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 |
Wet age-related macular degeneration (wet AMD) is an ophthalmic disorder. Wet AMD retinal degeneration leads to pathological growth of new blood vessels in the central part of the retina. |
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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 study the efficacy and safety of zoledronic acid as systemic adjuvant therapy for neovascular age-related macular degeneration (AMD).
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Active, treatment-naïve neovascular AMD in the study eye, intraretinal or subretinal fluid involving the fovea centre on optical coherence tomography (OCT), and evidence of choroidal neovascularization on fluorescein angiography (FA) and/or OCT angiography (OCT-A). 2. Age ≥50 years 3. Best-corrected visual acuity (BCVA) between 0.1 and 1.0 logMAR 4. Menopausal for at least one year 5. Only one eye per patient will be recruited for the study. If both eyes are eligible for the study, the eye with the worse best-corrected visual acuity (BCVA) will be selected as the study eye. 6. Subjects must give written informed consent before any study related procedures are performed
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E.4 | Principal exclusion criteria |
1. Lesions comprising more than 50% blood or fibrosis involving the fovea centre 2. Polypoidal choroidal vasculopathy (PCV) - indocyanine green is performed at the discretion of the investigator on clinical suspicion of PCV 3. Presence of other ocular disease causing concurrent vision loss 4.Presence of ocular disease making intravitreal treatment contraindicated (e.g. current ocular or periocular infection, active uveitis or uncontrolled glaucoma/intraocular pressure ≥ 25 mmHg) 5.Systemic anti-vascular endothelial growth factor (anti-VEGF) within one year preceding the initial study treatment 6. Bisphosphonate treatment for osteoporosis within ten years preceding the initial study treatment , or any prior bisphosphonate treatment as an adjuvant to cancer therapy 7.Confirmed or suspected active malignancy. 8.Other factors (i.e. lack of cooperation) that, in the opinion of the investigator, can interfere with the study protocol 9.Known or suspected hypersensitivity to any of the trial products 10.Hypocalcemia (total Ca < 2.15 mmol/L) 11. Renal impairment (estimated ClCR < 35 ml/min) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is mean change in best-corrected visual acuity (BCVA) |
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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) |
The number of anti-VEGF intravitreal injections given Number of patients with a change in BCVA of 0.3 logMAR or more Mean change from baseline in central retinal thickness (CRT) Proportion of patients with refractory nAMD EQ 5D (ranging from 0-1; 0 designates “dead” and 1 designates “perfect health) and NEI-VFQ-25 score (ranging from 0 to 100 where 100 reflects best vision-specific health) at 1 year compared to baseline. Proportion of patients experiencing adverse events of special interest (ESI): osteonecrosis of the jaw or atypical femoral fracture, endophthalmitis or orbital, scleral, or serious intraocular inflammation (grade 4 aqueous cells/FLARE).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
assessed after 52 weeks with the exception of disease remission, which will be assessed after 6 months |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | |
E.8.9.1 | In the Member State concerned days | |