Exploratory clinical study to examine safety and efficacy of iPS cell-derived corneal endothelial cell substitutes for bullous keratopathy (CLS001)
iPS cell-derived corneal endothelial cell substitutes for bullous keratopathy (CLS001)
Morio Matsumoto
Hirayama Masatoshi
Keio University
35 Shinanomachi,Shinjuku-ku,Tokyo
+81-3-3353-1211
keio_clinicalstudy347@googlegroups.com
Saiki Mieko
Keio University
35shinanomachi,shinjuku-ku,tokyo, Japan
+81-3-3353-1211
keio_clinicalstudy347@googlegroups.com
3
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
1) A diagnosis of bullous keratopathy after corneal transplantation, including at least one previous penetrating keratoplasty.
2) Forty five years of age or older and under 85 years of age at the time of consent acquisition (male or female)
3) A central corneal endothelial cell density of less than 500 cells/mm^2 measured by specular microscope or confocal microscope, or undetactable.
4) Voluntary written consent to participate in the study.
1) Patients with undiagnosed keratoconjunctival disease.
2) Central corneal thickness of 1200 micro meter or blood vessel invasion in the stroma of cornea.
3) i) Active corneal infection OR ii) Active systemic infections (bacteria, fungi, positive in viral test such as hepatitis B virus, hepatitis C virus, etc.).
4) IOP >= 30 mmHg or even with glaucoma drugs administration IOP >= 21 mmHg
5) Diabetes that it difficult to control(HbA1C 8.0% or higher).(This can be omitted in the primary verification of eligibility.)
6) Neovascularization in the iridocorneal angle or after neovascular glaucoma treatment.
7) Medical history of hypersensitivity to anesthetic(xylocaine injection solution), antibiotics(levofloxacin ophthalmic solution),steroids(sanbetason ophthalmic and otorhinologic solution 0.1%, flumetholon ophthalmic suspension 0.1%),glaucoma treatment(prostaglandin analog, beta inhibitor,azopt otorhinologic solution, glanatec otorhinologic solution and so on),used during perioperative and postoperative observation.
8) Scheduled to undergo internal eye surgery during the study.
9) Medical history of cancer
10) Presence of significant hepatic failure (with either AST or ALT higher than 100 IU/L).(This can be omitted in the primary verification of eligibility.)
11) Presence of renal failure requiring dialysis(serum creatinine level 1.5 mg/dl or higher).(This can be omitted in the primary verification of eligibility.)
12) Systolic blood pressure of 180 mmHg or higher, or diastolic blood pressure of 110 mmHg or higher, even with antihypertensive drug.
13) Not consent to contraception or hopes his partner's pregnancy during the study.
14) Cannot endure ophthalmic surgery under local anesthesia (Extreme claustrophobia, etc.).
15) Participation in other clinical trials one month prior to when informed consent is obtained
16) Other cases where the principal investigator or sub investigator decides the subject is unsuitable for the study.
*1 : The following items refer to transplanted eyes. 1)-4), 6)and 8).
*2 : These tests examine the patient's blood type and HLA gene type during screening. The results are not used to determine exclusion criteria, regardless of whether his or her blood type or HLA type matches that of the iPS cell donor.
45age old over
85age old under
Both
Bullous keratopathy
D064987
Cell Therapy
The number of subjects was planned to be the minimum necessary to confirm the trend and reproducibility in safety of iPS cell-derived corneal endothelial cell substitutes for bullous keratosis, to explore its efficacy, and to provide base data for future clinical trial planning.
Topical anesthesia eyedrop and injection of local anesthesia into the sub conjunctival space. Marking the central cornea with an 8 mm circular marker with blue pigment. Paracentesis through the limbus into the anterior chamber and maintaining its space by viscoelastic material. Inserting a 20G soft tapered needle for eye surgery through the wound to scrape off the corneal endothelial cells within the range not exceeding the circumference of 8 mm diameter marked area. Staining of the anterior chamber with ophthalmic surgery aid VISION BLUE to check the area of endothelial loss. After washing the anterior chamber with perfusion solution for ophthalmic surgery, the wound is sutured by 10-0 nylon thread. Filling the iPS cell-derived corneal endothelium substitute cells (CLS001) suspension from the tube into a medical syringe using a micro pipet. The tip of the syringe containing CLS001 suspension is punctured into the anterior chamber, and the target quantity of cell CLS001 suspension is injected.
After cell injection, patients were fixed in the face-down position for three hours so that the cells can settle and adhere to the posterior surface of cornea.
D015715
Edema, corneal
<Safety endpoint>
1) safety endpoint (systemic)
All adverse events, including systemic symptoms
2) safety endpoint (ophthalmologic)
[The following adverse events caused by iPS cell-derived corneal endothelium substitute cells]
- Unintended cell proliferation
- Increased intraocular pressure
- Rejection reaction
[The following adverse events resulting from transplant surgery and procedures]
- Infectious disease
- Cataract progression
- Expulsive Hemorrhage
