Study in Human iPSCs-derived RPE Cells Transplantation for Late-Stage AMD

Official title

Study in Human iPSCs-derived Retinal Pigment Epithelium Cells Transplantation for Late-Stage Age-Related Macular Degeneration

Overview

Phase I Study of the Safety and Preliminary Efficacy of Human induced pluripotent stem cells-derived Retinal Pigment Epithelial (HiPSC-RPE) Cells Subretinal Transplantation in Late-Stage Age-Related Macular Degeneration(AMD) Patients

Interventions

• Biological HiPSC-RPE cells
  HiPSC-RPE cells transplantation directly into the subretinal space of one eye (experimental eye) in a single transplant procedure
• Drug Erlotinib (150 mg daily)
  Subjects began oral administration of erlotinib one day before surgery at a dose of 150 mg once daily for a total duration of 1 month.
• Drug Prednisone
  Prednisone was initiated 3 days prior to surgery at a dose of 30 mg/day (5 mg per tablet, 6 tablets daily) and continued for 6 weeks, with the dose tapered by one tablet per week until discontinuation.

Primary outcome measures

• Number of subjects with adverse events [Time frame: Two years following transplantation]

Secondary outcome measures (2)

• Assessment of visual acuity using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. [Time frame: From enrollment to the end of visiting at 2 years]
• Assessment of visual function changes-microperimetry [Time frame: From enrollment to the end of visiting at 2 years]

Eligibility criteria

Inclusion criteria

• (1)Age ≥50 years and ≤80 years, regardless of gender.
• (2)Patients with atrophic AMD in the macular area (geographic atrophy >250μm, involving the foveal center); or stable non-exudative AMD patients who have undergone treatment for wet AMD or have naturally converted to non-exudative AMD (referring to patients with fibrovascular scar formation, who are unresponsive to anti-VEGF treatment, and have no macular edema on OCT and/or no fluorescein leakage on FFA), with a scar diameter not exceeding 6 PD.
• (3)Best-corrected visual acuity (BCVA) of the study eye ≥5 letters and ≤34 letters (using the ETDRS visual acuity chart).
• (4)If both eyes meet the criteria, the more severely affected eye will be selected; if the severity is the same in both eyes, the right eye will be designated as the study eye.
• (5)The patient or their legal representative has signed a written informed consent form.

Exclusion criteria

• Ocular Diseases:
• (1)Vitreous hemorrhage in the study eye within 2 months prior to screening.
• (2)Presence of a scar, fibrosis, or atrophy involving the fovea in the study eye, or a peripheral scar area greater than 6 PD, indicating severe irreversible visual loss.
• (3)Presence of pseudoexfoliation syndrome, central retinal vein occlusion, intraocular hemorrhage causing visual loss, rhegmatogenous retinal detachment, macular hole, or choroidal neovascularization due to any cause in the study eye.
• (4)Presence of a pupillary block defect (APD) in the study eye.
• (5)Significant media opacity in the study eye that may interfere with visual function assessment or fundus examination.
• (6)Acute infectious inflammation in either eye during the screening period.
• (7)Patients with intraocular pressure higher than 25 mmHg despite medical treatment.
• (8)Monocular blind patients.

Ocular Treatments:

• (9)The study eye has undergone focal/grid laser photocoagulation within 3 months prior to screening.
• (10)The study eye has undergone the following intraocular surgeries or laser treatments within 3 months prior to screening, such as macular translocation, cataract surgery, glaucoma filtration surgery, verteporfin photodynamic therapy, transpupillary thermotherapy, foveal laser photocoagulation, vitrectomy, optic nerve decompression, or optic nerve sheath decompression.
• (11)Any eye has received anti-angiogenic drug treatment (including any anti-VEGF drugs) within 3 months prior to screening (e.g., Aflibercept \[Eylea®\], Ranibizumab \[Lucentis®\], Bevacizumab \[Avastin®\]).

Systemic Diseases, Treatments, and Other Conditions:

• (12)Patients with an allergic reaction or history of allergy to sodium fluorescein and indocyanine green, a history of allergy to protein products used for treatment or diagnosis, and patients with allergies to two or more drugs and/or non-drug factors, or those currently suffering from allergic diseases.
• (13)Patients with uncontrolled diabetes (fasting blood glucose ≥7.0 mmol/L or 2-hour postprandial blood glucose ≥11.1 mmol/L).
• (14)Patients with a history of surgical procedures within 1 month prior to screening, or those with unhealed wounds, ulcers, fractures, etc.
• (15)Patients with uncontrolled hypertension (defined as a single measurement of systolic blood pressure >180 mmHg, two consecutive measurements of systolic blood pressure >160 mmHg, or diastolic blood pressure >100 mmHg despite optimal treatment).
• (16)Patients with a history of myocardial infarction within 6 months prior to enrollment.
• (17)Patients with active disseminated intravascular coagulation or a significant tendency to bleed; patients who have used anticoagulant or antiplatelet aggregation drugs within 14 days prior to screening, except for aspirin/nonsteroidal anti-inflammatory drugs.
• (18)Patients with any uncontrollable clinical issues (such as severe psychiatric, neurological, cardiovascular, respiratory, malignant tumors, Parkinson's disease, Alzheimer's disease, and other systemic diseases).
• (19)Women of childbearing age with a positive pregnancy test during the screening period. Women who wish to breastfeed during the study period, and all patients of childbearing age (male and female) who do not agree to take effective contraceptive measures (such as intrauterine devices, oral contraceptives, or condoms) throughout the study period and for 30 days after the end of the visit period.
• (20)Patients who have participated in or are currently participating in other clinical studies within 30 days prior to screening.
• (21)Hemoglobin <100 g/L, platelets ≤100×109/L, neutrophil count <1.0×109/L, ALT/AST >1.5×upper limit of normal (ULN), creatinine >1.3 mg/dL.
• (22)Patients deemed unsuitable for inclusion by the investigator, or other medical conditions that limit the subject's compliance, safety, or affect the results of the study trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital with Nanjing Medical University — Nanjing

Identifiers

NCT: NCT07418177 · JSPH-iPSCs-RPE-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