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” or neovascular (“new blood vessel growth”) Age-Related Macular Degeneration (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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064930 |
E.1.2 | Term | Age-related macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025409 |
E.1.2 | Term | Macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067791 |
E.1.2 | Term | Wet 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 |
Assess the effect of treatment with regorafenib eye drops on visual acuity at Study Week 4 and at Study Week 12 in subjects with subfoveal choroidal neovascularization due to age related macular degeneration.
For Part B: in addition, explore an optimal dosing regimen |
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E.2.2 | Secondary objectives of the trial |
Evaluate the effect of treatment with regorafenib eye drops on ocular safety and tolerability |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Eligible subjects will have received a diagnosis of neovascular age-related macular degeneration in one or both eyes; however, only one eye will be enrolled in this study, the study eye. All ophthalmic eligibility criteria apply only to the study eye unless otherwise specified. The main criteria for inclusion in Part A and Part B are:
• Signed informed consent
• Men and women ≥ 50 years of age
• Active primary subfoveal choroidal neovascularization lesions secondary to age related macular degeneration, including juxtafoveal lesions that affect the fovea as evidenced by fluorescein angiography in the study eye and reviewed by the central reading center
• Evidence of intraretinal and/or subretinal fluid on OCT and reviewed by the central reading center
• The area of choroidal neovascularization must occupy at least 50% of total lesion in the study eye, as determined by fluorescein angiography review at the central reading center
• Evidence of intraretinal and/or subretinal fluid on optical coherence tomography
• Early Treatment Diabetic Retinopathy Study best corrected visual acuity of 73 to 25 letters (20/40 to 20/320 Snellen equivalent) in the study eye
• Willing, committed, and able to return for all clinic visits and complete all study related procedures
Subjects who participate in Part A of the protocol are ineligible for Part B.
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E.4 | Principal exclusion criteria |
1.Concurrent disease in the study eye, other than AMD (e.g., corneal diseases and dystrophies, conjunctival diseases, eye lid abnormalities, or any other diseases of the cornea and macula, or optic nerve abnormality) that could compromise visual acuity, likely require medical or surgical intervention during the study period, would limit the potential to gain or lose vision during study treatment, or could otherwise confound interpretation of the results
2.Any findings in the study eye that would limit the potential to benefit from study treatment, or could otherwise confound interpretation of the results such as total lesion size (including structural damage to the center of macula, neovascularization, scar, blood) >12 disc areas (30.5 mm2) and subfoveal fibrosis as assessed by FA
3.Only one functional eye, even if that eye is otherwise eligible for the study
4.Prior ocular or systemic treatment or surgery for neovascular AMD in the study eye except dietary supplements or vitamins
5.Prior treatment with any systemic anti-VEGF agent
6.Use of systemic or ocular treatment with an investigational drug within 12 weeks prior to start of study treatment
7.Any other condition that would require frequent chronic co-administration of other topical eye medications that would interfere with study drug administration
8.Symptoms or conditions consistent with contraindications listed in the current local label for ranibizumab
9.Participation in an investigational study within 30 days prior to start of study treatment that involved treatment with any drug (excluding vitamins and minerals) or device
10.Lactating women and women of child-bearing potential with either a positive pregnancy test result or no pregnancy test at s are excluded. Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential.
12.History or current use of long-acting steroids, either systemically or injected intraocularly, periocularly, subconjunctivally
15. Intraocular pressure ≥ 25 millimeters of mercury (mmHg) in the study eye as well as uncontrolled glaucoma
For more information please refer to protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variables in both Part A and Part B are the mean change
from baseline in best corrected visual acuity as measured by Early Treatment
Diabetic Retinopathy Study letter score at Study Week 4 and Study Week 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study Week 4 and Study Week 12 |
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E.5.2 | Secondary end point(s) |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Therapy, Safety and Efficacy for both parts; additionally, dose response for part B only |
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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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Part A: single-arm, open-label design Part B: double-masked, active-controlled |
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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 |
Comparator: other medicinal product and placebo only for part B |
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E.8.2.4 | Number of treatment arms in the trial | 8 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
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 |
Austria |
Brazil |
Canada |
Chile |
Colombia |
Czech Republic |
France |
Germany |
Hong Kong |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lithuania |
Mexico |
Netherlands |
Peru |
Poland |
Portugal |
Singapore |
Slovakia |
Spain |
Switzerland |
United Kingdom |
United States |
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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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For each participating EU country, the end of the study according to the EU Clinical Trial Directive will be reached when the last visit of the last subject for all centers in the respective country has occurred. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |