A Phase I/II, Open-Label, Multi-Center, Prospective Study to Determine the Safety and Tolerability of Sub-retinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigmented Epithelial (hESC-RPE) Cells in Patients With Stargardt's Macular Dystrophy (SMD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 3
- 主要终点
- safety and tolerance of transplantation
研究概览
简要总结
The purpose of this study is:
To evaluate the safety and tolerability of RPE cellular therapy in patients with SMD .
To evaluate potential efficacy endpoints to be used in future studies RPE cellular therapy.
详细描述
This study is a Phase I/II, open-label, non randomized, sequential, multi-center clinical trial. There will be 5 cohorts, the 4 low vision cohorts will contain 3 patients, the better vision cohort will contain 4 patients. The enrolled cohorts will be as follows:
Three SMD patients- 50,000 MA09-hRPE cells transplanted
Three SMD patients- 100,000 MA09-hRPE cells transplanted
Four Better Vision SMD patients- 100,000 MA09-hRPE cells transplanted
Three SMD patients- 150,000 MA09-hRPE cells transplanted
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult male or female over 18 years of age. Clinical diagnosis of SMD If known, the patient"s genotype will be recorded in the medical history, if unknown, patient will allow for the submission of a sample for genotyping.
- •Independently verified clinical findings consistent with SMD. The visual acuity of the eye to receive the transplant will be no better than 20/
- •The visual acuity of the eye in the better vision cohort to receive the transplant will be no better than 20/
- •The visual acuity of the eye that is not to receive the transplant will be no better than 20/400 for the worse vision patients and no worse than 20/100 for the better vision patients.
- •Electrophysiological findings consistent with SMD . Medically suitable to undergo vitrectomy and subretinal injection. Medically suitable for general anaesthesia or waking sedation, if needed.
- •Medically suitable for transplantation of an embryonic stem cell line:
- •Normal serum chemistry (sequential multi-channel analyzer 20 [SMA-20]) and hematology (complete blood count [CBC], prothrombin time [PT], and activated partial thromboplastin time [aPTT]) screening tests.
- •Negative urine screen for drugs of abuse.
- •Negative human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV) serologies.
- •No history of malignancy, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin.
- •Negative cancer screening within previous 6 months:
- •complete history & physical examination; dermatological screening exam for malignant lesions; negative fecal occult blood test negative chest roentgenogram (CXR); normal CBC & manual differential; negative urinalysis (U/A);normal thyroid exam and thyroid panel; if male, normal testicular examination; if over age 40, digital rectal examination (DRE) and prostate specific antigen (PSA); if female, normal pelvic examination with Papanicolaou smear; and if female, normal clinical breast exam and if 50 years of age or older, negative mammogram.
- •If female and of childbearing potential, willing to use an effective form of birth control during the study.
- •If male, willing to use barrier and spermicide contraception during the study. Willing to defer all future blood, blood component or tissue donation. Able to understand and willing to sign the informed consent.
排除标准
- •History of malignancy, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin.
- •History of myocardial infarction in previous 12 months. History of diabetes mellitus. Any immunodeficiency. Any current immunosuppressive therapy other than intermittent or low dose corticosteroids.
- •Serologic evidence of infection with Hepatitis B, Hepatitis C, or HIV. Current participation in any other clinical trial. Participation within previous 6 months in any clinical trial of a drug by ocular or systemic administration.
- •Any other sight-threatening ocular disease. Any chronic ocular medications. Any history of retinal vascular disease (compromised blood-retinal barrier. Glaucoma. Uveitis or other intraocular inflammatory disease. Significant lens opacities or other media opacity. Ocular lens removal within previous 3 months
研究组 & 干预措施
Subretinal injection of MA09-hRPE
- Cohort 1 50,000 cells
- Cohort 2 100,000 cells
- Cohort 2a Better Vision 100,000 cells
- Cohort 3 150,000 cells
- Cohort 4 200,000 cells
干预措施: MA09-hRPE (Biological)
结局指标
主要结局
safety and tolerance of transplantation
时间窗: 12 months
The safety and tolerance of transplantation of hESC-derived MA09-hRPE will be considered safe and tolerated in the absence of: Any grade 2 NCI grading system)or greater adverse event related to the cell product.Any evidence that the cells are contaminated with an infectious agent, or have tumorigenic potential, Adverse Event and Serious Adverse Event assessment, Serial vital signs and Clinical laboratory tests Direct ophthalmological monitoring Monitoring of RPE cells acceptance/integrity/rejection Monitoring of local and systemic infection or tumorigenic cell transformation
次要结局
- Evidence of successful engraftment(12 months)