OpRegen for Age-Related Macular Degeneration
Recruiting in Palo Alto (17 mi)
+9 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Genentech, Inc.
Disqualifiers: Pregnancy, Dementia, Systemic disease, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing OpRegen, a cell injection treatment, in patients with severe vision loss due to age-related macular degeneration. The goal is to see if injecting these cells under the retina can help repair or support damaged eye cells.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, if you have a systemic disease or are on treatments that could affect your health significantly, you might not be eligible to participate.
What data supports the effectiveness of the treatment OpRegen for age-related macular degeneration?
Research shows that human embryonic stem cell-derived retinal pigment epithelial (RPE) cells, like those in OpRegen, can improve visual function in animal models of retinal disease and have potential benefits for macular degeneration. These cells have been shown to rescue visual function and delay disease progression by replacing dysfunctional RPE cells, which are crucial for eye health.
12345Is OpRegen safe for humans?
Research shows that OpRegen, a treatment using retinal pigment epithelium (RPE) cells derived from human embryonic stem cells, has been tested in both animal models and early human trials. These studies indicate that the treatment is generally safe, with no significant adverse reactions or tumor formation observed in the tested subjects.
12678How is the OpRegen treatment different from other treatments for age-related macular degeneration?
OpRegen is unique because it involves transplanting retinal pigment epithelial (RPE) cells derived from human embryonic stem cells into the subretinal space, aiming to replace dysfunctional RPE cells and potentially restore vision in patients with age-related macular degeneration.
234910Eligibility Criteria
This trial is for individuals with geographic atrophy due to age-related macular degeneration who can undergo eye surgery under anesthesia. They should have a certain level of vision in the affected eye and must not be pregnant, breastfeeding, or have cognitive impairments or unstable systemic diseases.Inclusion Criteria
I have been diagnosed with geographic atrophy due to age-related macular degeneration.
BCVA score >/= 35 letters and </= 60 letters in the study eye as assessed by ETDRS
Pseudophakic (study eye)
+1 more
Exclusion Criteria
History of cognitive impairment or dementia
Any type of systemic disease or its treatment, in the opinion of the investigator, including any medical conditions that could bias the assessment of the clinical status of the patient or put the patient at special risk
Pregnancy or breastfeeding
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Subretinal surgical delivery of OpRegen cells to evaluate safety and activity
6 weeks
1 visit (in-person) for surgery, followed by weekly check-ups
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
Monthly visits (in-person)
Participant Groups
The study tests the effectiveness and safety of OpRegen when delivered through subretinal surgery in patients with geographic atrophy secondary to AMD. It aims to optimize surgical procedures and assess how well OpRegen works on the treated eye.
1Treatment groups
Experimental Treatment
Group I: OpRegenExperimental Treatment1 Intervention
OpRegen dose up to approximately 200,000 cells will be delivered into the subretinal space
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mid Atlantic RetinaCherry Hill, NJ
West Coast RetinaSan Francisco, CA
Mid Atlantic RetinaPhiladelphia, PA
Retinal Consultants Medical GroupSacramento, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Genentech, Inc.Lead Sponsor
References
Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. [2022]Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement tissue for human clinical studies. An early potential application of this technology is the use of retinal pigment epithelium (RPE) for the treatment of retinal degenerative diseases such as macular degeneration. Here we show the reproducible generation of RPE (67 passageable cultures established from 18 different hES cell lines); batches of RPE derived from NIH-approved hES cells (H9) were tested and shown capable of extensive photoreceptor rescue in an animal model of retinal disease, the Royal College of Surgeons (RCS) rat, in which photoreceptor loss is caused by a defect in the adjacent retinal pigment epithelium. Improvement in visual performance was 100% over untreated controls (spatial acuity was approximately 70% that of normal nondystrophic rats) without evidence of untoward pathology. The use of somatic cell nuclear transfer (SCNT) and/or the creation of banks of reduced complexity human leucocyte antigen (HLA) hES-RPE lines could minimize or eliminate the need for immunosuppressive drugs and/or immunomodulatory protocols.
Long-Term Efficacy of GMP Grade Xeno-Free hESC-Derived RPE Cells Following Transplantation. [2022]Retinal pigment epithelium (RPE) dysfunction underlies the retinal degenerative process in age-related macular degeneration (AMD), and thus RPE cell replacement provides an optimal treatment target. We characterized longitudinally the efficacy of RPE cells derived under xeno-free conditions from clinical and xeno-free grade human embryonic stem cells (OpRegen) following transplantation into the subretinal space of Royal College of Surgeons (RCS) rats.
