A Double-blind, Randomized, Placebo Controlled, Dose Escalation, Multi-centerphase I/II Trial of HuMax-CD20, a Fully Human Monoclonal Anti-CD20antibody, in Patients With Active Rheumatoid Arthritis Who Have Previously Failedone or More Disease Modifying Anti-rheumatic Drugs
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 201
- 主要终点
- To evaluate the safety of HuMax-CD20 in patients with active rheumatoid arthritis
研究概览
简要总结
The purpose of this trial is primarily to investigate the safety profile of HuMax-CD20 in patients with active RA. Furthermore, the trial is designed to identify the dose levels to be used in future trials (based on evaluations of safety, pharmacokinetics and ACR and DAS responses).
详细描述
This trial consists of a double-blind, placebo controlled, dose escalation part with randomization to trial treatment within each of three sequential cohorts (Part A), and a parallel group part with randomization into one of four treatment arms (Part B). Patients in Parts A and B will receive two infusions of either HuMax-CD20 (300 mg, 700 mg, or 1000 mg) or placebo and will be followed for safety, efficacy, and pharmacokinetic measurements for 24 weeks. Hereafter patients will be followed every 12 weeks until B-cells (CD19+ cells) have returned to baseline levels. For patients in Part B, the follow-up visits at 36 and 48 weeks after initial trial treatment (Follow-up Visits 1 and 2) will include additional measurements of safety and efficacy.
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
- 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
- •Age ≥ 18 years
- •Active rheumatoid arthritis according to the American College of Rheumatology of at least six months duration with six or more swollen and six or more tender joints (of 28 joints) and Erythrocyte Sedimentation Rate (ESR) ≥ 22 mm/h and/or C-Reactive Protein (CRP) ≥ 10 mg/L (1 mg/dL).
- •Treatment failure to one or more DMARDs.
- •Treatment with methotrexate (7.5-25 mg/wk) for at least 12 weeks and at a stable dose for at least 4 weeks prior to planned start of trial treatment.
排除标准
- •Use of DMARDs other than methotrexate.
- •Current or previous (within four weeks of screening) participation in any other clinical trial.
- •Previous exposure to other biological products within 4 weeks prior to planned start of trial treatment, and/or exposure to anti-CD20 antibodies within two years before screening for this trial.
- •Any use of cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents within five years before screening for this trial.
- •Active autoimmune disease (other than RA and RA-associated secondary diseases) requiring immunosuppressive therapy.
- •Past or current malignancy, except for resected cervical carcinoma Stage 1B or less, non-invasive basal cell and squamous cell skin carcinoma, malignant melanoma with a complete response of a duration of > 10 years, or other cancer diagnoses with a complete response of a duration of > 5 years.
- •Chronic or current infectious disease including known or suspected positive serology for HIV, hepatitis B, or hepatitis C.
- •Clinically significant cardiac disease, or history of significant cerebrovascular disease.
- •Significant concurrent, uncontrolled medical condition including, but not limited to: renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease.
- •Breast feeding women, women with a positive pregnancy test at screening, or women of childbearing potential not willing to use adequate contraception during the trial.
研究组 & 干预措施
Dose ranging
A double-blind, placebo controlled, dose escalation part randomized within each of 3 sequential cohorts (Part A),
干预措施: Part A (Drug)
Parallel Arm RCT
a parallel group part with randomization into one of 4 treatment arms (Part B).
干预措施: Part B (Drug)
结局指标
主要结局
To evaluate the safety of HuMax-CD20 in patients with active rheumatoid arthritis
时间窗: 24 weeks
To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 12 to 24 weeks after initiation of treatment
时间窗: 24 weeks
次要结局
- To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 36 & 48 weeks after initiation of treatment(48 weeks)
- To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis by measuring the degree and duration of B-cell depletion(24 weeks)
- To determine the pharmacokinetic profile of HuMax-CD20 in patients with active rheumatoid arthritis(24 weeks)
- To determine host immune response, Human Anti Human Antibodies (HAHA), against HuMax-CD20(24 weeks)
- To evaluate if Fc-receptor polymorphism influences the safety and efficacy of HuMax-CD20 in patients with active rheumatoid arthritis(24 weeks)