Safety/Efficacy of Intra-articular Administration of Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Number of Participants experiencing AEs and SAEs following the intra-articular administration of tDCs.
研究概览
简要总结
Tolerogenic dendritic cell (tDC)-based clinical trials for the treatment of autoimmune diseases are now a reality. Clinical trials are currently exploring the effectiveness of tDC to treat of type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis and Crohn's disease. The general objective of this study is to evaluate the safety and tolerability of a single intra-articular injection (into the knee joint) of autologous monocyte-derived dendritic cells generated in the presence of interferon-alpha (IFN-α)/granulocyte-macrophage colony-stimulating factor (GM-CSF) and tolerized with Dexamethasone in rheumatoid arthritis (RA) patients.
详细描述
A phase I dose-escalating clinical trial will be conducted to determine the safety and tolerability of a single intra-articular injection (into the knee joint) of autologous tolerogenic dendritic cells, and to enable selection of a suitable dose regimen for phase II trial. The primary objective of the phase I study will be to determine whether tDC-based therapy is safe and well tolerated and to establish the dose-response with disease activity measured over 6 months. Patients will serve as their own controls (pre- and post-treatment). Five doses of tDCs will be tested. The Study will start with intra-articular injection (into the knee joint) of 1x106 cells. Depending on safety/tolerability outcomes, the dose will gradually increase to 3x106, 5x106, 8x106 and 10x106 cells. The safety will be determined by the evaluation of the number of participants with adverse events (AEs) and severe adverse events (SAEs) following the intra-articular administration of tDC (within 6 months of injection). Systemic RA disease activity will be measured using DAS28 (Disease Activity Score using 28 joints) and the Health Assessment Questionnaire (HAQ), a standard instruments used in RA. Patients will be monitored at baseline and at 3, 7 days and 1, 3, 6 months post treatment.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 75 Years
- •Patients with moderate to severe active RA (DAS28 >=3.2)
- •At least 6 month's disease duration
- •Synovitis of large joints (knee, elbow)
- •Morning stiffness in the target joint ≥ 30 minutes
- •Stable dose of disease-modifying anti-rheumatic drugs (DMARD) for ≥16 weeks
- •Patients must be able to tolerate all study procedures
- •Patients must be willing to voluntarily give written Informed Consent to participate in the study before any procedures are performed
- •Patients must be willing to be available for all baseline, treatment and follow-up examinations required by protocol
排除标准
- •Injection of target joint with glucocorticoids within 6 weeks of baseline
- •Known hypersensitivity to gentamicin or local anaesthetics
- •Dementia, psychiatric disorders
- •Renal dysfunctions
- •Hemodynamic or respiratory instability
- •HIV or uncontrolled bacterial, fungal, or viral infections
- •Pregnancy
- •Malignancy
- •Participation in other clinical trials
研究组 & 干预措施
tolerogenic dendritic cells
Each dose of autologous monocyte-derived dendritic cells generated in the presence of IFN-α/GM-CSF and tolerized with Dexamethasone (1x106, 3x106, 5x106, 8x106 and 10x106 cells in 2.0 mL sodium chloride 0.9% solution) will be administered in RA patients through intra-articular injection (into the knee joint).
干预措施: tolerogenic dendritic cells (Biological)
结局指标
主要结局
Number of Participants experiencing AEs and SAEs following the intra-articular administration of tDCs.
时间窗: within 6 months of injection
Occurrence and severity of adverse events following the intra-articular administration of tDCs will be evaluated within 6 months of injection.
次要结局
- Number of Participants Who Rated the Study and its Components as Partly or Completely Acceptable.(At final study visit, 6 months post treatment)
- Change from Baseline in the Health Assessment Questionnaire (HAQ)(Baseline, 1, 3 and 6 months post treatment)
- Change from Baseline in DAS28 Score.(Baseline, 1, 3 and 6 months post treatment)
研究者
Alexander A Ostanin
Head of Clinical Department
Russian Academy of Medical Sciences