OpRegen for Age-Related Macular Degeneration

Recruiting at 17 trial locations

Overseen By Reference Study ID Number: GR44251 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genentech, Inc.

Disqualifiers: Pregnancy, Dementia, Systemic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a new treatment called OpRegen, a retinal pigment epithelium transplant therapy, for individuals with geographic atrophy. This condition, linked to age-related macular degeneration, damages the retina. The trial aims to determine if OpRegen can slow down or improve this eye condition. Suitable participants have geographic atrophy due to age-related macular degeneration and can undergo a specific eye surgery. A substudy uses a special imaging device to capture detailed eye pictures for research purposes only, without affecting patient care. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that OpRegen is likely to be safe for humans?

Research has shown that OpRegen, a treatment for age-related macular degeneration, is generally well-tolerated. In earlier studies, patients received OpRegen without experiencing serious side effects. These studies focused on the safety of placing cells into the eye, and the treatment proved safe for patients with advanced stages of the disease.

The treatment involves placing cells into a specific part of the eye to help improve vision. Reports from these studies indicated that the procedure was safe and did not cause major problems for patients. This is a promising sign for the safety of OpRegen in treating geographic atrophy related to age-related macular degeneration. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AMD?

OpRegen is unique because it delivers a dose of up to approximately 200,000 retinal pigment epithelial cells directly into the subretinal space. This is different from standard treatments for age-related macular degeneration, like anti-VEGF injections, which focus on slowing vision loss by targeting blood vessel growth. OpRegen's approach aims to replace damaged cells in the eye, potentially restoring vision rather than just preserving it. Researchers are excited about OpRegen because it represents a promising regenerative therapy, which could offer a more long-term solution to vision impairment associated with this condition.

What evidence suggests that OpRegen might be an effective treatment for age-related macular degeneration?

Research has shown that OpRegen, a cell therapy, offers promising results for treating geographic atrophy (GA) associated with age-related macular degeneration (AMD). In one study, patients who received OpRegen experienced improved vision clarity over 12, 24, and 36 months. This suggests the treatment might help regain some vision lost due to GA. The therapy involves transplanting healthy cells into the eye, which are crucial for eye health and may prevent further damage. Overall, evidence supports OpRegen's potential to improve vision in GA patients. ^{1 6 7 8 9}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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

BCVA score >/= 35 letters and </= 60 letters in the study eye as assessed by ETDRS

I have been diagnosed with geographic atrophy due to age-related macular degeneration.

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• OpRegen

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

Human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) cells have shown the ability to inhibit T cell responses, suggesting they possess immunomodulatory properties that could be beneficial for transplantation.

In experiments with RCS rats, hESC-RPE cells survived without the need for immunosuppression, provided retinal rescue, and increased levels of the anti-inflammatory cytokine IL-10, indicating their potential for safe allotransplantation in treating age-related macular degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological Properties of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells. Idelson, M., Alper, R., Obolensky, A., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02286089

NCT02286089 | Safety and Efficacy Study of OpRegen for ... This is a Phase I/IIa, dose-escalation, evaluating safety and tolerability of OpRegen transplantation to patients with progressive dry-AMD.

2. ophthalmologytimes.com ophthalmologytimes.com/view/36-month-results-from-phase-1-2a-clinical-study-of-rg6501-released

36-month results from phase 1/2a clinical study of RG6501 ... New findings reveal RG6501 cell therapy shows promising long-term visual improvements for geographic atrophy patients.

3. firstwordpharma.com firstwordpharma.com/story/5975367

OpRegen (RG6501) 36-Month Visual Acuity Results ... OpRegen-treated eyes have exhibited mean BCVA scores above baseline at each of the 12-, 24-, and 36-month timepoints, demonstrating consistency as well as ...

4. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2780049

Safety and Efficacy of a Phase 1/2a Clinical Trial of ... - IOVS Purpose : Transplanted healthy RPE cells may benefit AMD patients. We created allogenic RPE cells (OpRegen) using directed differentiation.

5. en.wikipedia.org en.wikipedia.org/wiki/OpRegen

OpRegen OpRegen (also known as RG6501) is an investigational allogeneic cell therapy developed by Lineage Cell Therapeutics for the treatment of geographic atrophy ...

6. cell.com cell.com/cell-stem-cell/fulltext/S1934-5909(25)00304-2

Safety and tolerability of RPESC-RPE transplantation in ... Stem cell-based cell replacement therapies are under development to implant RPE cells into areas of RPE atrophy to improve vision for dry AMD ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12384370/

Retinal Pigment Epithelium Transplantation in Retinal Disease Replacement of the retinal pigment epithelium (RPE) is emerging as a promising approach to treat degenerative retinal diseases, including age- ...

8. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2745401

Phase I/IIa Clinical Trial of Human Embryonic Stem Cell ... Conclusions : Subretinal transplantation of hESC-derived RPE cells in patients with advanced dry AMD and GA appears well tolerated to date. Imaging findings ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11526680/

Advances in retinal pigment epithelial cell transplantation for ... This review provides a comprehensive overview of the recent advancements in clinical trials related to RPE transplantation.