A Randomized, Double Blind, Placebo-controlled Pilot-study to Evaluate Efficacy and Safety of Low-dose hrIL-2 in the Treatment of Methotrexate (MTX)-Naive Patients With Rheumatoid Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Percentage of Participants Achieving DAS28 Remission.
研究概览
简要总结
Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, characterized by symmetric poly-arthritis usually involving the small joints of the hands and feet. In addition, various extra-joint manifestations may develop. Several immunomodulating agents have been attempted in the treatment of RA without achieving satisfactory results. Dysfunction of regulatory T (Treg) cells has been detected in diverse autoimmune diseases, which can be promoted by interleukin-2 (IL-2). The investigators hypothesized that low-dose IL-2 could be a novel therapy in active RA patients. This clinical study will test the efficacy and safety of low dose IL-2 treatment in RA. The investigators perform a single-centre, double-blind pilot trial with hrIL-2 in RA. The investigators evaluate the effectiveness and safeness of low-dose hrIL-2 for RA by randomized controlled study (hrIL-2 (N = 23) + Methotrexate (MTX)+ Loxoprofen versus placebo+MTX + Loxoprofen group (N = 24)).
详细描述
Each RA patients (n=47) with DAS>3.2 received low-dose IL-2+MTX+ Loxoprofen or placebo+MTX + Loxoprofen (active group: placebo group =1:1, 1 million units every other day subcutaneously (hrIL-2 1×106, ip, Qod) for a period of 14 days. After a 14-day rest, another cycle started) for 3 cycles. The end points were safety and clinical and immunologic response.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥18 and ≤70 years of age at time of screening
- •Diagnosed with rheumatoid arthritis
- •Must have active disease with DMARDs (Disease Modifying Anti-Rheumatic Drugs) except MTX, the doses had been stable for at least 3 months before baseline
- •Moderate or severe rheumatoid arthritis during screening, as defined by a disease activity score (28 joint) calculated using the C-reactive protein formula (DAS28-ESR) > 3.2
- •Have given written informed consent
排除标准
- •Patient presenting or having a history of other inflammatory joint disease
- •Patient with ongoing or previous Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme
- •Patient with significantly impaired bone marrow function or significant anaemia, leucopenia or thrombocytopenia due to causes or other than active rheumatoid arthritis
- •Persistent infection or severe infection within 3 months before enrollment,
- •Uncontrolled hypertension, uncontrolled diabetes, unstable ischemic heart disease, active inflammatory bowel disease, active peptic ulcer disease, terminal illness or other medical condition which, in the opinion of the investigator, would put the patient at risk to participate in the study,
- •Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult
- •Severe hypoproteinemia (e.g., in case of severe liver disease or nephrotic syndrome) with serum albumin < 30 g/L
- •Moderate or severe impairment of renal function, as known by serum creatinine > 133μmol/L (or 1.5 mg/dl)
- •Patient with history of recent and clinically significant drug or alcohol abuse
- •Impairment of liver function or persisting ALT (SGPT) elevations of more than 2-fold the upper limit of normal
- •Known HIV positive status
- •Known positive serology for hepatitis B or C
- •Patient with hypersensitivity to any of the excipients in the tablets of methotrexate
- •Pregnancy
- •Breastfeeding
- •Women of childbearing potential, except if they fulfill specific conditions,
- •Men wishing to father children during the course of the study or within the 24 months thereafter (or 3 month with the washout procedure)
- •Patient with a congenital or acquired severe immuno-deficiency, a history of cancer or lymphoproliferative disease, or any patient who has received total lymphoid irradiation.
- •Enrollment in any other clinical trial involving off-label use of an investigational drug or device, or enrollment in any other type of medical research
- •Any active infection (including chronic or localized infections) for which anti-infectives were indicated within 28 days prior to first investigational product dose
- •BMI(body mass index) under 18.5 kg/m2 or more than 30 kg/m2
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Experimental
hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen
干预措施: hrIL-2 active (Drug)
Experimental
hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen
干预措施: MTX (Drug)
Experimental
hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen
干预措施: Folic Acid (Drug)
Experimental
hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen
干预措施: Loxoprofen (Drug)
Placebo Comparator
hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen
干预措施: hrIL-2 placebo (Drug)
Placebo Comparator
hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen
干预措施: MTX (Drug)
Placebo Comparator
hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen
干预措施: Folic Acid (Drug)
Placebo Comparator
hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen
干预措施: Loxoprofen (Drug)
结局指标
主要结局
Percentage of Participants Achieving DAS28 Remission.
时间窗: week 24
DAS 28 remission is defined by a disease activity score (28 joint) calculated using the erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6
Percentage of Participants Meeting the American College of Rheumatology 20% Response Criteria
时间窗: week 12, week 24
The assessments are based on a 20% or greater improvement from Baseline in the number of tender joints, a 20%, or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
The Change From Baseline of Clinical Disease Activity Index (CDAI)
时间窗: week 12, week 24
Clinical Disease Activity Index(CDAI), the minimum is 0, the maximum is 76. higher scores mean a worse outcome. The change of from baseline of CDAI, the minimum is -76, the maximum is 76. higher scores mean a worse outcome.
The Change From Baseline of Simplified Disease Activity Index (SDAI)
时间窗: week 12, week 24
Simplified Disease Activity Index(SDAI). the minimum is 0, the maximum is 96. higher scores mean worse outcome. The change from baseline of SDAI. the minimum is -96, the maximum is 96. higher scores mean worse outcome.
次要结局
- Percentage of Participants Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response(week 12, week 24)
- Percentage of Participants Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice(week 12, week 24)
- Number of Participants With Adverse Events(Up to week 24)
- Percentage of Participants Meeting the American College of Rheumatology 70% Response Criteria(week 12, week 24)
- The Change From Baseline of a Health Assessment Questionnaire- Disability Index (HAQ-DI)(week 12, week 24)
- Percentage of CD4+ Treg Cells(week 12, week 24)
- Erythrocyte Sedimentation Rate (ESR)(week 12, week 24)
- C Reactive Protein (CRP)(week 12, week 24)
- The Change From Baseline of Physician's Global Assessment of Disease Activity (PhGADA)(week 12, week 24)
- Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]-2(week 24)
- Percentage of Participants Achieving DAS28 Low Disease Activity.(week 12, week 24)
- The Scores of SF-36 Quetionnaire(week 12, week 24)
- Work Productivity Survey - Rheumatoid Arthritis [WPS-RA](week 24)
- The Change From Baseline of Patient's Assessment of Arthritis Pain (PtAAP)(week 12, week 24)
- Percentage of Participants Meeting the American College of Rheumatology 50% Response Criteria(week 12, week 24)
- The Change From Baseline of Patient's Global Assessment of Disease Activity (PtGADA)(week 12, week 24)
研究者
Zhanguo Li
Dept. Rheumatology and immunology,Peking University People's Hospital
Peking University People's Hospital