A clinical study to follow the implantation of Holoclar on the cornea in patients with occular burns

• Register: EUCTR
• Last refreshed on: 30 November 2020
• Main ID: EUCTR2014-002845-23-PL
• Date of registration: 30/09/2015
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: A clinical study to follow the implantation of Holoclar on the cornea in patients with occular burns
• Scientific 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
• Date of first enrolment: 26/10/2015
• Target sample size: 92
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002845-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: prospective trial If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Belgium, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom

Contacts

• Name: Clinical Project Manager
• Affiliation: Chiesi Farmaceutici S.p.A.

• Name: Clinical Project Manager
• Affiliation: Chiesi Farmaceutici S.p.A.

Key inclusion & exclusion 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 evidence of central corneal (central 6 mm
diameter) involvement (including central corneal neo-vascularisation or
corneal opacity) according to the independent assessors;
4. Stability of LSCD, defined by a duration of disease of at least 24
months (12 months for minors) at the time of the Screening Visit and as
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
after best correction (i.e. Best Corrected Visual Acuity) equal or below
1/10 (or 20/200) at the Snellen chart (legal blindness);
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).
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 73
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion criteria:
1. LSCD of mild degree (i.e. below 2 quadrants of vascularization
invasion), due to a recent burn (less than 24 months before screening
for adults and 12 months for minors), 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. Tear secretion deficiency, determined by Schirmer’s test (<5 mm/ 5 min);
6. Corneal anaesthesia and conjunctival anaesthesia or severe hypoesthesia;
7. 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 (i.e. use of contrast medium in the
last two weeks) or any other invasive procedure which could
affect the integrity of the epithelium


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

corneal lesions with associated moderate to severe limbal stem cell deficiency due to ocular burns
MedDRA version: 20.0 Level: LLT Classification code 10011012 Term: Corneal epithelium opacity System Organ Class: 100000004853

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Intervention(s)

Trade Name: HOLOCLAR
Product Name: Holoclar
Pharmaceutical Form: Living tissue equivalent
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: CCD-GPLSCD01-03
Other descriptive name: EX VIVO EXPANDED AUTOLOGOUS HUMAN CORNEAL EPITHELIAL CELLS CONTAINING STEM CELLS
Concentration unit: cm2 square centimeter
Concentration type: equal
Concentration number: 3.8-

Primary Outcome(s)

Secondary Objective: To evaluate the efficacy of one or two treatments with Holoclar at one year after the last treatment.

Primary end point(s): - Percentage of patients with a success of transplantation (success is defined on the basis of the degree of “superficial corneal neo-vascularization” and “epithelial defects”)

Main Objective: To demonstrate the efficacy of Holoclar® at one year after the first
treatment in patients suffering from moderate (vascularization in two-three
corneal quadrants with central corneal involvement) to severe
(vascularization in four corneal quadrants with central corneal
involvement) LSCD with severe visual impairment and secondary to
ocular burns, in terms of percentage of patients with a success of
transplantation at approximately 12 months from the first Holoclar®
treatment.

Timepoint(s) of evaluation of this end point: 12 months from the first Holoclar treatment

Secondary Outcome(s)

Secondary end point(s): - Percentage of patients with clinical success after one or two ACLSCTs (same definition of success as primary endpoint)

Timepoint(s) of evaluation of this end point: 12 months after the last treatment with Holoclar.

Secondary ID(s)

CCD-GPLSCD01-03

2014-002845-23-DE

Source(s) of Monetary Support

Chiesi Farmaceutici S.p.A.

Ethics review

Status: Approved
Approval date: 28/09/2015
Contact: