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Limbal Stem Cell DeficiencyPhase 1/2NCT03549299

Allogeneic ABCB5-positive Limbal Stem Cells for Treatment of LSCD

A Phase 1/2 study testing LSC2 in people with Limbal Stem Cell Deficiency, run by RHEACELL GmbH & Co. KG at 5 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The aim of this clinical trial is to investigate the efficacy (by monitoring neovascularization and epithelial defects) of up to four doses of the investigational medicinal product (IMP) LSC2 topically administered on the target eye of patients with LSCD. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Limbal Stem Cell Deficiency
What is being tested?
LSC2
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
5 sitesin 2 countries
Study dates
4 Jul 2019to Sep 2023
Phase
Phase 1/2
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 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients aged 18 to 85 years
  • Patients with secondary bilateral or unilateral LSCD (injury that caused LSCD at least 6 months prior to inclusion)
  • Neovascularization: Vessel penetration of at least 2 quadrants, with central cornea involved
  • Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure
  • Women of childbearing potential must have a negative blood pregnancy test at Visit 1
  • Women of childbearing potential must be willing to use highly effective contraceptive methods during the course of the clinical trial

Who cannot join

  • Compromised eyelid mobility and/or symblepharon; patient can be re-screened after appropriate treatment
  • Presence of eyelid malposition; patient can be re-screened after appropriate treatment
  • Active local ocular or systemic infection and/or inflammation. Patient can be re-screened after infection and/or inflammation is resolved.
  • Tumor diseases or history of tumor disease
  • Active ocular neoplastic disease (exclusion will be based on investigator's assessment)
  • Corneal erosion or ulcer is bigger than 4 mm2; corresponding to less than 95% of continuous corneal epithelium. Patient can be re-screened after erosion or ulcer is resolved (≤ 4 mm2).
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  • Positive for human immunodeficiency virus (HIV) 1 and/or 2 (diagnosed by serologic testing)
  • Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell transplantation
  • History of glaucoma
  • Contraindications to trial related procedures/substances including
  • The surgical procedure (e.g. removing of the conjunctival pannus)
  • Contact lens complications due to contact lens use in the proposed trial (based on the Efron Grading scale for standard clinical reference for contact lens complications)
  • Tear secretion deficiency determined by Schirmer's test
  • Allergy, sensitivity or intolerance to components/excipients of the IMP/ per protocol pre-planned concomitant medications
  • Conjunctival scarring with fornix shortening
  • General anesthesia (in case general anesthesia is required) or local anesthesia
  • Immunosuppression (being mandatory concomitant therapy)
  • Intraocular pressure (IOP) of ≥30 mm Hg
  • History or clinical signs of stroke or transient ischemic attacks
  • Active or suspected ocular or periocular infections
  • Active or suspected intraocular inflammation
  • Further clinical contraindications to IMP application (exclusion will be based upon investigator's judgment)
  • Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial
  • Previous participation in this clinical trial (except screening failure due to inclusion criterion 2 and/or exclusion criterion 1 and/or 2 and/or 3 and/or 6)
  • Known abuse of alcohol, drugs, or medicinal products
  • Patients unwilling or unable to comply with the requirements of the protocol
  • Lactating women
  • Evidence of any other medical conditions (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the patient's compliance, or place the patient at high risk of complications related to the treatment
  • Employees of the sponsor, or employees or relatives of the investigator

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

Germany4 sites

  • Universitäts-Klinikum Köln, Augenklinik

    Cologne, 50937

  • Universitäts-Klinikum Heidelberg, Kopfklinik

    Heidelberg, 69120

  • Universitäts-Klinikum Jena, Augenklinik

    Jena, 07747

  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Augenklinik und Poliklinik

    Mainz, 55131

Other trials in Germany

United States1 site

  • Massachusetts Eye and Ear Infirmary

    Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: An Interventional, Open-label, Multicenter Phase I/IIa Clinical Trial to Investigate the Safety and Efficacy of Ascending Doses of Allogeneic ABCB5-positive Limbal Stem Cells (LSC2) for the Treatment of Limbal Stem Cell Deficiency (LSCD)

The aim of this clinical trial is to investigate the efficacy (by monitoring neovascularization and epithelial defects) of up to four doses of the investigational medicinal product (IMP) LSC2 topically administered on the target eye of patients with LSCD. Further, safety of the IMP during and after application will be investigated (by monitoring adverse events [AEs]).

