E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10057934 |
E.1.2 | Term | Diabetic macular edema |
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 demonstrate that brolucizumab is non-inferior to aflibercept with respect to the change in visual acuity from baseline up to week 52 |
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E.2.2 | Secondary objectives of the trial |
1. To assess the effect of brolucizumab compared with aflibercept with respect to anatomical outcomes
2. To assess the effect of brolucizumab compared with aflibercept with respect to visual acuity
3. To assess the effect of brolucizumab relative to aflibercept on the status of Diabetic Retinopathy
4. To assess the safety and tolerability of brolucizumab compared to aflibercept
5. To assess the immunogenicity of brolucizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1- Signed informed consent must be obtained prior to participation in the study
2- Patients to be 18 years of age or over at baseline
3- Patients with type 1 or type 2 diabetes mellitus and HbA1c ≤ 12% at screening
3- Patients with visual impairment due to DME with
-BCVA score between 73 and 23 letters, inclusive, using ETDRS visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/40 to 20/320) at both screening and baseline.
-DME involving the center of the macula, with CSFT ≥ 320 μm on SD-OCT at screening |
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E.4 | Principal exclusion criteria |
Ocular conditions
-High-risk proliferative diabetic retinopathy (PDR) in the study eye as per investigator assessment at both screening and baseline
-Concomitant conditions or ocular disorders in the study eye at screening or baseline which may, in the opinion of the investigator, confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the 12-month study period (eg, structural
damage of the fovea, vitreous hemorrhage, retinal detachment, vitreomacular traction, macular hole, retinal vein/arterial occlusion,
neovascularization of iris or choroidal neovascularization (CNV) of any cause).
-Any active intraocular or periocular infection or active intraocular inflammation in the either eye at screening or baseline.
-Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator’s judgment at
screening or baseline
-Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA <20/200 at screening (except when due to conditions whose surgery
may improve VA, eg, cataract)
Ocular treatments
-Use of anti-VEGF therapies, intraocular surgery or laser photocoagulation (macular or panretinal) in the study eye during the 3-month period prior to
baseline
-Use of intraocular or periocular corticosteroids including dexamethasone intravitreal implant (Ozurdex) in the study eye during the 6-month period
prior to baseline, and use of fluocinolone acetonide intravitreal (IVT) implant (Iluvien) at any time prior to baseline
-Prior investigational drugs in either eye, vitreoretinal surgery in the study eye at any time prior to baseline |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in BCVA 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) |
1.
-Change from baseline in CSFT at each post-baseline visit
-Proportion of study eyes with fluid-free macula at each post-baseline visit
-Proportion of study eyes with absence of DME (CSFT < 280 μm) at each post-baseline visit
-Time to first fluid-free macula
-Time to first absence of DME (CSFT < 280 μm)
2.
-Change from baseline in BCVA at each post-baseline visit
-Proportion of study eyes with gain in BCVA of 5/10/15 letters or more at each post-baseline visit compared to baseline
3.
-Change from baseline in ETDRS Diabetic Retinopathy Severity Scale (DRSS) score at Week 12, Week 24 and Week 52
4.
-Incidence of ocular and non-ocular Adverse Events (AEs)
5.
-Anti-drug antibody (ADA) measurement
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, Weeks 12, 24, 52 |
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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 | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 5 |
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 | 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 |
Hungary |
Israel |
Slovakia |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |