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Allogeneic ABCB5-positive Limbal Stem Cells for Treatment of LSCD

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ClinicalTrials.gov Identifier: NCT03549299
Recruitment Status : Not yet recruiting
First Posted : June 8, 2018
Last Update Posted : January 28, 2019
Sponsor:
Collaborators:
FGK Clinical Research GmbH
Ticeba GmbH
Granzer Regulatory Consulting & Services
Information provided by (Responsible Party):
RHEACELL GmbH & Co. KG

Brief 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. Further, safety of the IMP during and after application will be investigated (by monitoring adverse events [AEs]).

Condition or disease Intervention/treatment Phase
Limbal Stem Cell Deficiency Biological: LSC2 Phase 1 Phase 2

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 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be treated in up to four ascending dose groups. After the last treated patient of the first dose group (Group A) was followed for 6 weeks, a safety and tolerability assessment of the applied IMP dose will be conducted by an internal committee. 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. The same approach applies to Group C and D.
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : February 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2021

Arm Intervention/treatment
Experimental: LSC2; 7.5 x 10^4 cells
Single dose of LSC2, 7.5 x 10^4 cells per patient
Biological: LSC2
Topical application of IMP on target eye
Other Name: Suspension of ABCB5-positive limbal stem cells in pre-filled syringe

Experimental: LSC2; 3.0 x 10^5 cells
Single dose of LSC2, 3.0 x 10^5 cells per patient
Biological: LSC2
Topical application of IMP on target eye
Other Name: Suspension of ABCB5-positive limbal stem cells in pre-filled syringe

Experimental: LSC2; 8.0 x 10^5 cells
Single dose of LSC2, 8.0 x 10^5 cells per patient
Biological: LSC2
Topical application of IMP on target eye
Other Name: Suspension of ABCB5-positive limbal stem cells in pre-filled syringe

Experimental: LSC2; 1.2 x 10^6 cells
Single dose of LSC2, 1.2 x 10^6 cells per patient
Biological: LSC2
Topical application of IMP on target eye
Other Name: Suspension of ABCB5-positive limbal stem cells in pre-filled syringe




Primary Outcome Measures :
  1. Response rate at 12 months after IMP application [ Time Frame: Month 12 ]

    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)

  2. Assessment of adverse event (AE) occurrence [ Time Frame: Up to 24 months. ]
    All AEs occurring during the clinical trial will be registered, documented and evaluated.


Secondary Outcome Measures :
  1. Response rate at 3 months after IMP application [ Time Frame: Month 3 ]

    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)

  2. Neovascularization [ Time Frame: Baseline, week 1, 2, 3, 4, 5, 6, 7, month 3, 6 and 12 ]
    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).

  3. Epithelial defects [ Time Frame: Baseline, week 2, 4, 6, month 3, 6 and 12 ]
    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.

  4. Ocular symptoms of pain, photophobia, burning [ Time Frame: Baseline, week 2, 4, 6, month 3, 6 and 12 ]

    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).


  5. Ocular inflammation [ Time Frame: Baseline, week 2, 4, 6, month 3, 6 and 12 ]
    The assessment of inflammation will be categorized as present (yes) or nonexistent (no).

  6. Corneal opacity [ Time Frame: Baseline, week 2, 4, 6, month 3, 6 and 12 ]

    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)

  7. Visual acuity [ Time Frame: Baseline, week 2, 4, 6, month 3, 6 and 12 ]
    Clarity of vision.

  8. Quality of life [ Time Frame: Baseline, month 3 and 12 ]
    Quality of life (visual function questionnaire-25 [VFQ-25]) questionnaire to be answered.

  9. Physical examination [ Time Frame: Baseline, month 3 and 12 ]
    A full physical examination will be performed at week 12 and abnormal physical examination results will be evaluated and reported as AEs.

  10. Tonometry [ Time Frame: Baseline,week 1, 3, 7 and Month 3 ]
  11. Vital signs: Body temperature at Baseline, month 3 and 12 [ Time Frame: Baseline, month 3 and 12 ]
    Body temperature at Baseline, month 3 and 12 will be evaluated.

  12. Vital signs: Blood pressure at Baseline, month 3 and 12 [ Time Frame: Baseline, month 3 and 12 ]
    Blood pressure at Baseline, month 3 and 12 will be evaluated.

  13. Vital signs: Heart rate at Baseline, month 3 and 12 [ Time Frame: Baseline, month 3 and 12 ]
    Heart rate at Baseline, month 3 and 12 will be evaluated.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. Compromised eyelid mobility and/or symblepharon; patient can be re-screened after appropriate treatment
  2. Presence of eyelid malposition; patient can be re-screened after appropriate treatment
  3. Active local ocular or systemic infection and/or inflammation. Patient can be re-screened after infection and/or inflammation is resolved.
  4. Tumor diseases or history of tumor disease
  5. Active ocular neoplastic disease (exclusion will be based on investigator's assessment)
  6. 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).
  7. Positive for human immunodeficiency virus (HIV) 1 and/or 2 (diagnosed by serologic testing)
  8. Any known allergies to components of the IMP or per protocol pre-planned concomitant medications
  9. Contraindications to the surgical procedure (e.g. removing of the conjunctival pannus)
  10. Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell transplantation
  11. Further clinical contraindications to IMP application (exclusion will be based upon investigator's judgment)
  12. Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial
  13. 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)
  14. Known abuse of alcohol, drugs, or medicinal products
  15. Patients unwilling or unable to comply with the requirements of the protocol
  16. Lactating women
  17. 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
  18. Employees of the sponsor, or employees or relatives of the investigator

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): NCT03549299


Contacts
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Contact: Christoph Ganss, Dr. med +49 6221 71833 ext 0 office@rheacell.com
Contact: Ulf Dehio +49 6221 71833 ext 0 ulf.dehio@rheacell.com

Locations
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United States, Massachusetts
Massachusetts Eye and Ear Infirmary Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: James Chodosh, MD, MPH         
Germany
Universitäts-Klinikum Heidelberg, Kopfklinik Not yet recruiting
Heidelberg, Germany, 69120
Contact: Gerd U. Auffarth, Prof. Dr. med.         
Universitäts-Klinikum Jena, Augenklinik Not yet recruiting
Jena, Germany, 07747
Contact: Daniel Meller, Prof. Dr. med.         
Universitäts-Klinikum Köln, Augenklinik Not yet recruiting
Köln, Germany, 50937
Contact: Claus Cursiefen, Prof. Dr. med.         
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Augenklinik und Poliklinik Not yet recruiting
Mainz, Germany, 55131
Contact: Norbert Pfeiffer, Prof. Dr. med         
Sponsors and Collaborators
RHEACELL GmbH & Co. KG
FGK Clinical Research GmbH
Ticeba GmbH
Granzer Regulatory Consulting & Services
Investigators
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Principal Investigator: Gerd U. Auffarth, Prof. Dr. med. Universitäts-Klinikum Heidelberg, Kopfklinik, Heidelberg, Germany

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Responsible Party: RHEACELL GmbH & Co. KG
ClinicalTrials.gov Identifier: NCT03549299     History of Changes
Other Study ID Numbers: LSC2-II-01
First Posted: June 8, 2018    Key Record Dates
Last Update Posted: January 28, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by RHEACELL GmbH & Co. KG:
limbal stem cell deficiency
ABCB5
Limbal stem cells
LSCs
LSC
allogeneic
tissue engineered product
phase I/IIa