E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to advanced Fuchs endothalial corneal dystrophy (FECD) |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to advanced disease of the cornea (Fuchs' cornea dystrophy) |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062973 |
E.1.2 | Term | Fuchs' endothelial dystrophy |
E.1.2 | System Organ Class | 100000004850 |
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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 determine the safety and tolerability of ripasudil 0.4% eye drops administered 3 times daily for up to 3 months after descemetorhexis in patients with moderate to advanced FECD compared to placebo |
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E.2.2 | Secondary objectives of the trial |
• To assess the rate of AE, AR, SAE, SAR and SUSAR within the observation period of 6 months after descemetorhexis • To assess the effect of ripasudil on corneal endothelial cell density (ECD) within the period of 6 months after descemetorhexis • To assess the effect of ripasudil on corneal thickness within the period of 6 months after descemetorhexis • To assess the effect of ripasudil on visual acuity (BCVA) within the period of 6 months after descemetorhexis • To assess the effect of ripasudil on contrast sensitivity within the period of 6 months after descemetorhexis • To assess the need of rescue therapy (DMEK) during the observation period
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent obtained from the subject 2. Understanding of study procedures and willingness to abide by all procedures during the course of the study. 3. Age range: 18-95 years 4. Diagnosis of moderate to advanced FECD with central guttae and clinical relevant corneal endothelial cell loss of <1,000 cells/mm2 and clinical indication of surgical intervention (descemetorhexis) with or without accompanying cataract operation 5. Reduced visual acuity, defined as BCVA <20/30 6. Woman of childbearing potential must be using a highly effective method of birth control. |
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E.4 | Principal exclusion criteria |
1. Clinical signs or suspicion of an acute infection 2. Acute ophthalmic infection (bacterial, viral or fungal) 3. Any known ophthalmic disease other than FECD and/or cataract 4. Known contra-indications for ripasudil or comparator 5. Use of soft lenses 6. Known severe comorbidities which may interfere with an ophthalmic surgical procedure at the discretion of the investigator 7. Use of any inadmissible medication, e.g. glucocorticoids (any systemic administration; if topically administered any glucocorticoid eye drops to be administered >2 times per day) 8. Nursing mother or pregnant woman, as verified by a positive pregnancy test. 9. Known hypersensitivity to the IMPs (ripasudil or comparator), or any of their formulation ingredients. 10. Treatment of dry eyes, such as artificial tears or hygienic eye lid cleaning 11. Known hypersensitivity to concomitant ophthalmic medication (e.g. antibiotic eye drops or glucocorticoid-containing eye drops) 12. Subject who is imprisoned or is lawfully kept in an institution. 13. Employee or direct relative of an employee of the study site or the sponsor 14. Participation in an interventional clinical study with an IMP within the last 4 weeks 15. Previous participation in this clinical trial
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary safety endpoint is defined as the incidence of AR and SAR within the observation period of 3 months after descemetorhexis |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 months after start of intervention |
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E.5.2 | Secondary end point(s) |
- Resolution of corneal edema within the observation period of 6 months after descemetorhexis - Reestablishment of a continuous endothelial cell layer within the observation period of 6 months after descemetorhexis - Improvement of BCVA, defined as improvement of at least of two lines of BCVA related to the individual preoperative value within the observation period of 6 months after descemetorhexis - Improvement of contrast sensitivity, defined as improvement of at least two lines in Mars Charts) related to the individual preoperative value within the observation period of 6 months after descemetorhexis
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 months after start of intervention |
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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 | 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 | Yes |
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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |