Limbal Stem Cells Deficiency Clinical Trial
— HOLOCOREOfficial title:
Multinational, Multicentre, Prospective, Open-label, Uncontrolled Clinical Trial to Assess the Efficacy and Safety of Autologous Cultivated Limbal Stem Cells Transplantation (ACLSCT) for Restoration of Corneal Epithelium in Patients With Limbal Stem Cell Deficiency Due to Ocular Burns (HOLOCORE)
| Verified date | March 2022 |
| Source | Holostem Terapie Avanzate s.r.l. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this trial is to confirm the efficacy of Holoclar at one year after the first treatment in patients suffering from moderate to severe LSCD (Limbal Stem Cell Deficiency) secondary to ocular burns. In case of failure of the treatment and upon clinical indication of the Principal Investigator, a second transplant with Holoclar will be offered if eligibility will be confirmed. The efficacy of two treatments with Holoclar at one year after the last treatment will be also evaluated. All patients will be followed-up for 12 months after each implant to determine the treatment efficacy by an Independent Assessor.
| Status | Completed |
| Enrollment | 70 |
| Est. completion date | March 11, 2022 |
| Est. primary completion date | December 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years and older |
| Eligibility | Inclusion Criteria: 1. Written informed consent prior to any study-related procedures. 2. Adult male and female patients (=18 years old); Five Paediatric patients aged 2 to 17 years will be also enrolled for safety purposes only. 3. LSCD secondary to unilateral or bilateral physical or chemical ocular burns, with at least 1-2 mm2 of undamaged limbus to harvest stem cells for expansion in culture. LSCD will be considered for inclusion in presence of superficial neo-vascularization invading at least two corneal quadrants with central corneal involvement (including corneal neo-vascularisation, corneal opacity or corneal dyschromia) according to the independent assessors; 4. Stability of LSCD, defined by a duration of disease of at least 24 months at the time of the Screening Visit and presence of continuum epithelium as per fluorescein staining scored as none or trace. 5. Presence of severe impairment in visual acuity defined by a score of 1/10th or below 20/200 at the Snellen chart (legal blindness) after best correction (i.e. Best Corrected Visual Acuity); 6. Absence of other clinical contraindications to ACLSC transplantation based upon investigator's judgment; 7. A cooperative attitude to follow up the study procedures (Caregivers in case of minors). Exclusion Criteria: 1. LSCD of mild degree (i.e. below 2 quadrants of neo-vessel invasion without central corneal), due to a recent burn (less than 24 months before screening), or secondary to medical conditions other than burns (i.e. radiotherapy); 2. Severe ocular inflammation according to the Efron Grading Scale for Contact Lens Complications. Patient can be re-screened after appropriate treatment; 3. Presence of eyelids malposition; 4. Conjunctival scarring with fornix shortening; 5. Severe tear secretion deficiency, determined by Schirmer's test type I (<5 mm/ 5 min); 6. Corneal anaesthesia and conjunctival anaesthesia; 7. Active local or systemic infections at the time of screening. Patient can be re-screened after appropriate treatment; 8. Diagnosis of local or systemic neoplastic disease; 9. Congenital diseases (i.e., Aniridia); 10. Bilateral inflammatory diseases (i.e. Stevens-Johnson syndrome, phemphigoid); 11. A pre-existing blindness precluding a functional recovery; 12. Female subjects: pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS are willing to use one or more reliable methods of contraception (i.e. contraceptive methods other than oral contraceptives, IUD, tubal ligature). Reliable contraception should be maintained throughout the study. Any postmenopausal women (physiologic menopause defined as "12 consecutive months of amenorrhea") or women permanently sterilized (e.g. tubal occlusion, hysterectomy or bilateral salpingectomy) may be enrolled in the study. Parental control will be applied for the pediatric population when needed. 13. Allergy, sensitivity or intolerance to concomitant drugs or excipients (Hypersensitivity to any of the excipients listed in section 6.1 or to bovine serum and murine 3T3-J2 cells); 14. Contraindications to the local or systemic antibiotics and/ or corticosteroids foreseen by the protocol; 15. Contraindications to the surgical procedure; 16. Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell transplantation based upon investigator's judgment or other concomitant medical conditions affecting grafting procedure; 17. Patients (or parents in case of paediatric subject) unlikely to comply with the study protocol or unable to understand the nature and scope of the study or the possible benefits or unwanted effects of the study procedures and treatments. 18. Participation in another clinical trial where investigational drug was received less than 4 weeks prior to screening visit. |
| Country | Name | City | State |
|---|---|---|---|
| Italy | Hospital San Raffaele | Milan |
| Lead Sponsor | Collaborator |
|---|---|
| Holostem Terapie Avanzate s.r.l. |
Italy,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Success of transplantation | The percentage of patients with a success of first transplantation at approximately 12 months from the first Holoclar treatment. Transplantation success is defined on the basis of the degree of "superficial corneal neo-vascularization" (CNV) and "epithelial defects". | 12 months after transplantation | |
| Secondary | Success of one or two transplantation(s) | The percentage of patients with clinical success after one or two ACLSCTs assessed at 12 months after the last treatment with Holoclar.
Transplantation will be considered successful on the basis of the degree of "superficial corneal neo-vascularization" and "epithelial defects" according to the same definition as for the primary efficacy endpoint assessment. |
12 months after the last transplantation |