E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
neovascular age-related macular degeneration |
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E.1.1.1 | Medical condition in easily understood language |
neovascular Age-Related Macular Degeneration (nAMD), also commonly referred to as wet AMD |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071129 |
E.1.2 | Term | Neovascular age-related macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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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 superior to aflibercept with respect to the duration of treatment intervals at Week 32 •To demonstrate that brolucizumab is non-inferior to aflibercept with respect to average change in BCVA from baseline at Weeks 28 and 32 |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the durability of brolucizumab relative to aflibercept •To evaluate the functional outcomes with brolucizumab relative to aflibercept •To evaluate the anatomical outcomes with brolucizumab relative to aflibercept •To evaluate the effect of brolucizumab relative to aflibercept on Patient-Reported Outcomes (PRO) •To assess the safety and tolerability of brolucizumab relative to aflibercept
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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.Male or female patients, ≥ 50 years of age at screening. Study Eye: 3.Active CNV secondary to AMD that affects the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by fluorescein angiography (or other imaging modalities) and sequellae of CNV, e.g. pigment epithelial detachment (PED), subretinal or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema. 4.Presence of intraretinal fluid (IRF) or subretinal fluid (SRF) that affects the central subfield, as seen by SD-OCT. 5.BCVA score must be ≤ 83 and ≥ 38 letters at an initial testing distance of 4 meters using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts (approximately Snellen equivalent of 20/25 and 20/200), at both screening and baseline.
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E.4 | Principal exclusion criteria |
1.Ocular conditions/disorders at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require planned medical or surgical intervention during the first 12-month study period, structural damage of the fovea, atrophy or fibrosis at the center of the fovea (study eye) 2.Any active intraocular or periocular infection or active intraocular inflammation, at screening or baseline (study eye) 3.Uncontrolled glaucoma defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator’s judgment, at screening or baseline (study eye) 4.Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 20/200 at screening (except when due to conditions which can lead to improved VA after surgery eg cataract) 5.Ocular treatments: previous treatment with any anti-vascular endothelial growth factor (VEGF) drugs or investigational drugs, intraocular or periocular steroids, macular laser photocoagulation, photodynamic therapy, vitreoretinal surgery, intraocular surgery (study eye) 6.Stroke or myocardial infarction during the 6-month period prior to baseline 7.Systemic anti-VEGF therapy at any time.
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Distribution of the last interval with no disease activity up to Week 32 (if there was disease activity, the last interval will be shortened by 4 weeks, down to a minimum of 4 weeks).Subjects who will be assigned to a 4-week interval will be analyzed in the q4w category, but discontinued from further study treatment. 2.Average change in BCVA from baseline at Weeks 28 and 32
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. up to week 32 2. at week 28 and 32
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E.5.2 | Secondary end point(s) |
1. Distribution of the last interval with no disease activity up to Week 64 (if there was disease activity, the last interval will be shortened by 4 weeks down to a minimum of 4 weeks).Subjects who will be assigned to a 4-week interval will be analyzed in the q4w category, but discontinued from further study treatment. 2. Distribution of the maximal intervals with no disease activity up to Week 64 3. Proportion of patients with no disease activity at Weeks 14 and 16 4. Time from the last loading injection to the first visit with no disease activity 5. Average change in BCVA from baseline at Weeks 60 and 64 6. Occurrence of BCVA improvements of ≥ 10 and ≥ 15 letters from baseline at Week 32, Week 64, and at the last injection visit 7. Occurrence of BCVA ≥ 69 letters at Week 32, at Week 64, and at the last injection visit 8. Average change from baseline in CSFT as assessed by SD-OCT at Weeks 28 and 32 9. Average change from baseline in CSFT as assessed by SD-OCT at Weeks 60 and 64 10. Number of visits with presence of IRF and/or SRF, and sub-RPE fluid in the central subfield, as assessed by SD-OCT at Weeks 28 and 32 11. Number of visits with presence of IRF and/or SRF, and sub-RPE fluid in the central subfield as assessed by SD-OCT at Weeks 60 and 64 12. Change in Visual Function Questionnnaire-25 (VFQ-25) total and subscale scores from baseline at Weeks 32 and 64 13. Incidence of Ocular and Non-ocular AEs, vital signs and laboratory values up to Week 64
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. up to Week 64 2. up to Week 64 3. at Weeks 14 and 16 4. Time from the last loading injection to the first visit with no disease activity 5. at Weeks 60 and 64 6. at Week 32, Week 64, and at the last injection visit 7. at Week 32, at Week 64, and at the last injection visit 8. at Weeks 28 and 32 9. at Weeks 60 and 64 10. at Weeks 28 and 32 11. at Weeks 60 and 64 12. at Weeks 32 and 64 13. up to Week 64 |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 69 |
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 |
Argentina |
Australia |
Canada |
Israel |
Korea, Republic of |
Malaysia |
Taiwan |
United States |
Austria |
France |
Sweden |
Netherlands |
Spain |
Switzerland |
Czechia |
Germany |
Italy |
Belgium |
Portugal |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 4 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 28 |