A Phase 2b, Randomized, Controlled Double-blind, Multicenter Study Comparing the Efficacy and Safety of Zetomipzomib (KZR-616) 30 mg or 60 mg With Placebo in Patients With Active Lupus Nephritis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 84
- 试验地点
- 49
- 主要终点
- Proportion of Patients Achieving Complete Renal Response
研究概览
简要总结
The purpose of this study was to assess the efficacy and safety of zetomipzomib (30 mg or 60 mg) compared with placebo in achieving renal response after 52 weeks of treatment in patients with active lupus nephritis (LN).
详细描述
This study aimed to investigate whether zetomipzomib, added to standard of care treatment in patients with active LN, was able to reduce disease activity over a treatment period of 52 weeks. The background standard of care therapy was mycophenolate mofetil (MMF) and initial optional treatment with IV methylprednisolone, followed by a tapering course of oral corticosteroids.
Patients were required to have a diagnosis of LN according to established diagnostic criteria and clinical and biopsy features suggestive of active nephritis.
Patients were randomized in a 2:1 ratio to receive either zetomipzomib (30 mg or 60 mg) or placebo administered as a subcutaneous injection once weekly for 52 weeks, followed by a 4-week safety follow-up period. Efficacy was to be assessed by measuring the level of proteinuria (as measured by urine protein to creatinine ratio [UPCR]) and estimated glomerular filtration rate (eGFR) as compared to current standard of care treatment. Safety was also assessed throughout the study to ensure an acceptable safety profile.
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
- •Body mass index of ≥18 kg/m^2
- •eGFR ≥30 mL/min/1.73 m^2
- •Unequivocally positive ANA test result and/or a positive anti-dsDNA serum antibody test
- •Diagnosis of LN according to 2003 or 2018 ISN/RPS criteria and confirmed by renal biopsy performed within 12 months prior to Screening.
- •UPCR ≥1.0 (Class III/IV +/-V) or UPCR ≥2.0 (Class V)
- •Adequate hematologic, hepatic, and renal function
排除标准
- •Current or medical history of:
- •Central nervous system manifestations of SLE
- •Overlapping autoimmune condition that may affect study assessments/outcomes
- •Antiphospholipid syndrome with history of thromboembolic event of within the 52 weeks prior to Screening
- •Thrombocytopenia or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies (i.e., plasmapheresis or acute blood or platelet transfusions
- •Solid organ transplant or planned transplant during study
- •Malignancy of any type, with exceptions for non-melanoma skin cancers and certain cancers >5 years ago
- •Has received dialysis within the 52 weeks prior to Screening
- •Positive test at Screening for HIV, hepatitis B/C
- •Known intolerance to MMF or equivalent and corticosteroids
研究组 & 干预措施
zetomipzomib 30 mg + standard-of-care
Participants randomized to be treated with initial 30 mg dose of zetomipzomib, followed by weekly doses of 30 mg zetomipzomib through the treatment period in addition to background standard of care therapy.
干预措施: zetomipzomib (Drug)
zetomipzomib 60 mg + standard-of-care
Participants randomized to be treated with initial 30 mg dose of zetomipzomib, followed by weekly doses of 60 mg zetomipzomib through the treatment period in addition to background standard of care therapy.
干预措施: zetomipzomib (Drug)
placebo + standard-of-care
Participants randomized to be treated with initial 30 mg dose of placebo, followed by weekly doses (30 mg or 60 mg) of placebo through the treatment period in addition to background standard of care therapy.
干预措施: placebo (Drug)
结局指标
主要结局
Proportion of Patients Achieving Complete Renal Response
时间窗: Week 37
Proportion of patients achieving complete renal response (CRR), defined as: * A UPCR ≤0.5 in one 24-hour urine sample (for primary endpoint and Week 53) or 2 consecutive first morning void urine samples (for all other time points) * An eGFR ≥60 mL/min/1.73 m\^2 or no confirmed decrease of \>20% from Baseline eGFR.
次要结局
- Proportion of Patients Achieving Partial Renal Response (PRR)(Week 25 and Week 37)
- Proportion of Patients Achieving Complete Renal Response(Week 25)
- Change in UPCR(Week 13, Week 25, and Week 37)
- Time to Complete Renal Response and Partial Renal Response(Baseline through Week 37)
- Proportion of Patients With UPCR ≤0.5(Week 13, Week 25, and Week 37)
- Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K)(Week 13, Week 25, and Week 37)