OpRegen for Age-Related Macular Degeneration

Not currently recruiting at 12 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Lineage Cell Therapeutics, Inc.

Must not be taking: Aspirin, Coagulation modifying drugs

Disqualifiers: Neovascular AMD, Diabetic retinopathy, Uncontrolled glaucoma, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called OpRegen, a retinal pigment epithelium transplant therapy, to determine its safety and ability to slow the progression of dry age-related macular degeneration (AMD), a condition affecting vision. Researchers aim to discover if the transplanted cells can survive and enhance eye health. Ideal participants are aged 50 or older, diagnosed with dry AMD in both eyes, and experiencing vision difficulties, such as legally blind vision levels, in at least one eye. As a Phase 1, Phase 2 trial, participants will be among the first to receive this treatment and assist researchers in measuring its effectiveness in improving eye health.

Will I have to stop taking my current medications?

The trial requires that you stop taking aspirin, aspirin-containing products, and any other blood-thinning medications at least 7 days before surgery. For other medications, the protocol does not specify, so it's best to discuss with the study team.

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

Research shows that OpRegen, a stem cell treatment, is being tested for safety in people with age-related macular degeneration (AMD). In earlier studies, most patients tolerated the treatment well. One study found no serious side effects directly caused by the treatment. Some patients experienced mild side effects, but these were not serious.

This treatment works by placing new retinal cells into the eye to help slow down AMD. Early results suggest that OpRegen could be a promising option, as it has shown potential benefits with manageable side effects. Since this trial is in the early stages, it focuses primarily on ensuring the treatment's safety before assessing its potential to improve vision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

OpRegen is unique because it involves a novel approach to treating age-related macular degeneration (AMD) by using retinal pigment epithelial cells derived from human embryonic stem cells. Unlike standard treatments like anti-VEGF injections, which primarily focus on slowing vision loss, OpRegen aims to replace damaged cells and potentially restore vision. This regenerative strategy targets the underlying cause of the disease, offering hope for more lasting and meaningful improvements in vision. Researchers are excited about OpRegen because it represents a shift towards regenerative medicine, potentially offering a groundbreaking solution for those with significant vision impairment.

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

Research has shown that OpRegen, a treatment using specialized cells from human embryonic stem cells, may aid in age-related macular degeneration (AMD). In earlier studies, these cells survived in the eye and improved vision for some individuals with dry AMD. OpRegen has demonstrated the ability to maintain vision and protect the eye cells that detect light, potentially slowing vision loss in AMD. While early results are promising, ongoing studies, including this trial, continue to evaluate the treatment's effectiveness. ^{1 2 3 5 6}

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 aged 50 or older with advanced dry-form age-related macular degeneration (AMD) in both eyes. Participants must have a central visual acuity of 20/200 or worse, be in good health to undergo surgery and follow-up procedures, and not have any significant eye diseases other than AMD. They cannot have active infections like TB, HIV, hepatitis B/C, CMV IgM, EBV IgM or a history of certain cancers unless in remission for over five years.

Inclusion Criteria

I have been diagnosed with dry age-related macular degeneration in both eyes.

Best corrected central visual acuity equal or less than 20/200 in cohorts 1-3 and 20/64-20/250 in cohort 4 in the study eye by ETDRS vision testing

Vision in the non-operated eye must be better than or equal to that in the operated eye

Exclusion Criteria

Any type of systemic disease or its treatment, in the opinion of the Investigator, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk

Current participation in another clinical study. Past participation (within 6 months) in any clinical study of a drug administered systemically or to the eye

I have been diagnosed with wet AMD in at least one eye.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive OpRegen transplantation to evaluate safety and tolerability

12 months

Multiple visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits

Long-term follow-up

Participants are monitored for long-term safety and adverse events

Up to 6.5 years

What Are the Treatments Tested in This Trial?

Interventions

• OpRegen

Trial Overview The study tests the safety and effectiveness of OpRegen - cells derived from human embryonic stem cells intended to replace damaged retinal pigment epithelial (RPE) cells. It aims to see if these transplanted cells can integrate into the retina, survive long-term and slow down disease progression in patients with AMD.

How Is the Trial Designed?

Group I: OpRegen Experimental Treatment 1 Intervention

Up to 12 legally blind subjects with best corrected visual acuity of 20/200 or less in first three cohorts and 12 subjects with best corrected visual acuity of 20/64 and 20/250 in fourth cohort

Who Is Running the Clinical Trial?

Lineage Cell Therapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

90+

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

CellCure Neurosciences Ltd.

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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. 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- ...

3. 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5472365/

Long-Term Efficacy of GMP Grade Xeno-Free hESC-Derived ... OpRegen RPE cells survived, rescued visual function, preserved rod and cone photoreceptors long-term in the RCS rat. Thus, these data support ...

5. aao.org aao.org/eyenet/article/rpe-cell-transplants-for-dry-amd

RPE Cell Transplants for Dry AMD In a phase 1/2A clinical trial, cultured retinal pigment epithelial (RPE) cells were successfully transplanted into patients with advanced dry age-related ...

6. nature.com nature.com/articles/s41536-019-0081-8

Transplantation of human embryonic stem cell-derived ... This review focuses on the first generation of hESC-RPE cell line, named as “MA09-hRPE” by Astellas Institute of Regenerative Medicine (AIRM), ...