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

NCT02577861 | Completed Phase 4

• 2 other identifiers: CCD-GPLSCD01-032014-002845-23
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Limbal Stem Cells Deficiency

Keywords

limbal stem cells deficinecy, LSCD, ocular burn

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Success of one or two transplantation(s)

  12 months after the last transplantation

Study Arms (1)

Holoclar

EXPERIMENTAL

Treatment with Holoclar (medicinal product), including biopsy, graft production and implantation of the graft containing stem cell

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

Interventions

Biopsy from donor eye PROCEDURE

Corneal biopsy from undamaged limbus

Holoclar

Implant of Holoclar PROCEDURE

Implant of Holoclar into the eye to be treated after scraping of the fibrovascular pannus

Also known as: ACLSCT

Holoclar

Ophtalmologic examination PROCEDURE

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.

Holoclar

Blood sample collection PROCEDURE

Standard haematology, biochemistry and Infectious profile (Virology) are assessed

Holoclar

Digital pictures PROCEDURE

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

Holoclar

ECG PROCEDURE

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

Holoclar

Questionnaires BEHAVIORAL

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

Holoclar

Physical examination and vital signs PROCEDURE

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)

Holoclar

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent prior to any study-related procedures.
• Adult male and female patients (≥18 years old); Five Paediatric patients aged 2 to 17 years will be also enrolled for safety purposes only.
• 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.
• 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);
• Absence of other clinical contraindications to ACLSC transplantation based upon investigator's judgment;
• A cooperative attitude to follow up the study procedures (Caregivers in case of minors).

You may not qualify if:

• 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);
• Severe ocular inflammation according to the Efron Grading Scale for Contact Lens Complications. Patient can be re-screened after appropriate treatment;
• Presence of eyelids malposition;
• Conjunctival scarring with fornix shortening;
• Severe tear secretion deficiency, determined by Schirmer's test type I (\<5 mm/ 5 min);
• Corneal anaesthesia and conjunctival anaesthesia;
• Active local or systemic infections at the time of screening. Patient can be re-screened after appropriate treatment;
• Diagnosis of local or systemic neoplastic disease;
• Congenital diseases (i.e., Aniridia);
• Bilateral inflammatory diseases (i.e. Stevens-Johnson syndrome, phemphigoid);
• A pre-existing blindness precluding a functional recovery;
• 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.
• 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);
• Contraindications to the local or systemic antibiotics and/ or corticosteroids foreseen by the protocol;
• Contraindications to the surgical procedure;

Sponsors & Collaborators

• Holostem s.r.l.: lead

Study Sites (1)

Hospital San Raffaele

Milan, 20100, Italy

Location

MeSH Terms

Interventions

Surveys and Questionnaires; Restraint, Physical

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Behavior Control; Therapeutics; Immobilization

Study Officials

• Graziella Pellegrini, Professor

  Holostem s.r.l.

  STUDY DIRECTOR

• Paolo Rama, MD

  Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2015
• First Posted: October 16, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2020
• Study Completion: March 11, 2022
• Last Updated: April 1, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)