NCT00665925已完成2 期
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of Two Doses of R935788 in Rheumatoid Arthritis Patients Failing to Respond to Methotrexate
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 457
- 试验地点
- 64
- 主要终点
- American College of Rheumatology 20 (ACR20) Response at 6 Months
研究概览
简要总结
The purpose of this study is to determine whether the Spleen Tyrosine Kinase (Syk) inhibitor, R935788 (R788), at a dose of 100 mg, orally, twice-a-day, and/or a dose of of 150 mg, orally, once-a-day is effective in the treatment of Rheumatoid Arthrits in patients who have had an inadequate clinical response to methotrexate.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Patients must give written informed consent by signing an IRB/EC-approved Informed Consent Form (ICF) prior to admission to this study.
- •Males and females, 18 years of age or older, with active RA for at least 6 months prior to Day 1 dosing.
- •Patients must have been receiving weekly methotrexate doses (7.5-25 mg/week) for a minimum of 3 months prior to Day 1 dosing and must be receiving a stable MTX dose, with no change in route, for the previous 6 weeks prior to Day 1 dosing.
- •'Patients must be receiving a folic or folinic acid supplementation at a stable dose for at least 6 weeks prior to Day 1 dosing.
- •Females of childbearing potential must be fully informed of the potential for R788 to adversely affect the fetus and, if sexually active, must agree to use a well established method of birth control during the study (oral contraceptive, mechanical barrier, long acting hormonal agent). These patients must not be lactating and must have a negative urine pregnancy test at the time of randomization and at each laboratory determination.
- •The patient must otherwise be in good health as determined by the Investigator on the basis of medical history, physical examination, and laboratory screening tests during the screening period. See exclusion criteria for specific exclusions.
- •In the Investigator's opinion, the patient has the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the Investigator and to participate in, and to comply with, the requirements of the entire protocol.
排除标准
- •The patient has a history of, or a concurrent, clinically significant illness, medical condition (other than arthritis) or laboratory abnormality that, in the Investigator's opinion, could affect the conduct of the study. Specifically, excluded are patients with the following:
- •uncontrolled or poorly controlled hypertension;
- •other autoimmune disease (psoriatic arthritis, lupus, mixed connective disorder) or arthritis syndromes (gout, Lyme disease, Reiter's syndrome);
- •recent (within past 2 months prior to Day 1 dosing) serious surgery or infectious disease;
- •recent history (past 5 years prior to Day 1 dosing) of, or treatment for, a malignancy other than nonmelanomatous skin cancer, or any history of lymphoma;
- •Hepatitis B ;
- •Hepatitis C ;
- •interstitial pneumonitis or active pulmonary infection on chest x-ray;
- •Tuberculosis (TB): the TB skin test should be negative.
- •known laboratory abnormalities.
- •The patient has a history of substance abuse, drug addiction or alcoholism. Patients may consume up to 4 units of alcohol per week; however, alcohol should be avoided in the 72 hours prior to lab assessments. Patients who cannot reliably comply with this should be excluded. A unit of alcohol is defined as the following: Beer=12 oz or 355 mL; wine = 5 oz or 148 mL; sweet dessert wine=3 oz or 89 mL; 80 proof distilled spirits= 1.5 oz or 44 mL.
- •The patient has been treated previously treated with R788 under a different protocol.
