NCT00686868已完成1 期
Clinical Phase I/IIA Study of Subcutaneously Administration of Ofatumumab in Rheumatoid Arthritis Patients on Stable Dose Methotrexate
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Safety and tolerability as described by the incidence and severity of adverse events [AEs], clinical laboratory parameters and vital signs.
研究概览
简要总结
This study will examine the safety and tolerability, PK and PD of subcutaneously administered GSK1841157 in patients with RA on stable dose Methotrexate. The study comprises a single dose escalation/de-escalation phase to investigate the minimal efficacious dose based on PD markers with an acceptable safety profile.
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
- Single (Participant)
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
- •Male or female aged ≥ 18 years
- •A diagnosis of rheumatoid arthritis according to the American College of Rheumatology (ACR1987 classification) of at least six months prior to screening
- •Subjects must be treated with MTX, 7.5-25 mg/week, for at least 12 weeks prior to Visit 2, with the last 4 weeks prior to Day 2 at a stable dosage
- •Patient must be willing to receive folic acid ≥5mg/wk 4 weeks prior to baseline administered according to locally accepted practice
- •Body mass index (BMI) < 35kg/m2 (inclusive)
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
排除标准
- •Subjects with a history of a rheumatic autoimmune disease other than RA (except secondary Sjögren's syndrome), or with significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis or Felty's syndrome)
- •Previous exposure to biologic cell depleting anti-rheumatic therapies, including investigational compounds (e.g. anti-CD11a, anti-CD19, anti-CD20, anti-CD22, anti-BLyS/BAFF, anti-CD3, anti-CD4, anti-CD5, anti-CD52)
- •Exposure to etanercept < 4 weeks, infliximab or adalimumab < 8 weeks, or abatacept or anakinra < 12 weeks prior to visit 2
- •Received any of the following treatments within 4 weeks prior to Visit 2:
- •Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues, monoclonal antibodies)
- •Glucocorticoid unless given in doses equivalent to ≤ 10 mg of prednisolone /day
- •Intra-articular, i.m. or IV corticosteroids
- •Live/attenuated vaccinations
- •Cyclosporine
- •Azathioprine
- •Penicillamine
- •Sulfasalazine
- •Bucillamine
- •Hydroxychloroquine
- •Chloroquine
- •Exposure to leflunomide within 12 weeks prior to visit 2 unless the subject has completed peroral cholestyramine treatment
- •Exposure to gold therapy ≤ 12 weeks prior to Visit 2
- •Exposure to IV immunogammaglobulins ≤ 24 weeks prior to Visit 2
- •Past or current malignant melanoma
- •Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, renal infection, chest infection with bronchiectasis, tuberculosis and active hepatitis B and C
- •History of significant cerebrovascular disease
- •Positive plasma / white cell JC Virus (JCV) PCR (either compartment)
研究组 & 干预措施
0.3mg
Experimental
active
干预措施: ofatumumab (Drug)
placebo
Placebo Comparator
placebo
干预措施: placebo (Other)
3mg
Experimental
active
干预措施: ofatumumab (Drug)
30mg
Experimental
active
干预措施: ofatumumab (Drug)
60mg
Experimental
60mg
干预措施: ofatumumab (Drug)
100mg
Experimental
100mg
干预措施: ofatumumab (Drug)
结局指标
主要结局
Safety and tolerability as described by the incidence and severity of adverse events [AEs], clinical laboratory parameters and vital signs.
时间窗: throughout the study
次要结局
- Requirement for the use of pre-medication, including the timing, type and dose required.(throughout study)
- Pharmacodynamics (B-cell depletion and re-population) as measured by CD-19 peripheral blood B- lymphocyte count via routine fluorescent activated cell sorting (FACS) analysis.(throughout study)
- Immunoglobulins (IgA, IgG, IgM), Complement (CH50, C3, C4), IgM Rheumatoid Factor (IgM-RF), IgA-RF and IgG-RF, anti-cyclic citrullinated peptide antibody (aCCP),(throughout study)
- PK/PD parameters including estimation of time to re-population of CD-19 peripheral blood B-cells to above LLQ (and/or <95% depletion) following single subcutaneous dose of Ofatumumab.(throughout study)
- Immunogenicity as measured by the incidence, titre and type of human anti-human antibody (HAHA) immune response.(throughout study)
- Other pharmacodynamic/biomarkers of disease activity and immune status may include high sensitivity C-reactive protein (hsCRP), Erythrocyte Sedimentation Rate (ESR), B-Lymphocyte Stimulator (BLyS/BAFF), B-Lymphocyte Chemokine (BLC), IL-6,(throughout study)
- serum amyloid A (SAA), CD-3+, CD-4+ and CD-8+ lymphocytes or other biomarkers, as data permit.(throughout study)
- Pharmacodynamics (B-cell depletion and re-population) as measured by CD-19 peripheral blood B- lymphocyte count via routine FACS analysis.Other Secondary Endpoints(throughout study)
研究者
研究点 (1)
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