A Randomized, Controlled Double-blind Study Comparing the Efficacy and Safety of Voclosporin (23.7 mg Twice Daily) With Placebo in Achieving Renal Response in Subjects With Active Lupus Nephritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 358
- 试验地点
- 3
- 主要终点
- Number of Participants With Adjudicated Renal Response at Week 52
研究概览
简要总结
The purpose of this study is to assess the efficacy of voclosporin compared with placebo in achieving renal response after 52 weeks of therapy in subjects with active lupus nephritis.
详细描述
The aim of the current study is to investigate whether voclosporin, added to the standard of care treatment in active lupus nephritis (LN), is able to reduce disease activity over a treatment period of 52 weeks. The background therapy will be mycophenolate mofetil (MMF) and initial treatment with IV methylprednisolone, followed by a reducing course of oral corticosteroids. Subjects with active, flaring LN will be eligible to enter the study. They are required to have a diagnosis of LN according to established diagnostic criteria and clinical and biopsy features suggestive of active nephritis. Efficacy will be assessed by the ability of the drug combination to reduce the level of proteinuria (as measured by Urine Protein Creatinine Ratio (UPCR)) while demonstrating 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with evidence of active nephritis, defined as follows:
- •Kidney biopsy result within 2 years prior to screening indicating Class III, IV-S, IV-G (alone or in combination with Class V), or Class V LN with a doubling or greater increase of UPCR within the last 6 months to a minimum of ≥1.5 mg/mg for Class III/IV or to a minimum of ≥2 mg/mg for Class V at screening. Biopsy results over 6 months prior to screening must be reviewed with a medical monitor to confirm eligibility.
- •Kidney biopsy result within 6 months prior to screening indicating Class III, IV-S or IV-G (alone or in combination with Class V) LN with a UPCR of ≥1.5 mg/mg at screening.
- •Kidney biopsy result within 6 months prior to screening indicating Class V LN and a UPCR of ≥2 mg/mg at screening.
- •Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline.
排除标准
- •Estimated glomerular filtration rate (eGFR) of ≤45 mL/minute at screening.
- •Current or medical history of:
- •Congenital or acquired immunodeficiency.
- •In the opinion of the Investigator, clinically significant drug or alcohol abuse within 2 years prior to screening.
- •Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision.
- •Lymphoproliferative disease or previous total lymphoid irradiation.
- •Severe viral infection or known HIV infection.
- •Active tuberculosis (TB), or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid.
- •Other known clinically significant active medical conditions, such as:
- •Severe cardiovascular disease, liver dysfunction or chronic obstructive pulmonary disease or asthma requiring oral steroids or any other overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes.
研究组 & 干预措施
Placebo Oral Capsule
Voclosporin placebo, oral, 3 capsules twice daily (BID)
干预措施: Placebo Oral Capsule (Drug)
Voclosporin
oral, 23.7 mg twice daily (BID)
干预措施: Voclosporin (Drug)
结局指标
主要结局
Number of Participants With Adjudicated Renal Response at Week 52
时间窗: 52 Weeks
The primary efficacy endpoint was the number of subjects showing renal response at Week 52. Renal response was adjudicated based on blinded data by an independent Clinical Endpoints Committee based on meeting the following criteria * UPCR of ≤0.5 mg/mg \& * eGFR ≥60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of \>20% \& * Received no rescue medication for LN \& * Did not receive more than 10 mg prednisone for ≥3 consecutive days or for ≥7 days in total during Weeks 44 through 52, prior to assessment Note:To be disqualified from renal response, the subject had to fail both eGFR measures (i.e., confirmed eGFR \<60 mL/min/1.73 m2 \& confirmed \>20% drop from baseline) \& have an associated treatment-related or disease-related AE that impacted eGFR Withdrawals prior to Week 52 with insufficient Week 52 data to determine response were defined non responders. Subjects who discontinued study drug but continued to attend study visits had their data assessed for response
次要结局
- Time to Urine Protein Creatinine Ratio of ≤0.5 mg/mg (Number of Days)(52 Weeks)
- Number of Subjects With Partial Renal Response at Weeks 24 & 52(Weeks 24 and 52)
- Number of Subjects Achieving 50% Reduction in Urine Protein Creatinine Ratio(52 Weeks)
- Time to 50% Reduction in UPCR (Number of Days)(52 weeks)
- Change From Baseline in eGFR(Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.)
- Number of Subjects With Renal Response With Low Dose Steroids(Week 24 and Week 52)
- Number of Participants With Reduction in Urine Protein Creatinine Ratio to 0.5 mg/mg or Less(52 Weeks)
- Change From Baseline in UPCR(Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.)
- Number of Participants With Renal Response at Week 24(Week 24)
- Number of Subjects Achieving, and Remaining in, Renal Response (Urine Protein Creatinine Ratio ≤0.5 mg/mg)(Week 52)
- Duration of Renal Response (Number of Days)(Week 52)
- Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA - SLEDAI)(Week 24 and Week 52)
- Change From Baseline in Patient Reported Outcomes(Week 24 and Week 52)