A Phase II, Double-Blind, Placebo-Controlled, Multi-Center, Randomized Withdrawal Design Trial Using Adaptive Randomization Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 294
- 试验地点
- 1
- 主要终点
- Change From Baseline in DAS28-CRP at 12 Weeks
研究概览
简要总结
Thus study will test an experimental drug called Z-102 (combination of prednisolone and dipyridamole) to treat patients with moderate to severe rheumatoid arthritis.
详细描述
The primary objective of the study was to demonstrate the efficacy of Z102 (2.7 mg prednisolone/360 mg dipyridamole) versus placebo on the Disease Activity Score 28 using C reactive protein (DAS28-CRP) in subjects with rheumatoid arthritis at the study endpoint of 12 weeks
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
- •Meet the ACR / EULAR criteria for classification of RA
- •Have moderate to severe RA, defined as involving a minimum (≥6 total swollen and ≥6 total tender) of the 28 joints assessed
- •Have screening CRP levels of at least 0.6 mg/dl and a DAS28-CRP score ≥4.5
- •Have been on a stable dose of conventional DMARD therapy for at least 90 days without dosage adjustment or modification and should be able to maintain the same dose of conventional DMARD therapy during study participation (with or without glucocorticoid therapy
排除标准
- •Treatment-refractory patients are excluded
- •Has active cardiovascular disease, unless well controlled by appropriate treatment for a minimum of 3 months prior to screening
- •Is taking aspirin for reasons other than for cardiovascular prophylaxis or their total daily dose is greater than 325 mg
- •Is currently taking steroids at a daily prednisone dose, or the equivalent, of >10 mg
- •Intraarticular, intramuscular, or intravenous glucocorticoids must not have been given at least 6 weeks prior to entering the study
- •The need to continue the use of one or multiple NSAID's at the same time, or the use of acetaminophen on a chronic basis
- •All opiate use is prohibited
- •Use of any other medications or herbs used for the treatment of pain is prohibited
- •Patients with a history of or currently active tuberculosis as per specific country guidelines are excluded
- •Has uncontrolled diabetes mellitus as defined by a serum glucose >126 mg/dl
- •Knowingly has HIV infection or hepatitis
- •Has undergone administration of any investigational drug within 30 days of study initiation
- •All biologic agents are excluded for 90 days prior to Screening and throughout the study.
- •Has undergone administration of rituximab or any B-cell depleting investigational drugs within 6 months of study initiation
- •Has had a history of alcohol or drug abuse within the past 2 years
- •Has a history of hypersensitivity to glucocorticoids and/or dipyridamole
研究组 & 干预措施
Prednisolone
Prednisolone 2.7 mg daily for 12 weeks
干预措施: Prednisolone (Drug)
dipyridamole
Dipyridamole 360 mg daily for 12 weeks
干预措施: dipyridamole (Drug)
prednisone
Prednisone 5 mg daily for 12 weeks
干预措施: Prednisone (Drug)
Z102 (2.7/360)
Prednisolone 2.7 mg plus dipyridamole 360 mg daily for 12 weeks
干预措施: Z102 (Drug)
placebo
Placebo daily for 12 weeks
干预措施: placebo (Other)
结局指标
主要结局
Change From Baseline in DAS28-CRP at 12 Weeks
时间窗: baseline to week 12
The primary efficacy endpoint was the mean change in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) from baseline to Week 12. The DAS28-CRP is a composite measure of inflammation in Rheumatoid Arthritis and incorporates a tender and swollen joint count, CRP and Patient Global Assessment of Disease Activity expressed in a Gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of \<3.2 suggests a low level of disease activity, while a score of \>5.1 suggests a high level of disease activity. Using the DAS-CRP as a continuous scale allows investigators (and clinicians) to measure a clinically meaningful endpoint following institution of a therapeutic intervention. In RA, clinical remission would therefore be graded as a DAS28 score of ≤3.2 with disease flare accompanying scores of ≥5.1; well-controlled disease is best characterized as fitting in between these two scores.
次要结局
- Multidimensional Assessment of Fatigue (MAF) at Week 12(week 12)
- Time to Failure (Days)(Baseline to 12 weeks)
- Change From Baseline in DAS28-CRP Individual Components at 12 Weeks(Baseline to week 12)
- Percentage of Subjects Achieving ACR20, ACR50 and ACR70 at 12 Weeks(Week 12)