Subretinal Transplantation of Human Central Nervous System Stem Cells Stimulates Controlled Proliferation of Endogenous Retinal Pigment Epithelium. [2022]The loss of retinal pigment epithelial (RPE) cells is a feature common to age-related macular degeneration (AMD) and retinitis pigmentosa (RP) and multiple early phase clinical trials are underway testing the safety of RPE cell replacement for these diseases. We examined whether transplantation of human neural stem cells into the subretinal space could enhance the endogenous proliferative capacity of the host RPE cell to regenerate.
Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration. [2022]Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area.
Immunological Properties of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells. [2019]Age-related macular degeneration is caused by dysfunction and loss of retinal pigment epithelium (RPE) cells, and their transplantation may rescue visual functions and delay disease progression. Human embryonic stem cells (hESCs) may be an unlimited source of RPE cells for allotransplantation. We analyzed the immunomodulatory properties of hESC-derived RPE (hESC-RPE) cells, and showed that they inhibited T cell responses. Co-culture experiments showed that RPE cells inhibited interfon-γ secretion and proliferation of activated T cells. Furthermore, hESC-RPE cells enhanced T cell apoptosis and secretion of the anti-inflammatory cytokine interleukin-10 (IL-10). In addition, RPE cells altered the expression of T cell activation markers, CD69 and CD25. RPE cells transplanted into RCS rats without immunosuppression survived, provided retinal rescue, and enhanced IL-10 blood levels. Our data suggest that hESC-RPE cells have immunosuppressive properties. Further studies will determine if these properties are sufficient to alleviate the need for immunosuppression therapy after their clinical allotransplantation.
Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. [2022]Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)-derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more. We report successful delivery and survival of the RPE patch by biomicroscopy and optical coherence tomography, and a visual acuity gain of 29 and 21 letters in the two patients, respectively, over 12 months. Only local immunosuppression was used long-term. We also present the preclinical surgical, cell safety and tumorigenicity studies leading to trial approval. This work supports the feasibility and safety of hESC-RPE patch transplantation as a regenerative strategy for AMD.
Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. [2022]Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness. Here we show long-term functional rescue using hESC-derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively. Good Manufacturing Practice-compliant hESC-RPE survived subretinal transplantation in RCS rats for prolonged periods (>220 days). The cells sustained visual function and photoreceptor integrity in a dose-dependent fashion without teratoma formation or untoward pathological reactions. Near-normal functional measurements were recorded at >60 days survival in RCS rats. To further address safety concerns, a Good Laboratory Practice-compliant study was carried out in the NIH III immune-deficient mouse model. Long-term data (spanning the life of the animals) showed no gross or microscopic evidence of teratoma/tumor formation after subretinal hESC-RPE transplantation. These results suggest that hESCs could serve as a potentially safe and inexhaustible source of RPE for the efficacious treatment of a range of retinal degenerative diseases.
A Preclinical Safety Study of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells for Macular Degeneration. [2021]Purpose: Age-related macular degeneration (AMD) is a common disease trending towards epidemic proportions and is a leading cause of irreversible vision loss in people over the age of 65. A pathomechanism of AMD is death and/or dysfunction of retinal pigment epithelial (RPE) cells; RPE loss invariably results in photoreceptor atrophy. Treatment options for AMD are very limited, and include vitamin supplements and lifestyle changes. An exciting potential therapy currently being tested in clinical trials is transplantation of stem cell-derived RPE. Methods: We developed a NIH-registered embryonic stem line (CR-4), and in this study set out to determine if CR4-RPE are tolerated in normal mice and in murine models of retinal degeneration by injecting a bolus of CR4-RPE cells in the subretinal space of immunosuppressed wild-type, Mer mutant (Merkd), and Elovl4 deficient mice. Results: Mice with CR-RPE grafts were monitored daily, were examined routinely using OCT, and histology was prepared and examined at terminal end-points. Based on the parameters of the study, none of the animals with CR-RPE grafts (n=36) experienced any obvious adverse reactions. Conclusions: We conclude that transplanted CR-4 hES-derived RPE cells are well tolerated in immunosuppressed healthy and dystrophic murine retinas.
The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue. [2023]Age-related macular degeneration (AMD) is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE) cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC)-derived RPE cells (RPESC-RPE) preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue. Whereas cells at all stages of differentiation tested rescued photoreceptor layer morphology, an intermediate stage of RPESC-RPE differentiation obtained after 4 weeks of culture was more consistent at vision rescue than progeny that were differentiated for 2 weeks or 8 weeks of culture. Our results indicate that the developmental stage of RPESC-RPE significantly influences the efficacy of RPE cell replacement, which affects the therapeutic application of these cells for AMD.
What's old is new again: Autologous stem cell transplant for AMD. [2018]Transplanted RPE cells derived from induced pluripotent stem cells maintained vision and were well tolerated in a patient with age-related macular degeneration.