OpRegen for Age-Related Macular Degeneration

Recruiting at 9 trial 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. ^{1 2 3 4 5}

Is 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. ^{1 2 6 7 8}

How 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. ^{2 3 4 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility 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)

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)

Treatment Details

Interventions

• OpRegen (Stem Cell Therapy)

Trial Overview 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.

Participant Groups

Group I: OpRegen Experimental Treatment 1 Intervention

OpRegen dose up to approximately 200,000 cells will be delivered into the subretinal space

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

Researchers successfully generated retinal pigment epithelium (RPE) from 18 different human embryonic stem cell lines, demonstrating a reproducible method for creating replacement tissue for retinal diseases.

In an animal model of retinal degeneration, RPE derived from these stem cells improved visual performance by 100% compared to untreated controls, showing significant potential for treating conditions like macular degeneration without causing harmful side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Lund, RD., Wang, S., Klimanskaya, I., et al.[2022]

Transplantation of xeno-free RPE cells derived from human embryonic stem cells (OpRegen) into RCS rats showed a dose-dependent improvement in visual function and preservation of photoreceptors over a long-term period, indicating their potential efficacy for treating retinal diseases like age-related macular degeneration (AMD).

The study demonstrated that these transplanted RPE cells not only survived and integrated into the host tissue but also did not cause any adverse effects, highlighting their safety and suitability for future clinical applications in human retinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy of GMP Grade Xeno-Free hESC-Derived RPE Cells Following Transplantation. McGill, TJ., Bohana-Kashtan, O., Stoddard, JW., et al.[2022]

Transplanting human neural stem cells (HuCNS-SC) into the subretinal space significantly increased the proliferation of host retinal pigment epithelial (RPE) cells in dystrophic rat models, showing about a threefold increase in cell proliferation compared to controls.

This study suggests that enhancing the natural regenerative capacity of RPE cells through HuCNS-SC transplantation could be a promising new approach for treating age-related macular degeneration and retinitis pigmentosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subretinal Transplantation of Human Central Nervous System Stem Cells Stimulates Controlled Proliferation of Endogenous Retinal Pigment Epithelium. McGill, TJ., Osborne, L., Lu, B., et al.[2022]

In a Phase 1/2 trial involving 12 participants with advanced Stargardt disease, transplantation of hESC-derived retinal pigment epithelial (RPE) cells showed safety with no uncontrolled proliferation or inflammatory responses, but only borderline improvements in visual acuity were observed, which were not sustained.

The study found subretinal hyperpigmentation in all participants, indicating potential survival of transplanted cells, but also suggested that this could reflect released pigment rather than effective treatment, highlighting the need for caution in early-stage interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration. Mehat, MS., Sundaram, V., Ripamonti, C., et al.[2022]

The engineered RPE patch, derived from human embryonic stem cells, was successfully implanted in two patients with severe age-related macular degeneration (AMD), showing promising results in visual acuity improvement of 29 and 21 letters over 12 months.

The procedure demonstrated safety with only local immunosuppression required long-term, supporting the potential of hESC-RPE patch transplantation as a regenerative treatment for AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. da Cruz, L., Fynes, K., Georgiadis, O., et al.[2022]

Human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) showed long-term functional rescue in animal models of retinal degeneration, sustaining visual function for over 220 days without causing teratoma formation.

In a Good Laboratory Practice-compliant study, hESC-RPE transplantation in immune-deficient mice demonstrated no evidence of tumor formation, indicating a promising safety profile for potential clinical applications in treating retinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Lu, B., Malcuit, C., Wang, S., et al.[2022]

Transplanted stem cell-derived retinal pigment epithelial (RPE) cells from the CR-4 embryonic stem line were well tolerated in a study involving 36 immunosuppressed mice, showing no obvious adverse reactions.

This research suggests that CR-4 RPE cell transplantation could be a promising therapeutic approach for age-related macular degeneration (AMD), a leading cause of vision loss, as it demonstrates safety in murine models of retinal degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Preclinical Safety Study of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells for Macular Degeneration. Mazzilli, JL., Snook, JD., Simmons, K., et al.[2021]

Transplanting retinal pigment epithelial (RPE) cells derived from RPE stem cells (RPESC-RPE) into the eyes of rats with RPE dysfunction successfully preserved vision, indicating a potential treatment for age-related macular degeneration (AMD).

The effectiveness of vision rescue was significantly influenced by the differentiation stage of the RPESC-RPE cells prior to transplantation, with cells cultured for 4 weeks showing the best results compared to those cultured for 2 or 8 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue. Davis, RJ., Alam, NM., Zhao, C., et al.[2023]

Transplanted retinal pigment epithelium (RPE) cells derived from induced pluripotent stem cells successfully maintained vision in a patient with age-related macular degeneration, indicating potential for this treatment in restoring sight.

The RPE cell transplant was well tolerated by the patient, suggesting a favorable safety profile for this innovative approach in treating retinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What's old is new again: Autologous stem cell transplant for AMD. Byrne, LC.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy of GMP Grade Xeno-Free hESC-Derived RPE Cells Following Transplantation. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Subretinal Transplantation of Human Central Nervous System Stem Cells Stimulates Controlled Proliferation of Endogenous Retinal Pigment Epithelium. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Immunological Properties of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

A Preclinical Safety Study of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells for Macular Degeneration. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

What's old is new again: Autologous stem cell transplant for AMD. [2018]