A Multi-center, Randomized, Placebo-Controlled Trial to Evaluate the Safety, Efficacy, and Pharmacokinetics of Belimumab, a Human Monoclonal Anti-BLyS Antibody, Plus Standard Therapy in Pediatric Patients With Systemic Lupus Erythematosus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 93
- 试验地点
- 32
- 主要终点
- Percentage of Participants With SLE Responder Index (SRI) Response at Week 52
研究概览
简要总结
This is a multi-center study to evaluate the safety, pharmacokinetics, and efficacy of belimumab intravenous (IV) in pediatric patients 5 to 17 years of age with active systemic lupus erythematosus
详细描述
This is a multi-center study to evaluate the safety, pharmacokinetics, and efficacy of belimumab intravenous (IV) in pediatric patients 5 to 17 years of age with active systemic lupus erythematosus (SELENA SLEDAI score ≥ 6). The study will consist of three phases: a 52-week randomized, placebo-controlled, double-blind phase; a long term open label continuation phase; and a long term safety follow up phase. The long term open label continuation and safety follow up periods will continue for at least 5 years and possibly up to 10 years from a subject's initial treatment with belimumab. Enrolment will be staggered by age cohorts to allow safety and PK interim analyses. Subjects will be randomized to belimumab 10mg/kg or placebo IV monthly dosing while continuing to receive background standard therapy throughout the study. An independent data monitoring committee (IDMC) will monitor the study as it progresses.
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
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •5 years to 17 years of age at enrollment
- •Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria.
- •Have active SLE disease (SELENA SLEDAI score ≥ 6).
- •Have positive anti-nuclear antibody (ANA) test results.
- •Are on a stable SLE treatment regimen at a fixed dose for a period of at least 30 days prior to Day
- •Females of childbearing age are willing to use appropriate contraception
- •Subject age appropriate assent and parent or legal guardian informed consent to participate
排除标准
- •Pregnant or nursing.
- •Have received treatment with belimumab (BENLYSTA®) at any time. (BENLYSTA® is a registered trademark of the GSK group of companies.)
- •Treatment with any B cell targeted therapy (for example, rituximab) or an investigational biological agent in the past year.
- •Have received anti-TNF therapy; Interleukin-1 receptor antagonist; IVIG; or plasmapheresis within 90 days of Day
- •Have received high dose prednisone or equivalent (>1.5mg/kg/day) within 60 days of baseline.
- •Have received intravenous (IV) cyclophosphamide within 60 days of Day
- •Have received any new immunosuppressive/immunomodulatory agent, anti-malarial agent within 60 days of baseline.
- •Have severe lupus kidney disease.
- •Have active central nervous system (CNS) lupus.
- •Have had a major organ transplant.
- •Have significant unstable or uncontrolled acute or chronic diseases or conditions not due to SLE.
- •Have a planned surgical procedure.
- •History of malignant neoplasm within the last 5 years.
- •Have required management of acute or chronic infections in the past 60 days.
- •Have current drug or alcohol abuse or dependence.
- •Have a historically positive test, or test positive at screening for HIV, Hepatitis B, or Hepatitis C.
- •Have an IgA deficiency.
- •Have severe laboratory abnormalities.
- •Have had anaphylactic reaction to X-ray contrast agents or biologic agents.
- •Suicidal behavior or ideation.
- •Children in Care(CiC): a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation.
研究组 & 干预措施
Part A: Placebo
Participants received saline infusion (placebo) intravenously monthly for 48 weeks on a background of standard of care.
干预措施: Placebo (Other)
Part B: Open-Label Belimumab
Participants who entered Part B after completing 48 weeks of belimumab or placebo on a background of standard of care and the Week 52 assessments in Part A, received 10 mg/kg belimumab intravenously monthly up to 10 years from the first administration of belimumab.
干预措施: Belimumab 10 mg/kg (Drug)
Part C: Safety Follow-up Phase
Participants who entered Part C after discontinuing study intervention in Part A or Part B were included in this arm.
Part A: Belimumab 10 mg/kg
Participants received 10 milligrams per kilograms (mg/kg) reconstituted solution intravenously monthly for 48 weeks on a background of standard of care.
干预措施: Belimumab 10 mg/kg (Drug)
结局指标
主要结局
Percentage of Participants With SLE Responder Index (SRI) Response at Week 52
时间窗: Week 52
SRI response is defined as \>=4 point reduction, from Baseline in safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score, no worsening (increase of \<0.30 points from Baseline) in physician's global assessment (PGA) and no new British Isles Lupus Assessment Group of SLE clinics (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with Baseline. Analysis was performed using a logistic regression model for the comparison between belimumab and placebo with covariates treatment group, Baseline SELENA SLEDAI score (\<=12 vs. \>=13). Percentage of participants with SRI response at Week 52 of Part A were reported. Intent-to-Treat Population comprised of all participants who were randomized and treated with at least one dose of study agent in Part A. One participant had missing data at Baseline and therefore, could not be included in the analysis.
次要结局
- Percent Change From Baseline in ParentGA at Week 52(Baseline (Day 0) and Week 52)
- Percent Change From Baseline in PGA at Week 52(Baseline (Day 0) and Week 52)
- Percentage of Participants With a Sustained SRI Response(Up to 52 weeks)
- Area Under Curve of Belimumab at Steady State (AUC, ss)(28-days dosing interval at steady state)
- Percentage of Participants Meeting Pediatric Rheumatology International Trials Organization (PRINTO)/ American College of Rheumatology (ACR) Juvenile SLE Response Evaluation Criteria for Improvement in Juvenile SLE at Week 52 Using Definition 1 and 2(Week 52)
- Percent Change From Baseline in PedsQL Physical Functioning Domain Score at Week 52(Baseline (Day 0) and Week 52)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 60 weeks)
- Percent Change From Baseline in SELENA SLEDAI at Week 52(Baseline (Day 0) and Week 52)
- Percent Change From Baseline in Proteinuria at Week 52(Baseline (Day 0) and Week 52)
- Percentage of Participants With a Sustained ParentGA Response(Up to 52 weeks)
- Maximum Concentration at Steady State (Cmax, ss) and Minimum Concentration at Steady State (Cmin, ss)(28-days dosing interval at steady state)