A Phase 2, Randomized, Double-Blind, Multicenter Study Evaluating the Safety and Efficacy of Filgotinib and GS-9876 in Subjects With Lupus Membranous Nephropathy (LMN)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 7
- 主要终点
- Percent Change in Urine Protein From Baseline (Day 1) to Week 16
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of filgotinib and lanraplenib (previously GS-9876) in adults with lupus membranous nephropathy (LMN).
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, Investigator)
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
- •Kidney biopsy within the 36 months prior to screening with a histologic diagnosis of LMN (International Society of Nephrology [ISN] and the Renal Pathology Society [RPS] 2003 classification of lupus nephritis), either Class V alone, or Class V in combination with Class II.
- •Urine protein excretion ≥ 1.5 grams per day
- •Estimated glomerular filtration rate (eGFR) ≥ 40 mg/min/1.73m^2 based on the modification of diet in renal disease (MDRD) formulation at screening
- •No evidence of active or latent tuberculosis (TB) as assessed during screening
排除标准
- •Prior treatments as follows:
- •Previous treatment with a janus kinase (JAK) inhibitor within 3 months of Day 1
- •Use of rituximab or other selective B lymphocyte depleting agents (including experimental agents) within 6 months of Day
- •Enrollment is permitted if the last dose was given > 6 months and CD19-positive B cells are detectable at Screening.
- •Use of any concomitant prohibited medications as described in the protocol
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Lanraplenib 30 mg
Participants receive lanraplenib 30 mg tablet + filgotinib placebo tablet orally once daily for 16 weeks in Blinded Treatment Phase. Participants who achieve ≥ 35% reduction in urinary protein excretion from baseline continue to receive same blinded study treatment for additional 16 weeks. Participants who did not achieve a ≥ 35% reduction in urinary protein excretion will switch treatment.
After 32 weeks of blinded treatment, participants who have ≥ 35% reduction in urinary protein excretion from baseline continue their assigned blinded treatment for additional 20 weeks in Extended Blinded Treatment Phase.
干预措施: Lanraplenib (Drug)
Lanraplenib 30 mg
Participants receive lanraplenib 30 mg tablet + filgotinib placebo tablet orally once daily for 16 weeks in Blinded Treatment Phase. Participants who achieve ≥ 35% reduction in urinary protein excretion from baseline continue to receive same blinded study treatment for additional 16 weeks. Participants who did not achieve a ≥ 35% reduction in urinary protein excretion will switch treatment.
After 32 weeks of blinded treatment, participants who have ≥ 35% reduction in urinary protein excretion from baseline continue their assigned blinded treatment for additional 20 weeks in Extended Blinded Treatment Phase.
干预措施: Filgotinib placebo (Drug)
Filgotinib 200 mg
Participants receive filgotinib 200 mg tablet + lanraplenib placebo tablet orally once daily for 16 weeks in Blinded Treatment Phase. Participants who achieve ≥ 35% reduction in urinary protein excretion from baseline continue to receive same blinded study treatment for additional 16 weeks. Participants who did not achieve a ≥ 35% reduction in urinary protein excretion will switch treatment.
After 32 weeks of blinded treatment, participants who have ≥ 35% reduction in urinary protein excretion from baseline continue their assigned blinded treatment for additional 20 weeks in Extended Blinded Treatment Phase.
干预措施: Filgotinib (Drug)
Filgotinib 200 mg
Participants receive filgotinib 200 mg tablet + lanraplenib placebo tablet orally once daily for 16 weeks in Blinded Treatment Phase. Participants who achieve ≥ 35% reduction in urinary protein excretion from baseline continue to receive same blinded study treatment for additional 16 weeks. Participants who did not achieve a ≥ 35% reduction in urinary protein excretion will switch treatment.
After 32 weeks of blinded treatment, participants who have ≥ 35% reduction in urinary protein excretion from baseline continue their assigned blinded treatment for additional 20 weeks in Extended Blinded Treatment Phase.
干预措施: Lanraplenib placebo (Drug)
Lanraplenib 30 mg to Filgotinib 200 mg
At Week 16, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from baseline to Week 16 switch treatment and receive filgotinib 200 mg + lanraplenib placebo for additional 16 weeks.
At Week 32, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from Week 16 to Week 32 can continue whichever treatment that lead to the greatest reduction in urinary protein excretion, or either treatment per investigator's discretion for additional 20 weeks in Extended Blinded Treatment Phase.
干预措施: Filgotinib (Drug)
Lanraplenib 30 mg to Filgotinib 200 mg
At Week 16, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from baseline to Week 16 switch treatment and receive filgotinib 200 mg + lanraplenib placebo for additional 16 weeks.
At Week 32, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from Week 16 to Week 32 can continue whichever treatment that lead to the greatest reduction in urinary protein excretion, or either treatment per investigator's discretion for additional 20 weeks in Extended Blinded Treatment Phase.
干预措施: Lanraplenib placebo (Drug)
Filgotinib 200 mg to Lanraplenib 30 mg
At Week 16, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from baseline to Week 16 switch treatment and receive lanraplenib 30 mg + filgotinib placebo for additional 16 weeks.
At Week 32, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from Week 16 to Week 32 can continue whichever treatment that lead to the greatest reduction in urinary protein excretion, or either treatment per investigator's discretion for additional 20 weeks in Extended Blinded Treatment Phase.
干预措施: Lanraplenib (Drug)
Filgotinib 200 mg to Lanraplenib 30 mg
At Week 16, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from baseline to Week 16 switch treatment and receive lanraplenib 30 mg + filgotinib placebo for additional 16 weeks.
At Week 32, participants who do not achieve a ≥ 35% reduction in urinary protein excretion from Week 16 to Week 32 can continue whichever treatment that lead to the greatest reduction in urinary protein excretion, or either treatment per investigator's discretion for additional 20 weeks in Extended Blinded Treatment Phase.
干预措施: Filgotinib placebo (Drug)
结局指标
主要结局
Percent Change in Urine Protein From Baseline (Day 1) to Week 16
时间窗: Baseline; Week 16
Urine protein was assessed by urinary protein excretion during a 24-hour urine collection.
次要结局
- Change From Baseline (Day 1) in Urine Protein at Week 16(Baseline; Week 16)
- Change From Baseline (Day 1) in Estimated Glomerular Filtration Rate (eGFR) at Week 16(Baseline; Week 16)
- Change From Baseline (Day 1) in Urine Protein Creatinine Ratio (UPCR) at Week 16(Baseline; Week 16)
- Percentage of Participants With Partial Remission at Week 16(Week 16)
- Percentage of Participants With Complete Remission at Week 16(Week 16)