E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neovascular (wet) age-related macular degeneration |
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E.1.1.1 | Medical condition in easily understood language |
An eye disorder caused by abnormal blood vessels that leak fluid into the central part of the retina at the back of the eye leading to blurring or a blind spot in the central (straight ahead) vision |
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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 assess whether 2 mg intravitreal (IVT) aflibercept administered at a customized treatment interval (determined after the first extended treatment interval) is non-inferior to 2 mg IVT aflibercept administered according to a standard treat and extend (T&E) regimen (initiated after the first extended treatment interval) in patients with no fluid following treatment initiation for neovascular (wet) age-related macular degeneration (nAMD) |
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E.2.2 | Secondary objectives of the trial |
1. To assess treatment burden of 2 mg IVT aflibercept administered at a customized treatment interval compared with 2 mg IVT aflibercept administered according to a standard T&E regimen (initiated after the first extended treatment interval) in patients with no fluid following treatment initiation for nAMD 2. To evaluate the safety of aflibercept with proactive treatment intervals |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent and able to read (or if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member), understand, and willing to sign the ICF. 2. Men and women ≥50 years of age. 3. At treatment initiation, active macular neovascular lesions secondary to nAMD (Patients with polypoidal choroidal vasculopathy or retinal angiomatous proliferation are eligible to participate in the study, and their condition should be captured in the electronic case report form [eCRF]). 4. Treatment initiation with 3 × monthly IVT aflibercept injections (Weeks -16, -12, and -8 to planned study baseline visit) resulting in absence of any fluid at week -8. 5. ETDRS BCVA of at least 25 letters (20/320 Snellen equivalent) in the study eye at screening visit. 6. Willing, committed, and able to return for all clinic visits and complete all study-related procedures. 7. Able to use the provided monitoring device and willing to perform 5 × weekly self-assessments in the Investigator’s opinion. 8. Women and men of reproductive potential must agree to use adequate contraception when sexually active. This applies for the time period between signing of the ICF and 3 months after the last administration of study drug. |
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E.4 | Principal exclusion criteria |
1. Any contraindication to IVT anti-VEGF treatment or treatment with Eylea® as detailed in the Summary of Product Characteristics (SmPC). 2. Any prior ocular (in the study eye) or systemic treatment (including investigational agents) or surgery for nAMD, except the 3 × monthly IVT aflibercept injections required for treatment initiation and dietary supplements or vitamins. 3. Any presence of intraretinal and subretinal fluid. 4. Any ocular or systemic condition expected to interfere with study outcomes and procedures, including but not limited to: • Scar, fibrosis or other lesions (e.g., retinal pigment epithelium [RPE] tears, macular hole stage 2 or above and others) involving the center of the macula in the study eye. • Clinically relevant opacities or conditions involving the optic media including cataract, corneal dystrophies or s.p. corneal transplant in the study eye. • Uncontrolled glaucoma (defined as IOP ≥25 mm Hg despite treatment with antiglaucoma medication) in the study eye or prior trabeculectomy or other filtration surgery in the study eye. • Intraocular surgery, periocular surgery, or cataract surgery within 90 days before Day 1 in the study eye, except the IVT aflibercept injections required for treatment initiation and any history of vitrectomy, retinal radiation therapy, retinal detachment or treatment or surgery for retinal detachment in the study eye. • Aphakia or pseudophakia with absence of posterior capsule (unless as a result of an yttrium aluminum garnet posterior capsulotomy) in the study eye. 5. Participation as a patient in any clinical study within 12 weeks before screening. 6. Close affiliation with the investigational site; e.g., a close relative of the Investigator, dependent person (e.g., employee or student of the investigational site). 7. Previously screen failed patients for this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in best-corrected visual acuity (BCVA) (early treatment diabetic retinopathy study [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) |
1. Number of IVT aflibercept injections per patient 2. Number of IVT aflibercept injections per patient 3. Number of patients achieving pre-defined treatment intervals (≥4, ≥8, ≥10, ≥12¸ ≥14, and 16 weeks) 4. Change in BCVA (ETDRS letters) 5. Number of subjects with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From baseline up to Week 52 2. From baseline up to Week 36 3. At Weeks 36 and 52 4. From baseline up to Week 52 5. From baseline up to Week 36 and Week 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) | 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 |
Standard treat and extend regimen-2 week-adjustment |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Canada |
France |
Spain |
Germany |
United Kingdom |
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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 | 11 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 11 |