Study to Evaluate the Safety and Efficacy of Filgotinib and Lanraplenib in Adults With Lupus Membranous Nephropathy (LMN)
Phase 2
Completed
- Conditions
- Lupus Membranous Nephropathy
- Interventions
- Registration Number
- NCT03285711
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 9
Inclusion Criteria
- 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
Key
Exclusion Criteria
-
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 1. 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lanraplenib 30 mg to Filgotinib 200 mg Filgotinib 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. Lanraplenib 30 mg Filgotinib placebo 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. Filgotinib 200 mg Lanraplenib placebo 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. Filgotinib 200 mg to Lanraplenib 30 mg Filgotinib placebo 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. Lanraplenib 30 mg to Filgotinib 200 mg Lanraplenib placebo 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. Filgotinib 200 mg Filgotinib 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. Lanraplenib 30 mg Lanraplenib 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. Filgotinib 200 mg to Lanraplenib 30 mg Lanraplenib 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.
- Primary Outcome Measures
Name Time Method Percent Change in Urine Protein From Baseline (Day 1) to Week 16 Baseline; Week 16 Urine protein was assessed by urinary protein excretion during a 24-hour urine collection.
- Secondary Outcome Measures
Name Time Method Change From Baseline (Day 1) in Urine Protein at Week 16 Baseline; Week 16 Urine protein was assessed by urinary protein excretion during a 24-hour urine collection.
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 UPCR was assessed by urine protein excretion during a 24-hour urine collection.
Percentage of Participants With Partial Remission at Week 16 Week 16 Partial Remission was defined as urine protein excretion below \< 3 g/day and urine protein excretion decrease by ≥ 50% among participants with baseline (Day 1) nephrotic range proteinuria \[urine protein excretion ≥ 3 g/day\]; or urine protein excretion decrease by ≥ 50% among participants with subnephrotic range proteinuria \[urine protein excretion \< 3 g/day\]).
Percentage of Participants With Complete Remission at Week 16 Week 16 Complete Remission was defined as urine protein excretion below 0.5 g/day, with no hematuria.
Trial Locations
- Locations (7)
University of Alabama at Birmingham (UAB)
🇺🇸Birmingham, Alabama, United States
Stanford University
🇺🇸Palo Alto, California, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Georgia Nephrology Research Institute
🇺🇸Lawrenceville, Georgia, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of North Carolina at Chapel Hill / UNC School of Medicine
🇺🇸Chapel Hill, North Carolina, United States