Read the detailed description

This is an interventional, open-label, phase I/IIa clinical trial to investigate the efficacy and safety of up to four doses of the IMP topically administered on the target eye of patients with LSCD. Patients will be treated in up to four ascending dose groups.

The allogeneic investigational product LSC2 contains ABCB5-positive limbal stem cells (from corneal rims of cadaveric donors, expanded ex vivo, isolated and stored in a donor cell bank).

The IMP will be applied on the target eye. Prior to application, the conjunctival pannus will be removed under general or local anesthesia.

Patients will be followed up for efficacy for 1 year. Efficacy of the IMP will be monitored by assessing neovascularization and epithelial defects.

To assess long-term safety of LSC2 one follow-up visit at Month 24 post IMP application is included.

Being tested
LSC2
Keywords
limbal stem cell deficiency, ABCB5, Limbal stem cells, LSCs, LSC, allogeneic, tissue engineered product, phase I/IIa
Medical subject headings
Limbal Stem Cell Deficiency

What participants receive

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

  • LSC2Biological

    Also called Suspension of ABCB5-positive limbal stem cells in pre-filled syringe

    Topical application of IMP on target eye

Study groups in NCT03549299
Study groupRoleWhat they receive
LSC2; 7.5 x 10^4 cellsExperimentalSingle dose of LSC2, 7.5 x 10^4 cells per patient
Receives: Biological: LSC2
LSC2; 3.0 x 10^5 cellsExperimentalSingle dose of LSC2, 3.0 x 10^5 cells per patient
Receives: Biological: LSC2
LSC2; 8.0 x 10^5 cellsExperimentalSingle dose of LSC2, 8.0 x 10^5 cells per patient
Receives: Biological: LSC2
LSC2; 1.2 x 10^6 cellsExperimentalSingle dose of LSC2, 1.2 x 10^6 cells per patient
Receives: Biological: LSC2

What is being measured

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

  1. Response rate at 12 months after IMP application

    Response rate at 12 months after IMP application, where response is defined as:

    • no or mild corneal neovascularization (no vessel penetration or vessel penetration up to 1 quadrant, without central cornea) AND
    • no or mild epithelial defects (no corneal erosion or ulcer are present (corneal wounds are closed) or minimal superficial staining)

    Measured: Month 12

  2. Assessment of adverse event (AE) occurrence

    All AEs occurring during the clinical trial will be registered, documented and evaluated.

    Measured: Up to 24 months.

Secondary outcomes (13)

  1. Response rate at 3 months after IMP application

    Response rate at 3 months after IMP application, where response is defined as:

    • no or mild corneal neovascularization (no vessel penetration or vessel penetration up to 1 quadrant, without central cornea) AND
    • no or mild epithelial defects (no corneal erosion or ulcer are present (corneal wounds are closed) or minimal superficial staining)

    Measured: Month 3

  2. Neovascularization

    Corneal neovascularization will be assessed as "none" (no blood vessel penetration), "mild" (blood vessel penetration of 1 quadrant, without central cornea involvement), "moderate" (blood vessel penetration of 1 quadrant, with central cornea involvement or blood vessel penetration of 2 or 3 quadrants, with or without central cornea involvement) or "strong" (blood vessel penetration of all quadrants, with or without central cornea involvement).

    Measured: Baseline, week 1, 2, 3, 4, 5, 6, 7, 12, month 6 and 12

  3. Epithelial defects

    Epithelial defects will be assessed as "none" (no corneal erosion or ulcer are present (corneal wounds are closed)) or "mild" (minimal superficial staining) or "moderate" (dense coalescent staining up to 2 mm in diameter) or "strong" (dense coalescent staining greater than 2 mm in diameter) by means of fluorescein staining.

