A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Preliminary Clinical Activity and Immunogenicity of Multiple Doses of MOR103 Administered Intravenously to Patients With Active Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- MorphoSys AG
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Percentages of Patients With Treatment-emergent or Serious Adverse Events
研究概览
简要总结
GM-CSF is considered to have a key role in the initiation and progression of arthritic inflammation. The purpose of this study is to evaluate the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of multiple doses of MOR103, a human antibody to GM-CSF, in patients with active rheumatoid arthritis.
详细描述
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects 0.5% to 1% of the adult population world wide. RA primarily affects the joints and is characterized by chronic inflammation of the synovial tissue, which eventually leads to the destruction of cartilage, bone and ligaments and can cause joint deformity.
Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), interleukin (IL)-1, IL-6 and granulocyte macrophage colony stimulating factor (GM-CSF), which lead to the activation and proliferation of immune cells, are found to be increased in the inflamed joint. Several preclinical findings support an anti-GM-CSF therapy for RA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Rheumatoid arthritis (RA) per revised 1987 ACR criteria
- •Active RA: ≥3 swollen and 3 tender joints with at least 1 swollen joint in the hand, excluding the PIP joint
- •CRP > 5.0 mg/L (RF and anti-CCP seronegative); CRP >2 mg/l (RF and/or anti-CCP seropositive)
- •DAS28 ≤ 5.1
- •Stable regimen of concomitant RA therapy (NSAIDs, steroids, non- biological DMARDs).
- •Negative PPD tuberculin skin test
排除标准
- •Previous therapy with B or T cell depleting agents other than Rituximab (e.g. Campath). Prior treatment with Rituximab, TNF-inhibitors, other biologics (e.g. anti-IL-1 therapy) and systemic immunosuppressive agents is allowed with a washout period.
- •Any history of ongoing, significant or recurring infections
- •Any active inflammatory diseases other than RA
- •Treatment with a systemic investigational drug within 6 months prior to screening
- •Women of childbearing potential, unless receiving stable doses of methotrexate or leflunomide
- •Significant cardiac or pulmonary disease (including methotrexate- associated lung toxicity)
- •Hepatic or renal insufficiency
研究组 & 干预措施
Group 1: MOR103, experimental
Biological: MOR103 0.3 mg/kg or placebo
干预措施: MOR103 (Drug)
Group 2: MOR103, experimental
Biological: MOR103 1.0 mg/kg or placebo
干预措施: MOR103 (Drug)
Group 3: MOR103, experimental
Biological: MOR103 1.5 mg/kg or placebo
干预措施: MOR103 (Drug)
结局指标
主要结局
Percentages of Patients With Treatment-emergent or Serious Adverse Events
时间窗: From the first dose through the 16-week visit
Data on treatment-emergent adverse events (MedDRA version 13.0) were collected at each visit (weeks 1, 2, 3, 4, 5, 6, 8, 10, 13, and 16). For a list of serious adverse events and adverse events occurring at a frequency of \>5 % (\>1 patient) in any treatment group, please see the adverse events listing.
次要结局
- Percentages of Subjects With American College of Rheumatology 20% Improvement (ACR20) at Week 4(Week 4 (1 week after last MOR103 dose))
- Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8(Change from baseline to week 4 (1 week after last MOR103 dose) and change from baseline to week 8)
- Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8(Change from baseline at week 4 (1 week after last MOR103 dose) and change from baseline at week 8)
- Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 4 Weeks(Change from baseline to week 4 (1 week after last MOR103 dose))
- Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 8 Weeks(Change from baseline to week 8 (5 weeks after last MOR103 dose))