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AzTrials

Limbal Stem Cells DeficiencyPhase 4HOLOCORENCT02577861

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

A Phase 4 study testing Biopsy from donor eye, Implant of Holoclar and Ophtalmologic examination in people with Limbal Stem Cells Deficiency, run by Holostem s.r.l. at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 years and older
Conditions the study is for
Limbal Stem Cells Deficiency
What is being tested?
Biopsy from donor eye, Implant of Holoclar and Ophtalmologic examination
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteItaly
Study dates
Oct 2015to 11 Mar 2022
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
  • 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;
  • 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).

Who cannot join

  • 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;
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  • 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;
  • 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;
  • 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.
  • Participation in another clinical trial where investigational drug was received less than 4 weeks prior to screening visit.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Hospital San Raffaele

    Milan, 20100

Other trials in Italy

About this study

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)

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.

Read the 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.

Being tested
Biopsy from donor eye, Implant of Holoclar, Ophtalmologic examination, Blood sample collection, Digital pictures
Keywords
limbal stem cells deficinecy, LSCD, ocular burn

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy from donor eyeProcedure or surgery

    Corneal biopsy from undamaged limbus

  • Implant of HoloclarProcedure or surgery

    Also called ACLSCT

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

  • Ophtalmologic examinationProcedure or surgery

    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.

  • Blood sample collectionProcedure or surgery

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

  • Digital picturesProcedure or surgery

    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

  • ECGProcedure or surgery

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

  • QuestionnairesBehavioural

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

  • Physical examination and vital signsProcedure or surgery

    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)

Study groups in NCT02577861
Study groupRoleWhat they receive
HoloclarExperimentalTreatment with Holoclar (medicinal product), including biopsy, graft production and implantation of the graft containing stem cell
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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".

    Measured: 12 months after transplantation

Secondary outcomes (1)

  1. 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.

    Measured: 12 months after the last transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2015 (estimated)
  2. Study startOct 2015
  3. Primary completionDec 2020
  4. Study completion11 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02577861
Sponsor's protocol ID
CCD-GPLSCD01-03
Other IDs
2014-002845-23, 2014
Acronym
HOLOCORE
Status last verified
Mar 2022
First submitted
15 Oct 2015
Last updated
1 Apr 2022
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Biopsy from donor eye, Implant of Holoclar and Ophtalmologic examination in people with Limbal Stem Cells Deficiency, run by Holostem s.r.l. at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Success of transplantation (time frame: 12 months after transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02577861.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2022.

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