    Measured: Baseline, week 2, 4, 6, month 3, 6 and 12

  4. Ocular symptoms of pain, photophobia, burning

    Photophobia and burning will be assessed as "no complaint" (grade 0), "mild" (grade 1), "moderate" (grade 2) or "severe" (grade 3).

    Pain assessment will be done by the patient using a 11-point numerical rating scale ranging between no pain (zero) and worst imaginable pain (ten).

    Measured: Baseline, week 2, 4, 6, 12, month 6 and 12

  5. Ocular inflammation

    The assessment of inflammation will be categorized as present (yes) or nonexistent (no).

    Measured: Baseline, week 2, 4, 6, 12, month 6 and 12

  6. Corneal opacity

    Corneal opacification will be assessed as "none" (no corneal opacification), "mild" (corneal opacification in up to 1 quadrant, without central cornea involvement), "moderate" (corneal opacification in 1 quadrant, with central cornea involvement or corneal opacification in 2 or 3 quadrants, with or without central cornea involvement) or "strong" (corneal opacification in all quadrants, with or without central cornea involvement).

    Additional densitometric Pentacam® measurements are optional. Opacity values of the following ring-shaped corneal segments will be record:

    • 0 - 2 mm, 2 - 6 mm, 6 - 10 mm, 10 - 12 mm (anterior, central and posterior corneal layer for each segment)
    • 0 - 2 mm, 2 - 6 mm, 6 - 10 mm, 10 - 12 mm (full thickness average for each segment)
    • Anterior layer of the complete cornea (0 - 12 mm)
    • Central layer of the complete cornea (0 - 12 mm)
    • Posterior of the complete cornea (0 - 12 mm)
    • Overall cornea (0 - 12 mm, full thickness)

    Measured: Baseline, week 2, 4, 6, 12, month 6 and 12

  7. Visual acuity

    Clarity of vision.

    Measured: Baseline, week 2, 4, 6, 12, month 6 and 12

  8. Quality of life assessment

    Quality of life (visual function questionnaire-25 [VFQ-25]) questionnaire to be answered.

    Measured: Baseline, week 12, month 12

  9. Physical examination

    A full physical examination will be performed at week 12 and abnormal physical examination results will be evaluated and reported as AEs.

    Measured: Baseline, week 12, month 12

  10. Tonometry

    Measured: Baseline,week 1, 3, 7 and 12

  11. Vital signs: Body temperature at Baseline, week 12, month 12

    Body temperature at Baseline, week 12 and month 12 will be evaluated.

    Measured: Baseline, week 12, month 12

  12. Vital signs: Blood pressure at Baseline, week 12, month 12

    Blood pressure at Baseline, week 12 and month 12 will be evaluated.

    Measured: Baseline, week 12, month 12

  13. Vital signs: Heart rate at Baseline, week 12, month 12

    Heart rate at Baseline, week 12 and month 12 will be evaluated.

    Measured: Baseline, week 12, month 12

Timeline

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

  1. First posted8 Jun 2018
  2. Study start4 Jul 2019
  3. Primary completionSep 2023 (estimated)
  4. Study completionSep 2023 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Patients will be treated in up to four ascending dose groups. After the first treated patient of the first dose group (Group A) was followed for 2 weeks, a safety and tolerability assessment of the applied IMP dose will be conducted by an internal committee. The same approach applies to the second subject. Dose escalation and recruitment of additional patients into the second dose group (Group B) will depend on the safety and tolerability of the IMP in Group A. A safety and tolerability assessment will be conducted after the last treated patient of the first dose group (Group A) was followed for 12 weeks. The same approach applies to Group C and D.
Masking
None (open label)
Enrolment
16 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03549299
Sponsor's protocol ID
LSC2-II-01
Status last verified
Oct 2022
First submitted
14 May 2018
Last updated
7 Oct 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LSC2 in people with Limbal Stem Cell Deficiency, run by RHEACELL GmbH & Co. KG at 5 sites in 2 countries.

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 6 inclusion and 29 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: status not confirmed, as of the sponsor's last update on 7 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Germany, United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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?

Response rate at 12 months after IMP application (time frame: Month 12). The study lists 2 primary outcomes in all. 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 NCT03549299.

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 7 Oct 2022.

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