Stem Cell Therapy for Age-Related Macular Degeneration

Recruiting at 10 trial locations

Overseen By Astellas Institute for Regenerative Medicine

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Astellas Institute for Regenerative Medicine

Must be taking: Tacrolimus

Must not be taking: Immunosuppressive therapy

Disqualifiers: Infections, Malignancy, Transplant history, others

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

Compensation: Varies

Number of Visits: 12

Duration: 1 day for injection, followed by up to 4 weeks of monitoring for each dose cohort

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new stem cell treatment called ASP7317 for individuals with age-related macular degeneration (AMD), a condition affecting central vision and complicating daily activities. The researchers aim to determine if injecting these cells under the retina can replace damaged cells and improve vision in those with geographic atrophy, an advanced form of dry AMD. Participants will be divided into groups based on their level of vision loss and will receive one of three different doses of ASP7317. Ideal candidates are older individuals with significant vision loss due to geographic atrophy related to dry AMD. Participants will also take medication, such as Tacrolimus, to prevent cell rejection and infection, and will attend regular follow-up visits for up to a year. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires participants to stop taking any medications that strongly interact with tacrolimus, a drug used in the study. If you are on such medications, you will need to discontinue them. However, if you are taking an antidepressant, you must continue it at a stable and effective dosage.

Is there any evidence suggesting that ASP7317 is likely to be safe for humans?

Research shows that ASP7317, a treatment derived from human stem cells, aims to assist individuals with age-related macular degeneration (AMD) by replacing damaged cells in the eye. Early studies have concentrated on the safety of injecting these stem cells into the eye. So far, these studies suggest that ASP7317 is generally well-tolerated by participants.

In earlier research, participants did not report any serious side effects directly related to the treatment. However, as with any new treatment, some mild to moderate side effects appeared, such as temporary eye inflammation or discomfort at the injection site. Standard treatments usually managed these effects.

Since this is a Phase 1 clinical trial, the primary goal is to ensure the treatment's safety for humans. The trial will closely monitor participants for any medical issues after receiving ASP7317 to gather more data on its safety. As the trial progresses, more information will become available to further confirm ASP7317's safety for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ASP7317 because it offers a novel approach to treating age-related macular degeneration (AMD) using stem cell therapy. Unlike current treatments that primarily focus on slowing the progression of vision loss or managing symptoms, ASP7317 involves implanting stem cells that have the potential to regenerate damaged retinal cells, addressing the root cause of vision deterioration. This innovative method could lead to longer-lasting vision improvement or even restoration, which is a significant advancement over existing therapies like anti-VEGF injections. By targeting the underlying cellular damage in AMD, ASP7317 provides hope for more effective and transformative outcomes.

What evidence suggests that ASP7317 might be an effective treatment for age-related macular degeneration?

Research has shown that treatments using stem cell-derived retinal pigment epithelium (RPE) cells, such as ASP7317, may aid in managing age-related macular degeneration (AMD). In this trial, participants will receive ASP7317 in different dose escalation groups based on their level of vision loss. Early studies of similar treatments have found that some patients experience improved vision or a halt in vision loss. These treatments replace damaged RPE cells in the eye, which are crucial for maintaining healthy vision. Initial results suggest that these new cells can integrate into the retina and might help restore some vision. While more research is needed, these early findings offer hope for people with dry AMD. ^{5 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

Adults over 50 with dry age-related macular degeneration (dry AMD) and geographic atrophy, resulting in central vision loss. Participants must be willing to discontinue certain supplements and medications, agree to use contraception if of childbearing potential, and not have a history of certain eye treatments or conditions that could affect the study's outcome.

Inclusion Criteria

Foveal sparing with potentially viable photoreceptors (EZ </= 250 microns from foveal center)

I agree not to breastfeed during the study and for a year after the last dose.

I will not donate eggs for one year after the study treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 8 weeks

Treatment

Participants receive ASP7317 injections under the macula with varying doses, along with tacrolimus and other medications to prevent infection

1 day for injection, followed by up to 4 weeks of monitoring for each dose cohort

Multiple visits for dose escalation and safety monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including eye tests and imaging

52 weeks

Several visits over 12 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• ASP7317
• Tacrolimus

Trial Overview The safety and effectiveness of ASP7317, a new cell-based therapy for dry AMD are being tested. Patients will receive one of three different doses via injection into the eye under anesthesia. They'll also take tacrolimus orally to prevent rejection of these cells. The trial includes frequent clinic visits for monitoring.

How Is the Trial Designed?

Group I: ASP7317 Dose Escalation/ Expansion (Group 2: Moderate Vision Loss) Experimental Treatment 5 Interventions

Successive cohorts of participants (3 participants each) will be given escalating doses (cohort 4: low cells/dose; cohort 5: medium cells/dose; cohort 6: high cells/dose). Optional Expansion cohorts 5b and 6b will be opened after cohorts 5 and 6 have been filled. Dose levels for the expansion cohorts will align with dose levels in escalation cohorts. Cohort 4 (low cells/dose) dosing may begin after the IDMC recommendation to begin dosing in Group 1 cohort 2 (medium cells/dose). Cohort 5 (medium cells/dose) dosing may begin after IDMC review of the 4- week safety data of the first participant in Group 1 cohort 2 (medium cells/dose). Cohort 6 (high cells/dose) dosing may begin after IDMC review of 4-week safety data of the first participant in Group 1 cohort 3 (high cells/dose). Dosing in cohort 5 and 6 can only begin after the IDMC review and the completion of the preceding cohort. Participants will receive tacrolimus and other medicines to stop infection.

