Testing for safety and efficacy is required before any new medical intervention can enter routine use. Such clinical research takes various forms that differ in the number of human research subjects and features of the study design. In Japanese law, two main types of clinical experiments are recognized: registered clinical trials, which are used to test medical products prior to market authorization, and general clinical research, which includes smaller-scale studies, such as the pilot study described in this website, and evaluations of some medical procedures, such as surgical techniques.
The research plan introduced in this website is for an open-label study of the transplantation of autologous induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) cell sheets in patients with exudative age-related macular degeneration (AMD). This is a very early-stage form of clinical research, and is intended to assess the safety of this intervention; it is not expected to yield significant improvements in visual acuity or other symptoms in the patients who participate in the study.
1) The current study is designed to evaluate this intervention only in patients with the exudative (wet-type) form of age-related macular degeneration.
2) The primary outcome to be assessed in this study is the safety of the intervention. If it is found to be acceptably safe, future studies will evaluate its efficacy. Patients who participate in this pilot study are not expected to experience dramatic improvements in their symptoms.
3) Enrolment in the study is limited to six subjects, as the safety of the intervention has not been established.
4) This pilot study is a very early stage of clinical research into the use of an iPSC-based intervention. Even in the event that this study suggests the intervention is acceptably safe to proceed to subsequent stages, a great deal of further research, including full-scale clinical trials, will be needed to more thoroughly evaluate the safety and efficacy of this approach.
In the first stage of the study, a 4 mm biopsy of tissue will be collected from the skin of each subject’s upper arm and cultured in a cell processing center. The skin cells will then be used to generate induced pluripotent stem cells (iPSCs). The autologous iPSCs will next be differentiated in culture into monolayer ‘sheets’ of retinal pigment epithelium (RPE) suitable for transplantation. The entire process, including regular assessments of safety and quality, will require approximately 10 months for each patient.
Once complete, the RPE cell sheets will be transplanted into the affected site in a single eye, from which the neovascular tissue has first been removed. Subjects will be monitored and followed up for four years following transplantation.