研究组 & 干预措施
1
Experimental
R788, 100 mg tablet, orally, twice-a-day
干预措施: Fostamatinib disodium (R935788) (Drug)
2
Experimental
R788, 150 mg tablet, orally, once a day
干预措施: Fostamatinib disodium (R935788) (Drug)
3
Placebo Comparator
Placebo, orally, either once a day, or twice a day
干预措施: Placebo (Drug)
结局指标
主要结局
American College of Rheumatology 20 (ACR20) Response at 6 Months
时间窗: 6 months
The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 6 months
次要结局
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 4 Months(4 months)
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 1 Month(1 month)
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 2 Months(2 months)
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 3 Months(3 months)
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 4 Months(4 months)
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 5 Months(5 months)
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 6 Months(6 months)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 1 Month(1 month)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 2 Months(2 months)
- American College of Rheumatology 20 (ACR20) Response at 1 Week(1 week)
- American College of Rheumatology 20 (ACR20) Response at 2 Weeks(2 weeks)
- American College of Rheumatology 20 (ACR20) Response at 1 Month(1 month)
- American College of Rheumatology 20 (ACR20) Response at 6 Weeks(6 weeks)
- American College of Rheumatology 20 (ACR20) Response at 2 Months(2 months)
- American College of Rheumatology 50 (ACR50) Response at 3 Months(3 months)
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 3 Months(3 months)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 3 Months(3 months)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 4 Months(4 months)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 5 Months(5 months)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 6 Months(6 months)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 1 Month(1 month)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 2 Months(2 months)
- American College of Rheumatology 50 (ACR50) Response at 4 Months(4 months)
- American College of Rheumatology 50 (ACR50) Response at 6 Months(6 months)
- American College of Rheumatology 70 (ACR70) Response at 1 Week(1 week)
- American College of Rheumatology 70 (ACR70) Response at 2 Weeks(2 weeks)
- American College of Rheumatology 70 (ACR70) Response at 1 Month(1 month)
- American College of Rheumatology 70 (ACR70) Response at 2 Months(2 months)
- American College of Rheumatology 70 (ACR70) Response at 4 Months(4 months)
- American College of Rheumatology Index of Improvement (ACRn) at 1 Month(1 month)
- American College of Rheumatology Index of Improvement (ACRn) at 2 Months(2 months)
- American College of Rheumatology Index of Improvement (ACRn) at 6 Months(6 months)
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 5 Months(5 months)
- American College of Rheumatology 50 (ACR50) Response at 5 Months(5 months)
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 6 Months(6 months)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 3 Months(3 months)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 4 Months(4 months)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 5 Months(5 months)
- Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 6 Months(6 months)
- Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at 6 Months(Baseline to 6 months)
- Short Form Health Survey (SF-36) Physical Component Summary (PCS) at 6 Months(Baseline to 6 months)
- Short Form Health Survey (SF-36) Mental Component Summary (MCS) at 6 Months(Baseline to 6 months)
- Alanine Aminotransferase (ALT) >1.5x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Alanine Aminotransferase (ALT) >1.5-2x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Alanine Aminotransferase (ALT) >2-3x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Alanine Aminotransferase (ALT) >3x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Alanine Aminotransferase (ALT) >3-5x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Alanine Aminotransferase (ALT) >5-10x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Alanine Aminotransferase (ALT) >10x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Aspartate Aminotransferase (AST) >1.5x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Aspartate Aminotransferase (AST) >1.5-2x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Aspartate Aminotransferase (AST) >2-3x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Aspartate Aminotransferase (AST) >3x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Aspartate Aminotransferase (AST) >3-5x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Aspartate Aminotransferase (AST) >5-10 x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Aspartate Aminotransferase (AST) >10 x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Alkaline Phosphatase >1.5 x Upper Limit of Normal (ULN) and >1.5 Times Baseline(Any time between baseline and 6 months)
- Bilirubin >1.5 x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Bilirubin >2 x Upper Limit of Normal (ULN)(Any time between baseline and 6 months)
- Absolute Neutrophil Count (ANC) <1500/mm3(Any time between baseline and 6 months)
- American College of Rheumatology 70 (ACR70) Response at 6 Weeks(6 weeks)
- American College of Rheumatology 70 (ACR70) Response at 3 Months(3 months)
- American College of Rheumatology Index of Improvement (ACRn) at 1 Week(1 week)
- American College of Rheumatology Index of Improvement (ACRn) at 2 Weeks(2 weeks)
- American College of Rheumatology Index of Improvement (ACRn) at 6 Weeks(6 weeks)
- American College of Rheumatology Index of Improvement (ACRn) at 3 Months(3 months)
- American College of Rheumatology Index of Improvement (ACRn) at 5 Months(5 months)
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 2 Months(2 months)
- Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 1 Month(1 month)
- American College of Rheumatology 20 (ACR20) Response at 3 Months(3 months)
- American College of Rheumatology 20 (ACR20) Response at 4 Months(4 months)
- American College of Rheumatology 20 (ACR20) Response at 5 Months(5 months)
- American College of Rheumatology 50 (ACR50) Response at 1 Week(1 week)
- American College of Rheumatology 50 (ACR50) Response at 2 Weeks(2 weeks)
- American College of Rheumatology 50 (ACR50) Response at 1 Month(1 month)
- American College of Rheumatology 50 (ACR50) Response at 6 Weeks(6 weeks)
- American College of Rheumatology 50 (ACR50) Response at 2 Months(2 months)
- American College of Rheumatology 70 (ACR70) Response at 5 Months(5 months)
- American College of Rheumatology 70 (ACR70) Response at 6 Months(6 months)
- American College of Rheumatology Index of Improvement (ACRn) at 4 Months(4 months)
研究者
研究点 (64)
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