Phase III, Multicenter, Randomized, Open-label Clinical Trial Comparing Treatment with Allogeneic Mesenchymal Cells Versus Autologous Mesenchymal Cells and Versus Active Control with Hyaluronic Acid in Patients with Knee Osteoarthritis
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 124
- 试验地点
- 8
- 主要终点
- Range of motion.
研究概览
简要总结
Phase III, multicenter, randomized, open-label, multicenter clinical trial comparing treatment with allogeneic mesenchymal cells versus autologous mesenchymal cells and versus active control with hyaluronic acid in patients with knee osteoarthritis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gonarthrosis grade 2, 3 or 4 of Kellgren and Lawrence (Kellgren & Lawrence, 1957) assessed by two observers.
- •Chronic painful knee of mechanical characteristics.
- •Absence of local or systemic septic process.
- •Hemat imetric and biochemical analysis without significant alterations that contraindicate the treatment.
- •Written informed consent of the patient.
- •The patient is able to understand the nature of the study.
- •Body Mass Index 20-35 Kg/m2.
排除标准
- •Patient < 18 years old, or legally dependent.
- •Patient > 75 years old.
- •Congenital or developmental diseases that translate malformation and / or significant deformations of the knee (varus>10º; valgus>20º) and condition difficulties of application and evaluation of the results.
- •Pregnant or breastfeeding women.
- •Neoplastic disease.
- •Intra-articular infiltration of any drug in the 3 months prior to study inclusion.
- •Concurrent participation in another clinical trial or treatment with another investigational product within 30 days prior to study enrollment.
- •Allergy to gentamicin (antibiotic used in the cell culture process ).
- •Other diseases or circumstances that compromise participation in the study according to medical criteria.
研究组 & 干预措施
Autologous Mesenchymal Stromal Cells (MSC)
Treatment with 40 millions of autologous autologous adult mesenchymal stem cells from expanded bone marrow administered intra-articularly.
干预措施: Autologous MSCs (Drug)
Allogenic Mesenchymal Stromal Cells (MSC)
Treatment with 40 millions of adult allogeneic expanded bone marrow mesenchymal stem cells administered intra-articularly.
干预措施: Allogenic MSCs (Drug)
Active Control
Hyaluronic Acid 60mg/3ml administered intra-articularly.
干预措施: Hyaluronic Acid (Drug)
结局指标
主要结局
Range of motion.
时间窗: 12 months
Evaluation of clinical-functional response using Joint range-of-motion evaluation (Flexion score 0º-140º / Extension score -140º-0º / Hyperextension: positive degrees from 0).
Pain self-assessment.
时间窗: 12 months
Evaluation of pain using Visual Analogue Scale (VAS) (Pain self-assessment score range from 0 -no pain- to 10 -maximum-).
Radiological response using nuclear magnetic resonance imaging.
时间窗: 12 months
Evaluation of radiological response using T2 mapping nuclear magnetic resonance imaging (screening visit global mean of T2 values versus 12 months visit global mean of T2 values).
Knee Osteoarthritis.
时间窗: 12 months
Evaluation of Knee Osteoarthritis using Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) \[measures five items for pain (score range from 0 -no pain- to 20 -maximum-), two for stiffness (score range from 0-no stiffness- to 8 -maximum-), and 17 for functional limitation (score range from 0 -no limitation- to 68 -maximum-)\]
Functional response.
时间窗: 12 months
Evaluation of functional response using Lequesne Algofunctional Index (score range from 0 to 24). It includes measures of pain (5 questions), walking distance (1 question) and activities of daily living (4 questions) with separate versions for the hip and knee. The scores for each question are summed to obtain a combined score of disease severity. Scores 1 to 4 are classified as mild osteoarthrosis; 5 to 7, moderate; 8 to 10, severe; 11 to 13, very severe; and 14 and above, extremely severe.
X-ray changes of osteoarthritis.
时间窗: 12 months
Radiological response using Kellgren and Lawrence classification system (grade from 0 to 4): * grade 0 (none): definite absence of x-ray changes of osteoarthritis. * grade 1 (doubtful): doubtful joint space narrowing and possible osteophytic lipping. * grade 2 (minimal): definite osteophytes and possible joint space narrowing. * grade 3 (moderate): moderate multiple osteophytes, definite narrowing of joint space and some sclerosis and possible deformity of bone ends. * grade 4 (severe): large osteophytes, marked narrowing of joint space, severe sclerosis and definite deformity of bone ends.
次要结局
- Feasibility assessment of a multicentre strategy production of both cell types with several Cell Production Units(24 months)
- Evaluate induced changes in circulating cells of the immune system after cell treatment (exploratory objetive)(30 days)
- Perceived general well-being.(6, 12 and 24 months)
- Evaluation of presence of adverse events related with investigational medical product (IMP).(24 months)
- Evaluation of products obtained by genomic study and potency studies of the final products of all cell types (exploratory objective)(30 days)