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 (MA09-hRPE) 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
- 13
- 试验地点
- 3
- 主要终点
- Safety Assessments
研究概览
简要总结
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 patients with Stargardt's Macular Dystrophy (SMD).
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 Vison 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
- Other
- 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 advanced 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.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.
- •Peripheral visual field constriction documented on standard kinetic visual field testing.
- •Electrophysiological findings consistent with SMD.
- •Medically suitable to undergo vitrectomy and subretinal injection.
- •Medically suitable for general anesthesia 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), 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 & if over age 50 years, negative colonoscopy within previous 7 years;
- •negative chest roentgenogram (CXR);
- •normal CBC & manual differential;
- •negative urinalysis (U/A);
- •normal thyroid exam;
- •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 40 years of age or older, negative mammogram.
- •If female and of childbearing potential, willing to use two effective forms 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.
- •If female, pregnancy or lactation.
- •Any other medical condition, which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromises patient safety, or interferes with the interpretation of the study results.
研究组 & 干预措施
MA09-hRPE
Patients will undergo subretinal injection of MA09-hRPE
干预措施: MA09-hRPE (Biological)
结局指标
主要结局
Safety Assessments
时间窗: 12 months
* Adverse Event and Serious Adverse Event assessment * Clinical monitoring * Serial vital signs * Clinical laboratory tests * Directed ophthalmological monitoring * Monitoring of RPE cells acceptance/integrity/rejection * Monitoring of local and systemic infection * Monitoring of tumorigenic cell transformation
The safety and tolerance of transplantation of hESC-derived RPE cells MA09-hRPE
时间窗: 12 months
The transplantation of hESC-derived RPE cells 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 * Any evidence that the cells show tumorigenic potential
次要结局
- Evidence of successful engraftment(12 months)