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Efficacy and Safety of Autologous Cultivated Limbal Stem Cells Transplantation (ACLSCT) for Restoration of Corneal Epithelium in Patients With Limbal Stem Cell Deficiency (HOLOCORE)

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ClinicalTrials.gov Identifier: NCT02577861
Recruitment Status : Recruiting
First Posted : October 16, 2015
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Chiesi Farmaceutici S.p.A.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Limbal Stem Cells Deficiency Procedure: Biopsy from donor eye Procedure: Implant of Holoclar Procedure: Ophtalmologic examination Procedure: Blood sample collection Procedure: Digital pictures Procedure: ECG Behavioral: Questionnaires Procedure: Physical examination and vital signs Phase 4

Detailed Description:

This is a multinational, multicentre, prospective, open label, uncontrolled clinical trial.

Patients will be screened according to the Study Inclusion and Exclusion criteria and will be candidates for the ACLSCT if all eligibility criteria are met.

Patients then will undergo limbal biopsy for the collection of limbal stem cells for product manufacturing. The confirmation of the eligibility criteria is followed by a roll-in phase of approximately 6 months. At the end of the roll-in period, Holoclar will be implanted through a specific surgical procedure.

After ACLSCT, efficacy assessments will be performed at 1, 3, 6, 9 and 12 months for both first and second treatment (the latter only when applicable). One year after the transplantation, efficacy will be adjudicated by two independent assessors (primary and key secondary endpoints) and the study completion will be reached when 1 year of follow-up after the last transplant in the last patient will be accomplished.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : October 2015
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Burns

Arm Intervention/treatment
Experimental: Holoclar
Treatment with Holoclar (medicinal product), including biopsy, graft production and implantation of the graft containing stem cell
Procedure: Biopsy from donor eye
Corneal biopsy from undamaged limbus

Procedure: Implant of Holoclar
Implant of Holoclar into the eye to be treated after scraping of the fibrovascular pannus
Other Name: ACLSCT

Procedure: Ophtalmologic examination

The following assessments are performed:

Epithelial defects assessment by fluorescein staining; superficial corneal neo-vascularization assessment; Best-Corrected Visual Acuity; ocular tonometry; slit lamp examination (both corneal endothelium and anterior chamber); conjunctival inflammation (both bulbar and limbal) assessment; corneal sensitivity and involvement assessment; Schirmer's test type I; evaluation of the following symptoms: pain, burning, photophobia.


Procedure: Blood sample collection
Standard haematology, biochemistry and Infectious profile (Virology) are assessed

Procedure: Digital pictures
At least 4 digital corneal slit lamp photos without fluorescein and at least 4 digital corneal slit lamp photos with fluorescein are taken using digital camera

Procedure: ECG
A 12-lead ECG measurement in single recording at screening for safety reason and before each transplantation.

Behavioral: Questionnaires
Quality of Life assessment through the NEI VFQ 25and EQ-5D-3L questionnaire (EQ-5D-Y in paediatric population)

Procedure: Physical examination and vital signs
A complete physical examination and vital signs (Systolic and Diastolic Blood Pressure (SBP, DBP) and Pulse Rate (PR) must be assessed at each visit (but not at pre-screening and at visit 6)




Primary Outcome Measures :
  1. Success of transplantation [ Time Frame: 12 months after 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".


Secondary Outcome Measures :
  1. Success of one or two transplantation(s) [ Time Frame: 12 months after the last transplantation ]

    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.




Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02577861


Contacts
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Contact: Clinical Trial Info +39.0521 2791 clinicaltrials_info@chiesi.com

Locations
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Italy
Hospital San Raffaele Recruiting
Milan, Italy, 20100
Contact: Paolo Rama, MD         
Contact: Fania Ferrari, BSc         
Sponsors and Collaborators
Chiesi Farmaceutici S.p.A.
Investigators
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Study Chair: Federica Cattaneo, MD Chiesi Farmaceutici SpA
Principal Investigator: Paolo Rama, MD Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele

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Responsible Party: Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier: NCT02577861     History of Changes
Other Study ID Numbers: CCD-GPLSCD01-03
2014-002845-23 ( EudraCT Number )
First Posted: October 16, 2015    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Chiesi Farmaceutici S.p.A.:
limbal stem cells deficinecy, LSCD, ocular burn