E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Ocular Surface Disease (OSD) |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067103 |
E.1.2 | Term | Ocular surface disease |
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 |
- Determination of feasibility, efficacy and safety of transplantation of ex vivo expanded corneal limbal stem cells
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E.2.2 | Secondary objectives of the trial |
- Assessment of improvement in vision and quality of the ocular surface
- Assessment of comparision of immunosuppression and limbal stem cell transplantation with using immunosuppression and amniotic membrane alone
- To generate the data required for reliable sample size calculations for subsequent studies
- To evaluate all the practicalities and logistics of the study including the recruitment process, follow-up procedures, data collection and analysis
- To obtain information on actual recruitment rate |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult patients, of either sex, with bilateral corneal blindness due to limbal stem cell deficiency
- Visual acuity less than 3/60 in the better eye
- Severe, debilitating corneal disease with extremely low chance of successful outcome with limbal and corneal graft surgery
- Functioning retina indicated by light perception and ultra-sonographic examination to exclude retinal detachment
- Normal intra-ocular pressure
- Schirmer’s test at least 50% normal values |
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E.4 | Principal exclusion criteria |
- Inability to give informed, comprehending consent
- Unfitness for local or general anaesthesia
- Inability to self-administer medication
- Inability to tolerate immunosuppressive therapy
- Severe dry eyes
- Patients with corneal anaesthesia
- Patients with severe lid deformities
- Patients with uncontrolled glaucoma or drainage procedures |
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E.5 End points |
E.5.1 | Primary end point(s) |
The best visual acuity will be calculated for each patient from all post treatment observations available |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The main analysis will take place when patients have finished all follow-ups. An interim analysis will also take place after all patients have completed 9 months of follow-up. |
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E.5.2 | Secondary end point(s) |
- Ocular surface score – image analysis based evaluation of area of neovascularisation, area of opacity and degree of abnormal fluorescein staining
- Quality of Life – as assessed by validated questionnaires VF14 and SF36
- Successful re-establishment of corneal surface after treatment, defined as absence of corneal vascularisation, absence of goblet cells on the cornea surface, absence of persistent epithelial defects, smooth corneal epithelium and no staining with fluorescein, non-fibrotic and normal limbal anatomy
- Engraftment of donor cells |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The main analysis will take place when patients have finished all follow-ups. An interim analysis will also take place after all patients have completed 9 months of follow-up. |
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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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 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 | Information not present in EudraCT |
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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The end of trial is defined as last visit that the last patient will be seen during the follow up period.
Following the surgical procedure (implant of clinical product), patients will be seen 1, 3, 7 and 14 days after surgery.
Following this they will be seen at regular intervals at 1, 3, 6, 9, 12, 15 and 18 months. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |