Macular Edema (DME) |
|
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 |
|
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 stepwise that the mean average 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 non-inferior to 0.5 mg ranibizumab alone given PRN in patients with visual impairment due to DME and-if successful in the first step - to demonstrate superiority. 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. |
|
E.2.2 | Secondary objectives of the trial |
Main secondary objectives of the trial: •To investigate within the TE dosing concepts the impact of laser treatment on the number of retreatments up to Month 12 and Month 24. Interpretation of the corresponding results needs to be done under consideration of possible differences related to efficacy. •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 at Month 12 and at Month 24, 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 subfield thickness (CSFT) 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 from baseline to Month 12 and up to Month 24. |
|
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 are only permitted if, in the opinion of the investigator, they do not prevent improvement of visual acuity on study treatment.
|
|
E.4 | Principal exclusion criteria |
Ocular medical history 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. 2. History of retinal deachment, retinal tear or macular hole in the study eye.
Prior Ocular treatments 3. Any intraocular surgery in the study eye within 3 months prior to randomization. 4. History of vitrectomy in study eye regardless of time prior to randomization. 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 either eye (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, VEGF-Trap, etc.) within 3 months prior to randomization. 8. History of intravitreal corticosteroid treatment in phakic study eye. 9. Intravitreal corticosteroids in post-cataract surgery study eye (aphakic or pseudophakic, without damaged posterior capsule) within 3 months prior to randomization. 10. Ocular conditions in the study eye that require chronic concomitant therapy with topical ocular corticosteroids.
Systemic conditions or treatments 11. History of stroke within 6 months prior to enrollment. 12. Untreated diabetes mellitus 13. Conditions that require chronic concomitant therapy with systemically administered corticosteroids. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable 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. The primary analysis will be performed after all patients completed the Months 12 visit (or left the sudy before month 12) within the FAS (LOCF). access to the results will be restricted. Details will be specified in the Statistical Analysis Plan.
|
|
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 | 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 |
ranibizumab/laser photocoagulation |
|
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 | 10 |
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 |
|
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
|
When the last patient has completed the follow-up assessment of Visit 26 (Month 24), (last patient last visit) |
|
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 |