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 |
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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 |
Primary: To demonstrate that brolucizumab 6 mg with one (initial) injection followed by q12w maintenance is noninferior to brolucizumab 6 mg with 3x q4w loading injections followed by q12w maintenance |
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E.2.2 | Secondary objectives of the trial |
- To evaluate treatment interval prolongation compared to previous treatment - To estimate the proportions of patients maintained at q12w Treatment frequency in the two brolucizumab groups - To evaluate the functional outcomes comparing the two brolucizumab groups - To evaluate the anatomical outcomes comparing the two brolucizumab groups - To assess the safety and tolerability of brolucizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed informed consent - Male or female patients, ≥ 50 years of age at screening.
Study eye: 3. Active choroidal neovascularization (CNV) secondary to AMD 4. Previous treatment with any licensed anti-VEGF drug for ≥ 6 months in a ≥ q6w to ≤ q10w injection interval with residual or recurrent fluid 5. BCVA score must be ≤ 83 and ≥ 38 letters at 4 meters starting distance using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts |
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E.4 | Principal exclusion criteria |
1. Concomitant conditions or ocular disorders in the study eye 2. Treatment with anti-VEGF drugs for > 36 months. 3. Any active intraocular or periocular infection or active intraocular inflammation 4. Uncontrolled glaucoma in the study eye 5. Presence of amblyopia, amaurosis or ocular disorders in the fellow eye 6. Atrophy or fibrosis involving the center of the fovea in the study eye 7. The total area of fibrosis or subretinal blood affecting the foveal center point comprising ≥ 50% of the lesion area as well as chronic cystic lesions in the study eye 8. Structural damage within 0.5 disc diameter of the center of the macula in the study eye
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change in BCVA from baseline to mean of visits at week 40 to week 52 (non-inferiority margin -4 ETDRS letters) |
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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) |
- Mean treatment interval (overall as well as per study group comparing treatment intervals from baseline to week 52 in the study vs. 24 weeks to baseline prior to enrollment) - Rate of patients (overall and per group) with prolonged interval compared to mean treatment interval in last 24 weeks prior to enrollment - Comparison of proportions of patients maintained at a q12w interval at week 52 between the two arms - Distributions of patients at q8w/q12w intervals from baseline to week 52 - Average change in BCVA from baseline to week 52 - Proportions of patients with BCVA improvements of ≥5, ≥ 10, and ≥ 15 letters from baseline to week 52 - Proportions of BCVA ≥ 69 letters at week 52 - Mean change in BCVA from baseline to mean of visits week 16 to week 28 - Change from baseline in CST - Absence of IRF, SRF, and sub-RPE fluid - Presence of active CNV leakage - Incidence of ocular and non-ocular AEs up to week 52 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
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 |
Brolucizumab 6 mg „loading“ vs. Brolucizumab 6 mg „non-loading“ |
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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 | 54 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
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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 | 5 |
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 | 5 |