Safety and Efficacy Evaluation of Intravitreal Injection of GMP-compliant Bone Marrow Mesenchymal Stem Cell-derived Small Extracellular Vesicles in Patients With Retinitis Pigmentosa
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Ophthalmological parameters
研究概览
简要总结
The aim of this clinical trials is to evaluate the safety and efficacy of intravitreal injection of GMP-compliant BM-MSC-derived sEVs in patients with retinitis pigmentosa.
详细描述
Inherited retinal disease (IRD) is one of the leading causes of blindness in adolescents and adults, affecting 1 in 2,000 to 3,000 people globally. Recently, advances arose in the use of stem cells as treatment modalities for inherited retinal diseases, including retinitis pigmentosa (RP).
The first step, production and characterization of GMP-compliant bone marrow mesenchymal stem cell (BM-MSC)-derived small extracellular vesicles (sEVs) has been performed according to the ethical clearance by the institutional review board of the Faculty of Medicine Siriraj Hospital Mahidol University (approval number Certificate of Approval (COA) no. Si 57112022, protocol number 44312565 (1RB1), dated August 8, 2022). In a prior study, the investigators have conducted a phase I clinical trial to assess the safety of intravitreal autologous MSC injection in 14 patients with advanced-stage RP. After follow-up periods ranging from 1.5 to 7 years, the investigators found that this intervention appeared to be safe and potentially effective. Nevertheless, several mild and one severe adverse event were observed, although all were manageable. Beside the primary outcome, safety of the MSCs, the investigators found statistically significant improvements in the best corrected visual acuity (BCVA) compared to baseline, although they returned to the baseline at 12 months. To minimize the unwanted effects and still maintain the benefit of the MSCs, the cell-free approach using the extracellular vesicles of MSCs is of interest.
On the current study, the investigators would like to evaluate the safety and efficacy of intravitreal injection of GMP-compliant BM-MSC-derived sEVs in patients with retinitis pigmentosa.
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
- •Age 18 years or above
- •Clinically diagnosed with RP by experienced ophthalmologists or having documented mutations in the genes responsible for RP
- •Central visual field in the better eye less than or equal to 20 degrees
- •Best corrected visual acuity (BCVA) in the worse eye 6/18 (logMAR 0.48) to 6/120 (logMAR 1.3) by Snellen visual acuity chart
- •Electroretinogram in the worse eye nonrecordable or the amplitudes were less than 25% of normal
- •Willing and able to give informed consent for participation in the study
排除标准
- •Intolerance and/or contraindication to local anesthesia and other substances used during the procedure
- •Pregnant or lactating woman
- •Having blood-borne infections, i.e. Human immunodeficiency virus (HIV), hepatitis B or C, Human T-lymphotropic viruses (HTLV)
- •Having any other significant ocular or non-ocular disease/disorder which may either put the subjects at risk because of participation in the study, or may influence the results of the study, or the subjects ability to participate in the study. This includes
- •Inherited or acquired bleeding disorders, including the use of anticoagulant medications that cannot be stopped prior the procedure
- •Autoimmune diseases, i.e., systemic lupus erythematosus, multiple sclerosis, fibromyalgia, Guillain-Barre syndrome
- •Severe/uncontrolled chronic/metabolic diseases, e.g., diabetes mellitus, cardiovascular disease, chronic kidney disease, transient ischemic attack (TIA)/stroke
- •Unable to complete the full course of the study or failed to return for follow up
研究组 & 干预措施
Bone marrow-mesenchymal stem cell-derived small extracellular vesicles
Single intravitreal injection of Good Manufacturing Practice (GMP) compliant bone marrow (BM)-mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) (50 μg) for single eye
干预措施: GMP compliant-BM-MSC derived sEVs (Biological)
结局指标
主要结局
Ophthalmological parameters
时间窗: 1 year
macular thickness in micron
Incidence of treatment-emergent adverse events
时间窗: 1 year
To evaluate the safety of the intervention. The evaluations include the intraocular pressure in mmHg, cell value in number of cells in 0.5 cubic millimeter and flare value in photons per millisecond, anterior segment examination using slit lamp biomicroscopy, fundus evaluation using fundus photography, retinal assessment, and subjective complaints of study participants.
次要结局
未报告次要终点