A Randomized, Double-Blind, Placebo-Controlled, Phase II, Multi-Center Study for Treatment of Lupus Nephritis by Inhibition of Tumor Necrosis Factor-alpha Using Etanercept
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 6
- 主要终点
- Number of Adverse Events (AEs)Grade 3 or Higher Experienced by Participant During Treatment Phase of Study
研究概览
简要总结
Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease in which the body's immune system attacks its own normal tissues. This abnormal autoimmune response can result in damage to many parts of the body, including the skin, joints, lungs, heart, brain, intestines, and kidneys. Kidney problems occur in 60-75 % of lupus patients. The development of lupus-related kidney disease (called lupus nephritis) is associated with an overall worse prognosis.
SLE is usually treated with drugs that try to block inflammation caused by the immune system. These treatments can create their own problems and they do not cure lupus. The drugs that are often used to treat lupus nephritis include prednisone (steroids), cyclophosphamide (Cytoxan), azathioprine (AZA or Imuran), and mycophenolate mofetil (MMF or Cellcept). The main purpose of this study is to evaluate the safety and tolerability of etanercept compared to placebo in combination with standard of care to treat individuals with active lupus nephritis.
详细描述
Kidney problems associated with lupus nephritis range from asymptomatic protein in the urine to rapidly progressive glomerulonephritis, leading to end-stage renal disease. The goal of therapies is to control kidney manifestations in order to avoid kidney failure, the occurrence of other medical problems and death.
The treatment of lupus nephritis remains problematic. Despite the use of currently available therapies, patients experience disease relapse. Over time, patients develop significant morbidity from the disease as well as from medications used for treatment.
Etanercept, a TNF inhibitor, is proposed as a potential treatment for lupus nephritis. TNF increases the number of reactive B and T cells. TNF levels can be elevated in lupus. Etanercept is believed to work by blocking inflammation, and it is hoped that it will lessen the signs and symptoms of lupus-related kidney disease.
The purpose of this study is to evaluate the safety and tolerability of etanercept compared to placebo in combination with standard therapy to treat individuals with mild or moderately active lupus nephritis.
This study will last 1 year. Participants will be randomly assigned to receive either etanercept or placebo in addition to their regular medications. Participants will self-administer 50 mg etanercept or placebo injections once a week. They will continue receiving their usual treatment with corticosteroids and either MMF, Mycophenolic Acid, or AZA. Treatment with study medication will occur for 24 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
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets at least 4 of the 11 American College of Rheumatology (ACR) 1982 Revised Criteria for the Classification of SLE
- •Active lupus nephritis
- •Currently has antibodies to double-stranded DNA (dsDNA)
- •Currently receiving treatment consisting of at least 1.5 g/day of MMF OR at least 720 mg/day orally of Mycophenolic Acid OR at least 1.5 mg/kg once per day of AZA for lupus nephritis, for at least 28 days prior to study entry
- •Stable medication regimen for at least 4 weeks prior to study entry
- •Able and willing to self-administer study drug OR has a designated caregiver at home to administer study drug injections
- •Willing to use acceptable forms of contraception for the duration of the study
排除标准
- •Moderately severe anemia
- •Neutropenia
- •Thrombocytopenia
- •Blood creatinine levels greater than 3.0 mg/dl
- •Positive PPD without ongoing treatment for at least 30 days prior to study entry
- •Pulmonary fibrotic changes
- •Active infections (e.g., HIV, hepatitis B virus [HBV], hepatitis C virus [HCV]) and/or serologic evidence of prior exposure to hepatitis B
- •Received a live vaccine within 3 months prior to study entry
- •Doubled serum creatinine levels within the 3 months prior to study entry OR end-stage kidney disease
- •Dialysis-dependent end-stage kidney disease or membranous nephritis
- •History of cancer. Individuals with a history of cervical carcinoma in situ and resected basal and squamous cell carcinomas of the skin are not excluded.
- •Receiving prednisone greater than 20 mg/day or equivalent corticosteroid treatment
- •Pulse intravenous methylprednisolone within 30 days prior to study entry
- •Receiving immunosuppressive agents other than prednisone, MMF, Mycophenolic Acid, AZA, or hydroxychloroquine
- •Oral or intravenous cyclosporine, leflunomide IVIG, or plasmapheresis within 3 months prior to study entry
- •Current or previous cyclophosphamide treatment
- •Use of other experimental agent within 90 days prior to study entry
- •Severe, progressive, or uncontrolled kidney, liver, blood, stomach, lung, heart, or brain disease. Individuals with any of these conditions that are related to active SLE are not excluded.
- •Previous use of rituximab within 12 months prior to study entry
- •Previous or current exposure to any of the following: etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade), or anakinra (Kineret)
- •Meets New York Heart Association classification of congestive heart failure (CHF) Class III or greater
- •History of myocardial infarction or ischemia
- •Current or history of substance abuse
- •Known hypersensitivity to any component of the study drug
- •Poorly controlled or advanced diabetes mellitus
- •History of multiple sclerosis, transverse myelitis, optic neuritis, or epilepsy
- •History of noncompliance with other therapies
- •Pregnancy or breastfeeding
研究组 & 干预措施
Etanercept
Participants in this group will self-administer 50 mg etanercept injections once a week for 24 weeks. They will continue receiving their usual treatment with corticosteroids and either mycophenolate mofetil (MMF), mycophenolic acid, or azathioprine (AZA).
干预措施: Etanercept (Drug)
Etanercept
Participants in this group will self-administer 50 mg etanercept injections once a week for 24 weeks. They will continue receiving their usual treatment with corticosteroids and either mycophenolate mofetil (MMF), mycophenolic acid, or azathioprine (AZA).
干预措施: Lupus Treatment- Standard of Care (Drug)
Placebo
Participants in this group will self-administer 50 mg placebo injections once a week for 24 weeks. They will continue receiving their usual treatment with corticosteroids and either mycophenolate mofetil (MMF), mycophenolic acid, or azathioprine (AZA).
干预措施: Lupus Treatment- Standard of Care (Drug)
Placebo
Participants in this group will self-administer 50 mg placebo injections once a week for 24 weeks. They will continue receiving their usual treatment with corticosteroids and either mycophenolate mofetil (MMF), mycophenolic acid, or azathioprine (AZA).
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Adverse Events (AEs)Grade 3 or Higher Experienced by Participant During Treatment Phase of Study
时间窗: 24 Weeks
Number of adverse events (AEs) or serious adverse events (SAEs) Grade 3 or higher experienced by participant over the duration of the treatment period. \[1\] \[1\] This study graded the severity of AEs experienced by the study participant according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0.
次要结局
- Number of Participant Adverse Events (AEs) From Baseline to Early Study Withdrawal Visit(39 Weeks)
- Percent of Participants Who Achieved a Renal Response at Week 24(Week 24)
- Time to Participant's Renal Response(First 24 Weeks of Study Period)
- Participant Systematic Lupus Erythematosus Disease Activity Index (SLEDAI) Score at Baseline and at Early Study Withdrawal Visit(Baseline, Week 39 (Early Study Withdrawal Visit))
- Number of Participants With a C to B Score Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Mucocutaneous Score(Baseline, Week 24)
- Number of Participants With a B to D Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Musculoskeletal Score(Baseline, Week 24)
- Number of Participants With an A to B Score Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Renal Score(Baseline, Week 24)
- Participant Medical Outcome Study Short-Form 36 (SF-36) Physical Component Score at Baseline and Week 24(Baseline, Week 24)
- Participant Medical Outcome Study Short Form 36 (SF-36) Mental Component Score at Baseline and Week 24(Baseline, Week 24)