To establish the safety and tolerability of two intravenous infusions of allo-hBM-MSC or stromal cell therapy at 7 and 1 days prior to the performance of a corneal re-transplantation procedure.
To evaluate the potential effect of pre-transplant intravenous infusions of allo-hBM-MSC or stromal cell therapy to reduce the risk of acute rejection of corneal re-transplants.
To evaluate the potential effect of pre-transplant intravenous infusions of allo-hBM-MSC or stromal cell therapy on physiology and functional parameters of the transplant.
Prospective, single-centre, open-label, phase Ib trial of systemic allo-hBM-MSC or stromal cell therapy in high-risk corneal transplant patients undergoing full-thickness corneal re-transplantation:
The study will include two cohorts consisting of 4 study patients each. The first cohort of 4 patients will receive a low dose regimen (2 infusions of 80 million cells each). If the initial safety profile of the first dose cohort meets the dose-escalation rules, the second cohort of 4 patients will then be assigned to the higher dose regimen (2 infusions of 160 x million cells each). The study is composed of a screening and enrolment period (Visit 1: Days -28 to -14), a treatment period including the two infusions of allo-hBM-MSC on Visit 2 (Day -7) and Visit 3 (Day -1) prior to the scheduled corneal re-transplantation procedure. The full-thickness corneal re-transplantation will be performed on Visit 4 (Day 1).
Cell infusions and post-infusion monitoring (Visits 2 and 3) will be carried out in the clinical research facility. After corneal transplantation, patients in both cohorts will return to the research facility for a total of five post-transplant follow-up visits on Days +7, +14, +28, +56 and Day 84 The final visit for assessment of the primary endpoint will take place at Visit 9 (Day 84).
A Drug Safety Monitoring Board (DSMB) will continuously monitor trial safety. The duration of follow-up after the corneal transplant will be 12 weeks. Continuity of patient care after the end of study (EOS) includes treatment according to local guidelines and standard of care. Patient data will be recorded as part of routine medical care up to 12 months after EOS.