Group II: ASP7317 Dose Escalation/ Expansion (Group 1: Severe Vision Loss) Experimental Treatment 5 Interventions

Successive cohorts of participants (3 participants each) will be given escalating doses (cohort 1: low cells/dose; cohort 2: medium cells/dose; cohort 3: high cells/dose). Optional Expansion cohorts 3b will be opened after cohort 3 has been filled and 2b will be opened only if necessary. Dose levels for the expansion cohort will align with dose levels in escalation cohorts. Sentinel dosing will be required for each dose level. After the first participant in each dose cohort in Group 1 is dosed and followed for 4 weeks, the Independent Data Monitoring Committee (IDMC) will review the 4-week safety data and recommend if the second and third participants in Group 1 dose cohort may be treated. The IDMC recommendation to progress to the next dosing cohort will be based on 4-week follow-up safety review of the second and third participants in the preceding dose cohort. Participants will receive tacrolimus and other medicines to stop infection.

Who Is Running the Clinical Trial?

Astellas Institute for Regenerative Medicine

Lead Sponsor

Trials

9

Recruited

150+

Published Research Related to This Trial

Human amniotic epithelial stem cells (hAESCs) can be effectively differentiated into retinal pigment epithelium (RPE)-like cells using trichostatin A and nicotinamide, showing similar characteristics to native RPE cells with low immunogenicity.

Transplanting these hAESCs-derived RPE-like cells into RCS rats improved their visual function and retinal structure, suggesting that this approach could be a promising therapy for age-related macular degeneration and other retinal degeneration diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Amniotic Epithelial Stem Cell-Derived Retinal Pigment Epithelium Cells Repair Retinal Degeneration. Li, J., Qiu, C., Wei, Y., et al.[2021]

The MA09-hRPE cell line, derived from human embryonic stem cells, has shown promise in treating macular degeneration, marking a significant step in addressing ethical and safety concerns associated with embryonic stem cell use.

This review highlights the importance of understanding host retinal factors that influence the efficacy of hESC-RPE transplants, suggesting that tailored clinical trials could enhance the development and commercialization of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of human embryonic stem cell-derived retinal pigment epithelial cells (MA09-hRPE) in macular degeneration. Qiu, TG.[2020]

Embedding human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells with polyelectrolytes using a layer-by-layer technique significantly reduced their immunogenicity while maintaining their functionality, which is crucial for successful transplantation.

Transplanting these engineered LbL-RPE cells into the subretinal space of RCS rats resulted in improved cell engraftment and enhanced visual function, as indicated by higher B wave amplitudes in electroretinogram recordings, demonstrating the potential of this method for treating retinal degenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving cell survival and engraftment in vivo via layer-by-layer nanocoating of hESC-derived RPE cells. Ru, L., Wu, N., Wei, K., et al.[2021]

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]

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]

A clinical trial involving three patients with wet age-related macular degeneration (wet-AMD) showed that transplanting human embryonic stem cell-derived retinal pigment epithelial cells (Q-CTS-hESC-2-RPE) was safe, with no adverse effects observed over 12 months.

Anatomical improvements were noted, including the formation of a new RPE-like cell layer in damaged areas, suggesting potential for retinal repair, although functional vision improvements were limited and varied among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human embryonic stem cell-derived retinal pigment epithelium transplants as a potential treatment for wet age-related macular degeneration. Liu, Y., Xu, HW., Wang, L., et al.[2020]

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]

Two phase I/II studies involving 18 patients with advanced macular degeneration showed that implanting human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) is safe and may improve visual acuity in over half of the treated patients.

No significant adverse events related to the cell therapy were observed, aside from one case of postoperative infection, suggesting a favorable safety profile for future studies and potential treatments for other retinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years. Schwartz, SD., Tan, G., Hosseini, H., et al.[2022]

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, with no current treatment for advanced non-neovascular AMD (NNV-AMD), highlighting the urgent need for effective therapies.

Research into using human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) and induced pluripotent stem cell-derived RPE (iPSC-RPE) shows promise in restoring vision by replacing damaged RPE cells, but significant ethical and safety challenges remain before these therapies can be widely implemented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell based therapies for age-related macular degeneration: The promises and the challenges. Nazari, H., Zhang, L., Zhu, D., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01345006

Sub-retinal Transplantation of hESC Derived RPE(MA09- ... This is a safety and tolerability trial to evaluate the effect of subretinal injection of human embryonic stem cell derived retinal pigment epithelium cells in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10097914/

Stem cell-derived retinal pigment epithelium cell therapy First reports of trials using hESC-derived RPE cells and a similar approach (Kashani et al., 2020) indicate positive outcomes with respect to ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0039625724000493

Gene and cell therapy for age-related macular degeneration The AREDS trials studied the effect of nutritional supplementation on AMD progression and found it to be effective in slowing disease progression rate 33, 47, ...

4. 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), ...

5. reviewofophthalmology.com reviewofophthalmology.com/article/cell-therapy-clinical-trials-an-update

Cell Therapy Clinical Trials: An Update Unlike the initial dose-escalating study, this trial is focusing only on safety and efficacy results of the 200,000 hESC-RPE cell dosage, with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01344993

Study Details | NCT01344993 | Safety and Tolerability of ... This is a safety and tolerability trial to evaluate the effect of subretinal injection of human embryonic stem cell derived retinal pigment epithelium cells

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6712006/

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

8. go.drugbank.com go.drugbank.com/drugs/DB18549

ASP-7317: Uses, Interactions, Mechanism of Action ASP-7317 consists of human embryonic stem cell-derived retinal pigment epithelium cells. Modality: Cell transplant therapies. Other cell ...

9. clinicaltrials.astellas.com clinicaltrials.astellas.com/study/7317-CL-0003

A study of the safety and tolerability of ASP7317 in senior ... A study of the safety and tolerability of ASP7317 in senior adults who are losing their clear, sharp central vision due to geographic atrophy secondary to dry ...