E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Limbal Stem Cell Deficiency of the Eye |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of patients with total limbal stem cells deficiency with moderate and severe symptoms, caused by severe exogenous trauma or endogenous eye disease |
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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 | 10063581 |
E.1.2 | Term | Stem cell transplant |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 restore the ocular surface epithelium by preventing recurrent conjunctivalization and neovacularization up to 12 months post transplantation. |
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E.2.2 | Secondary objectives of the trial |
Presence of a stable coreal epithilium and absence of conjunctivalisation at each follow-up visit at month 24 and 36. Prevention of recurrent neovacularization at each follow-up visit at month 24 and 36. To reduce the amount of punctate epithelial keratophathy. To increase the transparency of the epithelium at each follow-up visit. To improve visual acuity from Baseline to each follow-up visit. To improve photophobia, watering, and pain symptoms from Baseline to each follow-up visit. Change in patients' quality of life from Baseline to each follow-up visit (assessed by VFQ25 questionnaire).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for all patients: 1. Age ≥2 years to 74 years 2. Males or females with bilateral or unilateral total LSCD due to one of the following causes: a) Chemical burns b) Thermal burns c) Contact lens wear d) Surgery of the ocular surface e) Stevens-Johnson syndrome and other inflammatory disease under stable condition f) Aniridia 3. Documented conjunctivalization of the corneal surface, measured by fluorescein staining 4. Stable disease, i.e. history of LSCD for at least 6 months 5. Clinical signs indicative of conjunctivalisation: a) Superficial blood vessels on the corneal surface b) Loss of epithelial transparency or persistent epithelial defect 6. Healthy oral mucosa 7. Absence from tobacco and alcohol (7 days before the biopsy) 8. Regular tooth brushing (at least twice daily) 9. Ability to comply with the protocol 10. Covered by a social security system 11. Signed informed consent form, ability to understand the study procedures, and contractual capability. Applicable to patient or legal carer (including parent)
Special inclusion criteria for patients between 18 and 74 years of age (adults): 12. Multiple surgeries in the limbal region |
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E.4 | Principal exclusion criteria |
Exclusion criteria for all patients: 1. Acute systemic infection 2. Acute ocular inflammation in the previous 6 months 3. Previous neoplastic/cancer disease 4. Severe dry eye confirmed by a Schirmer test 5. Lyell-Syndrome, epidermolysis bullosa 6. Total symblepharon 7. Medical history of hypersensitivity or allergy to bovine or murine derived materials 8. Pregnant and lactating patients, positive urine pregnancy test in women of childbearing potential 9. Any systemic infectious disease as diagnosed by serology tests such as syphilis, HIV-1, HIV-2, hepatitis B or C, or HTLV-1 infection at screening and at the day of the biopsy 10. Current or previous (within 30 days of enrolment) treatment with another investigational drug or participation in another clinical study 11. Previous participation of the patient in this study 12. Evidence of any other medical conditions (such as psychiatric illness, physical examination or laboratory findings) that may interfere with the planned treatment, affect patient compliance or place the patient at high risk of treatment-related complications 13. Employees of the sponsor or patients who are employees or relatives of the investigator 14. Genetic conditions such as ectodermal dysplasia or multiple endocrine neoplasia
Special exclusion criteria for patients ≥2 and <18 years of age (children): 15. Multiple surgeries in the limbal region |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Presence of a stable epithelium on cornea and absence of conjunctivalization in the visual axis at month 12 (success is defined as the absence of goblet cells, indicative of corneal phenotype) assessed by delayed fluorescein staining and impression cytology 2. Extent of neovascularization at month 12 (success is defined as a reduction of ≥50% compared to Baseline
Criteria for evaluation - children As for primary endpoint No.1, assessments are only performed if investigator considered them feasible. Other than this item, the primary endpoint No.2 for adult patients will be applied for children. |
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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. Presence of a stable corneal epithelium and absence of conjunctivalization in the visual axis at each follow-up visit at month 24 and 36 assessed by delayed fluorescein staining and impression cytology 2. Extent of neovascularization at each follow-up visit at month 24 and 36 (success is defined as a reduction of ≥50% as compared to Baseline) 3. Punctate epithelial keratopathy at each follow-up visit 4. Improvement of visual acuity from Baseline to each follow-up visit 5. Change in quality of life assessed by the National Eye Institute Visual Functioning Questionnaire 25 (VFQ25) from Baseline to each follow-up visit (a modified VFQ25 will be used for children and for unilateral cases) 6. Presence of a transparent epithelium in the visual axis at each follow-up visit 7. Improvement of photophobia from Baseline to each follow-up visit 8. Improvement of watering from Baseline to each follow-up visit 9. Improvement of pain from Baseline to each follow-up visit 10. Suitability and risk status for a corneal graft (lamellar or full thickness) at month 12
Criteria for evaluation - children As for secondary endpoint No. 1 and 4, assessments are only performed if investigator considered them feasible. Other than these items, the secondary endpoint No. 2, 3, 5 for adult patients will be applied for children. |
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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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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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The end of the study is defined as the day of the last patient’s data obtained. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |