E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
NonProliferative Diabetic Retinopathy |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.1 |
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 | 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 |
The primary objective of the study is to assess the efficacy of intravitreal (IVT) aflibercept compared to sham treatment in the improvement of moderately severe to severe nonproliferative diabetic retinopathy (NPDR). |
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E.2.2 | Secondary objectives of the trial |
To characterize the safety of IVT aflibercept in patients with moderately severe to severe NPDR
To determine if IVT aflibercept will prevent the worsening of diabetic retinopathy and reduce the incidence of diabetic macular edema (DME)
To determine the anatomic effects of IVT aflibercept in patients with moderately severe to severe NPDR. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men or women ≥18 years of age with type 1 or 2 diabetes mellitus who have moderately severe to severe NPDR (DRSS levels 47 or 53), confirmed by the central reading center, in whom PRP can be safely deferred for at least 6 months per the investigator
2. BCVA ETDRS letter score in the study eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better)
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E.4 | Principal exclusion criteria |
1.Presence of DME threatening the center of the macula in the study eye
2.Evidence of retinal neovascularization on clinical examination or Fluorescein Angiography (FA)
3.Any prior focal or grid laser photocoagulation or any prior PRP in the study eye
4.Any prior systemic anti-VEGF treatment or IVT anti-VEGF treatment in the study eye
5.Any prior intraocular steroid injection in the study eye
6.Current anterior segment neovascularization (ASNV), vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients who have improved by ≥2 steps from baseline on the Diabetic Retinopathy Severity Scale (DRSS) score at week 24
Proportion of patients who have improved by ≥2 steps from baseline on the DRSS score at week 52 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Proportion of patients developing a vision-threatening complication due to diabetic retinopathy
Proportion of patients who develop CI-DME
Time to development of a vision-threatening complication
Time to development of CI-DME
Proportion of patients who receive PRP, inclusive of patients undergoing vitrectomy with endolaser
Area under the curve (AUC) for change in BCVA from baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 52
Week 100 (exploratory manner) |
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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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Sham-controlled. (Fake) sham injection a syringe will be used but no needle will be attached. |
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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-controlled. (Fake) sham injection a syringe will be used but no needle will be attached. |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 | No |
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 |
Germany |
Hungary |
Japan |
United Kingdom |
United States |
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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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Last Visit Last Subject (LVLS) |
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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 | 4 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 21 |