42 Participants Needed

Stem Cell Therapy for Age-Related Macular Degeneration

Recruiting at 10 trial locations
AI
Overseen ByAstellas Institute for Regenerative Medicine
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Astellas Institute for Regenerative Medicine
Must be taking: Tacrolimus
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

Age-related macular degeneration (AMD) is an eye disease which causes people to lose their sharp central vision over time. Aging damages the macula, which is in the middle of the retina - the light-sensitive part at the back of the eye. There are 2 types of AMD - wet AMD and dry AMD. The advanced stage of dry AMD causes vision loss. This is known as geographic atrophy. AMD makes everyday tasks like reading or driving difficult. ASP7317 is a potential new treatment for people with AMD. ASP7317 are human stem cells which have changed into cells found in the retina. ASP7317 is injected under the macula. It is hoped that ASP7317 will replace some of the damaged cells in the macula and improve vision for people with dry AMD. Before ASP7317 is available as a treatment, the researchers need to check its safety and how well it is tolerated. They will also check for signs of improved vision. People taking part in this study will be older people who have geographic atrophy caused by dry AMD. This is an open-label study. This means that people in this study and clinic staff will know that people will receive ASP7317. There will be 3 doses of ASP7317. These are low, medium and high numbers of cells. ASP7317 will be injected under the macula after the person is given either a local or a general anesthetic. To prevent the body from rejecting the cells, people will take tablets of tacrolimus a few days before receiving ASP7317 for up to a few weeks afterwards. Other medicines will be taken during this time to stop infections. There will be 2 groups in the study. Group 1 will be people with severe vision loss and Group 2 will be people with moderate vision loss. There will be different small groups of people within Group 1 and Group 2, with each small group receiving 1 of the 3 doses of ASP7317. Different small groups of people within Group 1 and Group 2 will receive lower to higher doses of ASP7317. Each small group will only receive 1 dose. Group 1 will start treatment first. At each dose, a medical expert panel will check the results of the first person in the group to decide if the rest of the group will receive the same dose. Then, the panel will decide if more people may receive the same dose or if the next group may receive the next highest dose. The panel will use the results from the lower dose of Group 1 to decide when Group 2 starts treatment (also at the lower dose). The panel will also use the results of the middle and higher doses in Group 1 to decide when and how many people in Group 2 can receive these doses. During the study, people will visit the clinic several times for up to 12 months (1 year). During all visits, the study doctors will check for any medical problems after receiving ASP7317. Vital signs will be checked a few days before treatment with ASP7317 and up to about a month afterwards. Vital signs include blood pressure, pulse, and temperature. At some visits, the study doctors will also take blood samples for blood tests. At most visits, people will have eye tests and have different images, scans, and measurements taken. This could be for the affected eye or both eyes, depending on the test. People can visit the clinic extra times, if needed.

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.

What data supports the effectiveness of the treatment for age-related macular degeneration?

Research shows that transplanting human embryonic stem cell-derived retinal pigment epithelial cells can improve vision in patients with macular degeneration by replacing damaged cells in the eye. Studies have demonstrated that these cells can integrate into the retina and lead to functional improvements, although challenges remain in optimizing their use.12345

Is stem cell therapy for age-related macular degeneration safe?

Research shows that stem cell therapy using human embryonic stem cell-derived retinal pigment epithelial cells has been generally safe in early trials for age-related macular degeneration. No major safety issues like tumor growth or severe inflammation were reported, although one case of infection occurred after surgery.23467

How is the treatment ASP7317 unique for age-related macular degeneration?

ASP7317 is unique because it uses human embryonic stem cell-derived retinal pigment epithelial cells to replace damaged cells in the eye, potentially improving vision in patients with age-related macular degeneration. This approach is novel as it aims to restore the function of the retina by directly transplanting healthy cells, unlike other treatments that mainly focus on slowing disease progression.23489

Research Team

MD

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Eligibility Criteria

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.
See 74 more

Timeline

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

Treatment Details

Interventions

  • ASP7317
  • Tacrolimus
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: ASP7317 Dose Escalation/ Expansion (Group 2: Moderate Vision Loss)Experimental Treatment5 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 Treatment5 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.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Astellas Institute for Regenerative Medicine

Lead Sponsor

Trials
9
Recruited
150+

Findings from Research

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.
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]
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.
Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.Mehat, MS., Sundaram, V., Ripamonti, C., et al.[2022]
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.
Transplantation of human embryonic stem cell-derived retinal pigment epithelial cells (MA09-hRPE) in macular degeneration.Qiu, TG.[2020]

References

Improving cell survival and engraftment in vivo via layer-by-layer nanocoating of hESC-derived RPE cells. [2021]
Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration. [2022]
Transplantation of human embryonic stem cell-derived retinal pigment epithelial cells (MA09-hRPE) in macular degeneration. [2020]
Stem cell based therapies for age-related macular degeneration: The promises and the challenges. [2022]
A Preclinical Safety Study of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells for Macular Degeneration. [2021]
Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. [2022]
Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years. [2022]
Human Amniotic Epithelial Stem Cell-Derived Retinal Pigment Epithelium Cells Repair Retinal Degeneration. [2021]
Human embryonic stem cell-derived retinal pigment epithelium transplants as a potential treatment for wet age-related macular degeneration. [2020]