A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Belimumab Plus Standard of Care Versus Placebo Plus Standard of Care in Adult Subjects With Active Lupus Nephritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 448
- 试验地点
- 1
- 主要终点
- Open-label Period: Number of Participants Reporting Adverse Events of Special Interest (AESI)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, safety, and tolerability of belimumab in adult patients with active lupus nephritis.
详细描述
Study participants receive standard therapy (induction and maintenance) for lupus nephritis in addition to receiving either placebo (no active medicine) or belimumab. Induction therapy starts before the first dose of study drug (belimumab or placebo). Maintenance therapy begins after completion of induction therapy and continues for the remainder of the study. Participants receive study drug throughout the entire study, during both induction and maintenance periods. The controlled period of the study is 104 weeks. The random assignment in this study is "1 to 1" which means you have an equal chance of receiving treatment with belimumab or placebo. Participants who successfully complete the 104-week study may enter into a 6-month open-label extension. All participants in the open-label extension receive belimumab.
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
- •Clinical diagnosis of SLE by American College of Rheumatology (ACR) criteria.
- •Biopsy confirmed active lupus nephritis.
- •Clinically active lupus renal disease at screening requiring /receiving induction therapy with Standard of Care medications.
- •Autoantibody-positive.
排除标准
- •Pregnant or nursing.
- •On dialysis within the past year.
- •Treatment with belimumab within the past year .
- •Receipt of induction therapy with cyclophosphamide within 3 months prior to induction therapy for the study.
- •Receipt of any B cell targeted therapy (for example, rituximab), investigational biological agent within the past year.
- •Severe active central nervous system (CNS) lupus.
- •Required management of acute or chronic infections within the past 60 days.
- •Current drug or alcohol abuse or dependence.
- •Tested positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
- •History of severe allergic reaction to contrast agents or biological medicines.
研究组 & 干预措施
Placebo plus standard therapy
Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and then every 28 days thereafter through Week 100, with a final evaluation at Week 104 in the double-blind period. In the open-label extension period, placebo patients who opt to participate will receive belimumab 10 mg/kg IV every 28 days for an additional 6 months.
干预措施: Placebo plus standard therapy (Biological)
Placebo plus standard therapy
Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and then every 28 days thereafter through Week 100, with a final evaluation at Week 104 in the double-blind period. In the open-label extension period, placebo patients who opt to participate will receive belimumab 10 mg/kg IV every 28 days for an additional 6 months.
干预措施: Standard therapy (Drug)
Belimumab 10 mg/kg plus standard therapy
Belimumab 10 mg/kg IV plus standard therapy; belimumab administered on Days 0, 14, 28, and then every 28 days thereafter through Week 100, with a final evaluation at Week 104 in the double-blind period. In the open-label extension period, patients who opt to participate will continue to receive belimumab 10 mg/kg IV every 28 days for an additional 6 months.
干预措施: Belimumab 10 mg/kg plus standard therapy (Biological)
Belimumab 10 mg/kg plus standard therapy
Belimumab 10 mg/kg IV plus standard therapy; belimumab administered on Days 0, 14, 28, and then every 28 days thereafter through Week 100, with a final evaluation at Week 104 in the double-blind period. In the open-label extension period, patients who opt to participate will continue to receive belimumab 10 mg/kg IV every 28 days for an additional 6 months.
干预措施: Standard therapy (Drug)
结局指标
主要结局
Open-label Period: Number of Participants Reporting Adverse Events of Special Interest (AESI)
时间窗: From first open-label dose (Day 1) up to open-label Week 32 (8 weeks after last dose)
An AESI is one of scientific and medical concern specific to the product, for which ongoing monitoring and rapid communication by investigator to sponsor can be appropriate. A summary of protocol defined AESIs include malignant neoplasms including and excluding non-melanoma skin cancer (NMSC), post-infusion systemic reactions (PISR), all infections of special interest (opportunistic infections \[OI\], Herpes Zoster \[HZ\], tuberculosis \[TB\], and sepsis), depression (including mood disorders and anxiety)/suicide/self-injury and deaths.
Double-blind Period: Percentage of Participants With Primary Efficacy Renal Response (PERR) at Week 104
时间窗: Week 104
PERR is defined as urinary protein creatinine ratio \<=0.7, estimated glomerular filtration rate (eGRF) was not more than 20 percent (%) below the pre-flare value or \>=60 milliliters per minute per 1.73 square meter (mL/min/1.73m\^2) and was not a treatment failure. Analysis was performed using a logistic regression model for the comparison between Belimumab and Placebo with covariates treatment group, induction regimen (CYC vs. MMF), race (Black vs. Non-Black), Baseline urine protein-creatinine ratio (uPCR), and Baseline eGFR. Modified Intent-to-treat (mITT) Population consisted of all randomized participants who received at least one dose of study treatment and were not excluded due to Good Clinical Practice (GCP) non-compliance. Percentage of participants with PERR at Week 104 has been presented.
Open-label Period: Number of Participants Reporting Adverse Events (AEs) and Serious AEs (SAEs)
时间窗: From first open-label dose (Day 1) up to open-label Week 32 (8 weeks after last dose)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with AEs and SAEs have been reported.
次要结局
- Double-blind Period: Percentage of Participants With Complete Renal Response (CRR) at Week 104(Week 104)
- Double-blind Period: Number of Participants With Time to Death or Renal Related Event(Up to Week 104)
- Double-blind Period: Number of Participants Reporting On-treatment AEs and SAEs(Up to Week 104)
- Double-blind Period: Percentage of Participants With PERR at Week 52(Week 52)
- Double-blind Period: Percentage of Participants With Ordinal Renal Response (ORR) at Week 104(Week 104)
- Double-blind Period: Number of Participants Reporting AESI(Up to Week 104)